Diabetes & Metabolism Journal

Original Articles

Pathophysiology
Recent Glycemia Is a Major Determinant of β-Cell Function in Type 2 Diabetes Mellitus: Ji Yoon Kim, Jiyoon Lee, Sin Gon Kim, Nam Hoon Kim; Received October 11, 2023 Accepted March 26, 2024 Published online June 17, 2024; DOI: https://doi.org/10.4093/dmj.2023.0359 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Progressive deterioration of β-cell function is a characteristic of type 2 diabetes mellitus (T2DM). We aimed to investigate the relative contributions of clinical factors to β-cell function in T2DM.
Methods
In a T2DM cohort of 470 adults (disease duration 0 to 41 years), β-cell function was estimated using insulinogenic index (IGI), disposition index (DI), oral disposition index (DIO), and homeostasis model assessment of β-cell function (HOMA-B) derived from a 75 g oral glucose tolerance test (OGTT). The relative contributions of age, sex, disease duration, body mass index, glycosylated hemoglobin (HbA1c) levels (at the time of the OGTT), area under the curve of HbA1c over time (HbA1c AUC), coefficient of variation in HbA1c (HbA1c CV), and antidiabetic agents use were compared by standardized regression coefficients. Longitudinal analyses of these indices were also performed.
Results
IGI, DI, DI_O, and HOMA-B declined over time (P<0.001 for all). Notably, HbA1c was the most significant factor affecting IGI, DI, DIO, and HOMA-B in the multivariable regression analysis. Compared with HbA1c ≥9%, DI was 1.9-, 2.5-, 3.7-, and 5.5-fold higher in HbA1c of 8%–<9%, 7%–<8%, 6%–<7%, and <6%, respectively, after adjusting for confounding factors (P<0.001). Conversely, β-cell function was not affected by the type or duration of antidiabetic agents, HbA1c AUC, or HbA1c CV. The trajectories of the IGI, DI, DIO, and HOMA-B mirrored those of HbA1c.
Conclusion
β-Cell function declines over time; however, it is flexible, being largely affected by recent glycemia in T2DM.

Metabolic Risk/Epidemiology
A Prospective 1-Year Follow-up of Glycemic Status and C-Peptide Levels of COVID-19 Survivors with Dysglycemia in Acute COVID-19 Infection: David Tak Wai Lui, Chi Ho Lee, Ying Wong, Carol Ho Yi Fong, Kimberly Hang Tsoi, Yu Cho Woo, Kathryn Choon Beng Tan; Diabetes Metab J. 2024;48(4):763-770. Published online March 11, 2024; DOI: https://doi.org/10.4093/dmj.2023.0175

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We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19.
Methods
COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes.
Results
Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m² to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group.
Conclusion
Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.

Review

Pathophysiology
Endoplasmic Reticulum Stress and Dysregulated Autophagy in Human Pancreatic Beta Cells: Seoil Moon, Hye Seung Jung; Diabetes Metab J. 2022;46(4):533-542. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0070

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Abstract PDF PubReader ePub

Pancreatic beta cell homeostasis is crucial for the synthesis and secretion of insulin; disruption of homeostasis causes diabetes, and is a treatment target. Adaptation to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR) and adequate regulation of autophagy, which are closely linked, play essential roles in this homeostasis. In diabetes, the UPR and autophagy are dysregulated, which leads to beta cell failure and death. Various studies have explored methods to preserve pancreatic beta cell function and mass by relieving ER stress and regulating autophagic activity. To promote clinical translation of these research results to potential therapeutics for diabetes, we summarize the current knowledge on ER stress and autophagy in human insulin-secreting cells.

Citations

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Interplay of skeletal muscle and adipose tissue: sarcopenic obesity
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Identification and analysis of type 2 diabetes-mellitus-associated autophagy-related genes
Kun Cui, Zhizheng Li
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Sestrin2 in diabetes and diabetic complications
Xiaodan Zhang, Zirui Luo, Jiahong Li, Yaxuan Lin, Yu Li, Wangen Li
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Asie Sadeghi, Maryam Niknam, Mohammad Amin Momeni-Moghaddam, Maryam Shabani, Hamid Aria, Alireza Bastin, Maryam Teimouri, Reza Meshkani, Hamed Akbari
European Journal of Medical Research.2023;[Epub] CrossRef
Beta cell lipotoxicity in the development of type 2 diabetes: the need for species-specific understanding
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Original Article

Basic Research
DA-1241, a Novel GPR119 Agonist, Improves Hyperglycaemia by Inhibiting Hepatic Gluconeogenesis and Enhancing Insulin Secretion in Diabetic Mice: Youjin Kim, Si Woo Lee, Hyejin Wang, Ryeong-Hyeon Kim, Hyun Ki Park, Hangkyu Lee, Eun Seok Kang; Diabetes Metab J. 2022;46(2):337-348. Published online January 21, 2022; DOI: https://doi.org/10.4093/dmj.2021.0056

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Abstract PDF Supplementary Material PubReader ePub

Background
We investigated the antidiabetic effects of DA-1241, a novel G protein-coupled receptor (GPR) 119 agonist, in vitro and in vivo.
Methods
DA-1241 was administrated to high-fat diet (HFD)-fed C57BL/6J mice for 12 weeks after hyperglycaemia developed. Oral/intraperitoneal glucose tolerance test and insulin tolerance test were performed. Serum insulin and glucagon-like peptide-1 (GLP-1) levels were measured during oral glucose tolerance test. Insulinoma cell line (INS-1E) cells and mouse islets were used to find whether DA-1241 directly stimulate insulin secretion in beta cell. HepG2 cells were used to evaluate the gluconeogenesis and autophagic process. Autophagic flux was evaluated by transfecting microtubule-associated protein 1 light chain 3-fused to green fluorescent protein and monomeric red fluorescent (mRFP-GFP-LC3) expression vector to HepG2 cells.
Results
Although DA-1241 treatment did not affect body weight gain and amount of food intake, fasting blood glucose level decreased along with increase in GLP-1 level. DA-1241 improved only oral glucose tolerance test and showed no effect in intraperitoneal glucose tolerance test. No significant effect was observed in insulin tolerance test. DA-1241 did not increase insulin secretion in INS-1E cell and mouse islets. DA-1241 reduced triglyceride content in the liver thereby improved fatty liver. Additionally, DA-1241 reduced gluconeogenic enzyme expression in HepG2 cells and mouse liver. DA-1241 reduced autophagic flow in HepG2 cells.
Conclusion
These findings suggested that DA-1241 augmented glucose-dependent insulin release via stimulation of GLP-1 secretion, and reduced hepatic gluconeogenesis, which might be associated with autophagic blockage, leading to improved glycaemic control.

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DA-1241, a Novel GPR119 Agonist, Improves Hyperglycaemia by Inhibiting Hepatic Gluconeogenesis and Enhancing Insulin Secretion in Diabetic Mice
Youjin Kim, Si Woo Lee, Hyejin Wang, Ryeong-Hyeon Kim, Hyun Ki Park, Hangkyu Lee, Eun Seok Kang
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Review

Technology/Device
Assessment of Insulin Secretion and Insulin Resistance in Human: So Young Park, Jean-François Gautier, Suk Chon; Diabetes Metab J. 2021;45(5):641-654. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0220

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Graphical Abstract Abstract PDF PubReader ePub

The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/ sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.

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Original Articles

Basic Research
Notch1 Has an Important Role in β-Cell Mass Determination and Development of Diabetes: Young Sil Eom, A-Ryeong Gwon, Kyung Min Kwak, Jin-Young Youn, Heekyoung Park, Kwang-Won Kim, Byung-Joon Kim; Diabetes Metab J. 2021;45(1):86-96. Published online February 26, 2020; DOI: https://doi.org/10.4093/dmj.2019.0160

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Background

Notch signaling pathway plays an important role in regulating pancreatic endocrine and exocrine cell fate during pancreas development. Notch signaling is also expressed in adult pancreas. There are few studies on the effect of Notch on adult pancreas. Here, we investigated the role of Notch in islet mass and glucose homeostasis in adult pancreas using Notch1 antisense transgenic (NAS).

Methods

Western blot analysis was performed for the liver of 8-week-old male NAS mice. We also conducted an intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test in 8-week-old male NAS mice and male C57BL/6 mice (control). Morphologic observation of pancreatic islet and β-cell was conducted in two groups. Insulin secretion capacity in islets was measured by glucose-stimulated insulin secretion (GSIS) and perifusion.

Results

NAS mice showed higher glucose levels and lower insulin secretion in IPGTT than the control mice. There was no significant difference in insulin resistance. Total islet and β-cell masses were decreased in NAS mice. The number of large islets (≥250 µm) decreased while that of small islets (<250 µm) increased. Reduced insulin secretion was observed in GSIS and perifusion. Neurogenin3, neurogenic differentiation, and MAF bZIP transcription factor A levels increased in NAS mice.

Conclusion

Our study provides that Notch1 inhibition decreased insulin secretion and decreased islet and β-cell masses. It is thought that Notch1 inhibition suppresses islet proliferation and induces differentiation of small islets. In conclusion, Notch signaling pathway may play an important role in β-cell mass determination and diabetes.

Citations

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Clinical Diabetes & Therapeutics
Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction?: Veronica Falcone, Grammata Kotzaeridi, Melanie Hanne Breil, Ingo Rosicky, Tina Stopp, Gülen Yerlikaya-Schatten, Michael Feichtinger, Wolfgang Eppel, Peter Husslein, Andrea Tura, Christian S. Göbl; Diabetes Metab J. 2019;43(6):785-793. Published online March 12, 2019; DOI: https://doi.org/10.4093/dmj.2018.0218

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Background

An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication.

Methods

A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15⁺⁶ weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery.

Results

Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%).

Conclusion

Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.

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Epidemiology
Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes between 2015 and 2016: Difference by Age and Body Mass Index: Kyoung Hwa Ha, Cheol Young Park, In Kyung Jeong, Hyun Jin Kim, Sang-Yong Kim, Won Jun Kim, Ji Sung Yoon, In Joo Kim, Dae Jung Kim, Sungrae Kim; Diabetes Metab J. 2018;42(2):137-146. Published online February 14, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.137

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Background

We evaluated the clinical characteristics of insulin resistance and β-cell dysfunction in newly diagnosed, drug-naive people with type 2 diabetes by analyzing nationwide cross-sectional data.

Methods

We collected the clinical data of 912 participants with newly diagnosed diabetes from 83 primary care clinics and hospitals nationwide from 2015 to 2016. The presence of insulin resistance and β-cell dysfunction was defined as a homeostatic model assessment of insulin resistance (HOMA-IR) value ≥2.5 and fasting C-peptide levels <1.70 ng/mL, respectively.

Results

A total of 75.1% and 22.6% of participants had insulin resistance and β-cell dysfunction, respectively. The proportion of participants with insulin resistance but no β-cell dysfunction increased, and the proportion of participants with β-cell dysfunction but no insulin resistance decreased as body mass index (BMI) increased. People diagnosed with diabetes before 40 years of age had significantly higher HOMA-IR and BMI than those diagnosed over 65 years of age (HOMA-IR, 5.0 vs. 3.0; BMI, 28.7 kg/m² vs. 25.1 kg/m²). However, the β-cell function indices were lower in people diagnosed before 40 years of age than in those diagnosed after 65 years of age (homeostatic model assessment of β-cell function, 39.3 vs. 64.9; insulinogenic index, 10.3 vs. 18.7; disposition index, 0.15 vs. 0.25).

Conclusion

We observed that the main pathogenic mechanism of type 2 diabetes is insulin resistance in participants with newly diagnosed type 2 diabetes. In addition, young adults with diabetes are more likely to have higher insulin resistance with obesity and have higher insulin secretory defect with severe hyperglycemia in the early period of diabetes than older populations.

Citations

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Comparison of β-Cell Function and Insulin Sensitivity Between Normal-Weight and Obese Chinese With Young-Onset Type 2 Diabetes
Yingnan Fan, Elaine Chow, Cadmon K.P. Lim, Yong Hou, Sandra T.F. Tsoi, Baoqi Fan, Eric S.H. Lau, Alice P.S. Kong, Ronald C.W. Ma, Hongjiang Wu, Juliana C.N. Chan, Andrea O.Y. Luk
Diabetes.2024; 73(6): 953. CrossRef
A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
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Davis Kibirige, Isaac Sekitoleko, Priscilla Balungi, William Lumu, Moffat J. Nyirenda
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Rising Incidence of Diabetes in Young Adults in South Korea: A National Cohort Study
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A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
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Diabetes & Metabolism Journal.2018; 42(2): 128. CrossRef
Response: Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes between 2015 and 2016: Difference by Age and Body Mass Index (Diabetes Metab J2018;42:137-46)
Kyoung Hwa Ha, Dae Jung Kim, Sungrae Kim
Diabetes & Metabolism Journal.2018; 42(3): 251. CrossRef
Letter: Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes between 2015 and 2016: Difference by Age and Body Mass Index (Diabetes Metab J 2018;42:137-46)
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Diabetes & Metabolism Journal.2018; 42(3): 249. CrossRef

Others
Comparison of the Usefulness of the Updated Homeostasis Model Assessment (HOMA2) with the Original HOMA1 in the Prediction of Type 2 Diabetes Mellitus in Koreans: Young Seok Song, You-Cheol Hwang, Hong-Yup Ahn, Cheol-Young Park; Diabetes Metab J. 2016;40(4):318-325. Published online May 27, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.4.318

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Background

The original homeostasis model assessment (HOMA1) and the updated HOMA model (HOMA2) have been used to evaluate insulin resistance (IR) and β-cell function, but little is known about the usefulness of HOMA2 for the prediction of diabetes in Koreans. The aim of this study was to demonstrate the usefulness of HOMA2 as a predictor of type 2 diabetes mellitus in Koreans without diabetes.

Methods

The study population consisted of 104,694 Koreans enrolled at a health checkup program and followed up from 2001 to 2012. Participants were divided into a normal glucose tolerance (NGT) group and a pre-diabetes group according to fasting glucose and glycosylated hemoglobin levels. Anthropometric and laboratory data were measured at the baseline checkup, and HOMA values were calculated at the baseline and follow-up checkups. The hazard ratios (HRs) of the HOMA1 and HOMA2 values and the prevalence of diabetes at follow-up were evaluated using a multivariable Cox proportional hazards model and Kaplan-Meier analysis.

Results

After adjusting for several diabetes risk factors, all of the HOMA values except 1/HOMA1-β and 1/HOMA2-β in the NGT group were significant predictors of the progression to diabetes. In the NGT group, there was no significant difference in HOMA1-IR (HR, 1.09; 95% confidence interval [CI], 1.04 to 1.14) and HOMA2-IR (HR, 1.11; 95% CI, 1.04 to 1.19). However, in the pre-diabetes group, 1/HOMA2-β was a more powerful marker (HR, 1.29; 95% CI, 1.26 to 1.31) than HOMA1-IR (HR, 1.23; 95% CI, 1.19 to 1.28) or 1/HOMA1-β (HR, 1.14; 95% CI, 1.12 to 1.16). In the non-diabetic group (NGT+pre-diabetes), 1/HOMA2-β was also a stronger predictor of diabetes (HR, 1.27; 95% CI, 1.25 to 1.29) than HOMA1-IR (HR, 1.14; 95% CI, 1.12 to 1.15) or 1/HOMA1-β (HR, 1.13; 95% CI, 1.11 to 1.14).

Conclusion

HOMA2 is more predictive than HOMA1 for the progression to diabetes in pre-diabetes or non-diabetic Koreans.

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Eun-Young Lee, Jae-Seung Yun, Seon-Ah Cha, Sun-Young Lim, Jin-Hee Lee, Yu-Bae Ahn, Kun-Ho Yoon, Seung-Hyun Ko
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Steven P. Hirsh, Marianne Pons, Steven V. Joyal, Andrew G. Swick
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Development of type 2 diabetes mellitus in people with intermediate hyperglycaemia
Bernd Richter, Bianca Hemmingsen, Maria-Inti Metzendorf, Yemisi Takwoingi
Cochrane Database of Systematic Reviews.2018;[Epub] CrossRef
The cut-off values of surrogate measures for insulin resistance in the Korean population according to the Korean Genome and Epidemiology Study (KOGES)
Bongyoung Kim, Hyun Young Choi, Wonhee Kim, Chiwon Ahn, Juncheol Lee, Jae Guk Kim, Jihoon Kim, Hyungoo Shin, Jae Myung Yu, Shinje Moon, Taulant Muka
PLOS ONE.2018; 13(11): e0206994. CrossRef
Testing for HbA1c, in addition to the oral glucose tolerance test, in screening for abnormal glucose regulation helps to reveal patients with early β-cell function impairment
Yu-Hsuan Li, Wayne Huey-Herng Sheu, Wen-Jane Lee, I-Te Lee, Shih-Yi Lin, Wen-Lieng Lee, Kae-Woei Liang, Jun-Sing Wang
Clinical Chemistry and Laboratory Medicine (CCLM).2018; 56(8): 1345. CrossRef
Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance
Sikandar Hayat Khan, Farah Sobia, Najmusaqib Khan Niazi, Syed Mohsin Manzoor, Nadeem Fazal, Fowad Ahmad
Diabetology & Metabolic Syndrome.2018;[Epub] CrossRef
Pancreatic β-Cell Function and Prognosis of Nondiabetic Patients With Ischemic Stroke
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Association of serum pancreatic derived factor ( PANDER) with beta-cell dysfunction in type 2 diabetes mellitus
Miral M. Shehata, Mohamed M. Kamal, Mohamed H. El-Hefnawy, Hala O. EL-Mesallamy
Journal of Diabetes and its Complications.2017; 31(4): 748. CrossRef

The Insulin Resistance but Not the Insulin Secretion Parameters Have Changed in the Korean Population during the Last Decade: Hae Kyung Yang, Jin Hee Lee, In-Young Choi, Hyuk Sang Kwon, Jeong Ah Shin, Seung Hee Jeong, Seung-Hwan Lee, Jae Hyoung Cho, Ho Young Son, Kun Ho Yoon; Diabetes Metab J. 2015;39(2):117-125. Published online April 20, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.2.117

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Abstract PDF PubReader

Background

This study aimed to compare the patterns of insulin secretion and resistance between Korean subjects in the 1990s and 2000s.

Methods

Insulin secretion and resistance indices were calculated from subjects who underwent 75-g oral glucose tolerance tests in the year 1997 to 1999 and 2007 to 2011 at the Seoul St. Mary's Hospital, Korea.

Results

A total of 578 subjects from the 1990s (mean age, 48.5 years) and 504 subjects from the 2000s (mean age, 50.2 years) were enrolled. Compared with the subjects from the 1990s, those from the 2000s exhibited increased insulin resistance (increased homeostatic model assessment for insulin resistance), and reduced insulin sensitivity (reduced Matsuda index and quantitative insulin sensitivity check index), regardless of their glucose tolerance status. However, insulinogenic index did not reveal significant differences between the 2 decades in subjects with or without diabetes. A distinct relationship was confirmed between Matsuda index and total area under the curve (insulin/glucose) in each glucose tolerance group. The mean product of the Matsuda index and the total area under the curve (insulin/glucose) as well as the oral disposition index, was lower in subjects with normal glucose tolerance from the 2000s than in those from the 1990s.

Conclusion

After rapid economic growth and changes in lifestyle patterns, insulin resistance has worsened across the glucose tolerance status; however, the insulin secretory function remained unchanged, which resulted in an increase in the susceptibility to the development of type 2 diabetes mellitus among Korean subjects without diabetes. We could not rule out the potential selection bias and therefore, further studies in general Korean population are needed.

Citations

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Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
A Randomized Crossover Study Comparing the Effects of Diabetes-Specific Formula with Common Asian Breakfasts on Glycemic Control and Satiety in Adults with Type 2 Diabetes Mellitus
Sing Teang Kong, Dieu Thi Thu Huynh, Weerachai Srivanichakorn, Weerapan Khovidhunkit, Chaiwat Washirasaksiri, Tullaya Sitasuwan, Chengrong Huang, Swapnil Paunikar, Menaka Yalawar, Siew Ling Tey
Diabetology.2024; 5(4): 447. CrossRef
Longitudinal Changes in Insulin Resistance, Beta-Cell Function and Glucose Regulation Status in Prediabetes
Chul-Hee Kim, Hong-Kyu Kim, Eun-Hee Kim, Sung-Jin Bae, Jaewon Choe, Joong-Yeol Park
The American Journal of the Medical Sciences.2018; 355(1): 54. CrossRef
Association of serum 25-hydroxyvitamin D and diabetes-related factors in Korean adults without diabetes: The Fifth Korea National Health and Nutrition Examination Survey 2010–2012
Hyunah Kim, Hyunyong Lee, Hyeon Woo Yim, Hun-Sung Kim
Primary Care Diabetes.2018; 12(1): 59. CrossRef
Long‐term effects on glycaemic control and β‐cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial
Suk Chon, Sang Youl Rhee, Kyu Jeung Ahn, Sei Hyun Baik, Yongsoo Park, Moon Suk Nam, Kwan Woo Lee, Soon Jib Yoo, Gwanpyo Koh, Dae Ho Lee, Young Seol Kim, Jeong‐Taek Woo
Diabetes, Obesity and Metabolism.2018; 20(5): 1121. CrossRef
Four Plasma Glucose and Insulin Responses to a 75 g OGTT in Healthy Young Japanese Women
Kei Takahashi, Hidetaka Nakamura, Hiroshi Sato, Hideto Matsuda, Kazuo Takada, Tomiko Tsuji
Journal of Diabetes Research.2018; 2018: 1. CrossRef
Comparison of insulin intensification strategies with insulin lispro low mixture twice daily versus basal insulin glargine and prandial insulin lispro once daily in East Asian and Caucasian patients with type 2 diabetes mellitus
In‐Kyung Jeong, Choon Hee Chung, Zhiguang Zhou, Jeong Hee Han, Ran Duan, Diana M. Edralin, Angel Rodriguez
Journal of Diabetes.2017; 9(4): 396. CrossRef
Insulin Secretory Capacity and Insulin Resistance in Korean Type 2 Diabetes Mellitus Patients
Jong-Dai Kim, Won-Young Lee
Endocrinology and Metabolism.2016; 31(3): 354. CrossRef
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Min-Ji AHN, Sin-Gu JEONG, Goang-Won CHO
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Urinary N-acetyl-β-D-glucosaminidase, an early marker of diabetic kidney disease, might reflect glucose excursion in patients with type 2 diabetes
So Ra Kim, Yong-ho Lee, Sang-Guk Lee, Eun Seok Kang, Bong-Soo Cha, Jeong-Ho Kim, Byung-Wan Lee
Medicine.2016; 95(27): e4114. CrossRef

Hexane Extract of Orthosiphon stamineus Induces Insulin Expression and Prevents Glucotoxicity in INS-1 Cells: Hae-Jung Lee, Yoon-Jung Choi, So-Young Park, Jong-Yeon Kim, Kyu-Chang Won, Jong-Keun Son, Yong-Woon Kim; Diabetes Metab J. 2015;39(1):51-58. Published online February 16, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.1.51

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Background

Hyperglycemia, a characteristic feature of diabetes, induces glucotoxicity in pancreatic β-cells, resulting in further impairment of insulin secretion and worsening glycemic control. Thus, preservation of insulin secretory capacity is essential for the management of type 2 diabetes. In this study, we evaluated the ability of an Orthosiphon stamineus (OS) extract to prevent glucotoxicity in insulin-producing cells.

Methods

We measured insulin mRNA expression and glucose-stimulated insulin secretion (GSIS) in OS-treated INS-1 cells after exposure to a high glucose (HG; 30 mM) concentration.

Results

The hexane extract of OS elevated mRNA expression of insulin as well as pancreatic and duodenal homeobox-1 of INS-1 cells in a dose-dependent manner. The hexane OS extract also increased the levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) in a concentration-dependent manner. Additionally, Akt phosphorylation was elevated by treatment with 100 and 200 µmol of the hexane OS extract. Three days of HG exposure suppressed insulin mRNA expression and GSIS; these expressions were restored by treatment with the hexane OS extract. HG elevated peroxide levels in the INS-1 cells. These levels were unaffected by OS treatment under both normal and hyperglycemic conditions.

Conclusion

Our results suggested that the hexane extract of OS elevates insulin mRNA expression and prevents glucotoxicity induced by a 3-day treatment with HG. This was associated with the activation of PI-3K and Akt.

Citations

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An Updated Review of Ethnobotany, Ethnopharmacology, Phytochemistry and Pharmacological Activities of Orthosiphon stamineus Benth
Anandarajagopal Kalusalingam, Dania Najiha Hasnu, Abdullah Khan, Ching Siang Tan, Bama Menon, Venkateshan Narayanan, Khang Wen Goh, Asmuni Mohd Ikmal, Noraini Talip, Poonguzhali Subramanian, Long Chiau Ming
Malaysian Applied Biology.2024; 53(1): 1. CrossRef
Scopoletin protects INS-1 pancreatic β cells from glucotoxicity by reducing oxidative stress and apoptosis
Jae Eun Park, Ji Sook Han
Toxicology in Vitro.2023; 93: 105665. CrossRef
A Systematic Review of Orthosiphon stamineus Benth. in the Treatment of Diabetes and Its Complications
Qirou Wang, Jia Wang, Nannan Li, Junyu Liu, Jingna Zhou, Pengwei Zhuang, Haixia Chen
Molecules.2022; 27(2): 444. CrossRef
Comprehensive chemical and metabolic profiling of anti‐hyperglycemic active fraction from Clerodendranthi Spicati Herba
Yun Luo, Yue Liu, Quan Wen, Yulin Feng, Ting Tan
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Short-Term Protocols to Obtain Insulin-Producing Cells from Rat Adipose Tissue: Signaling Pathways and In Vivo Effect
Krista Minéia Wartchow, Letícia Rodrigues, Lucas Zingano Suardi, Barbara Carolina Federhen, Nicholas Guerini Selistre, Carlos-Alberto Gonçalves, Patrícia Sesterheim
International Journal of Molecular Sciences.2019; 20(10): 2458. CrossRef
Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants
Chintha Lankatillake, Tien Huynh, Daniel A. Dias
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50% Ethanol extract of Orthosiphon stamineus modulates genotoxicity and clastogenicity induced by mitomycin C
Dhamraa Waleed Al-dualimi, Aman Shah Abdul Majid, Sarah Furqan Faisal Al-Shimary, Amal Aziz Al-Saadi, Raghdaa Al Zarzour, Muhammad Asif, Chern Ein Oon, Amin Malik Shah Abdul Majid
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Can Tea Extracts Exert a Protective Effect Against Diabetes by Reducing Oxidative Stress and Decreasing Glucotoxicity in Pancreatic β-Cells?
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Impact of Serum Triglyceride and High Density Lipoprotein Cholesterol Levels on Early-Phase Insulin Secretion in Normoglycemic and Prediabetic Subjects: Masanori Shimodaira, Tomohiro Niwa, Koji Nakajima, Mutsuhiro Kobayashi, Norinao Hanyu, Tomohiro Nakayama; Diabetes Metab J. 2014;38(4):294-301. Published online August 20, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.4.294

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Abstract PDF PubReader

Background

Increased triglycerides (TGs) and decreased high density lipoprotein cholesterol (HDL-C) levels are established as diabetic risks for nondiabetic subjects. The aim of this study was to investigate the relationship among TG, HDL-C, TG/HDL-C ratio, and early-phase insulin secretion in normoglycemic and prediabetic subjects.

Methods

We evaluated 663 Japanese subjects who underwent the 75-g oral glucose tolerance test. On the basis of these results, the subjects were divided into four groups: those with normal glucose tolerance (NGT; n=341), isolated impaired fasting glucose (i-IFG; n=211), isolated impaired glucose tolerance (i-IGT; n=71), and combined IFG and IGT (IFG+IGT; n=40). Insulin secretion was estimated by the insulinogenic index (IGI) (Δinsulin/Δglucose [30 to 0 minutes]) and disposition index (DI) (IGI/homeostasis model assessment of insulin resistance).

Results

In prediabetic subjects (i-IFG, i-IGT, and IFG+IGT), linear regression analyses revealed that IGI and DI were positively correlated with HDL-C levels. Moreover, in subjects with i-IGT and (IFG+IGT), but not with i-IFG, the indices of insulin secretion were negatively correlated with the log-transformed TG and TG/HDL-C ratio. In both the subjects with i-IGT, multivariate linear regression analyses revealed that DI was positively correlated with HDL-C and negatively with log-transformed TG and TG/HDL-C ratio. On the other hand, in subjects with NGT, there was no association between insulin secretion and lipid profiles.

Conclusion

These results revealed that serum TG and HDL-C levels have different impacts on early-phase insulin secretion on the basis of their glucose tolerance status.

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Sudan Wang, Xiaoyan Qian, Chao Shen, Qian Sun, Yang Jing, Bingyue Liu, Kexin Zhang, Mengyuan Li, Junrong Wang, Hui Zhou, Chen Dong
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Journal of Human Genetics.2023; 68(12): 835. CrossRef
Elevated triglyceride/high-density lipoprotein-cholesterol ratio as a risk factor for progression to prediabetes: a 5-year retrospective cohort study in Japan
Masanori Shimodaira, Yu Minemura, Tomohiro Nakayama
Journal of Diabetes & Metabolic Disorders.2023; 23(1): 655. CrossRef
Association ofTG/HDLCratio trajectory and risk of type 2 diabetes: A retrospective cohort study inChina
Yanyan Zhang, Pei Qin, Yanmei Lou, Ping Zhao, Xue Li, Ranran Qie, Xiaoyan Wu, Minghui Han, Shengbing Huang, Yang Zhao, Dechen Liu, Yuying Wu, Yang Li, Xingjin Yang, Yang Zhao, Yifei Feng, Changyi Wang, Jianping Ma, Xiaolin Peng, Hongen Chen, Dan Zhao, Sha
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Triglycerides/high-density lipoprotein cholesterol is a predictor similar to the triglyceride–glucose index for the diagnosis of metabolic syndrome using International Diabetes Federation criteria of insulin resistance in obese adolescents: a cross-sectio
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Comparison of Serum PCSK9 Levels in Subjects with Normoglycemia, Impaired Fasting Glucose, and Impaired Glucose Tolerance
Eugene Han, Nan Hee Cho, Seong-Su Moon, Hochan Cho
Endocrinology and Metabolism.2020; 35(2): 480. CrossRef
Triglycerides/glucose index is a useful surrogate marker of insulin resistance among adolescents
B Kang, Y Yang, E Y Lee, H K Yang, H-S Kim, S-Y Lim, J-H Lee, S-S Lee, B-K Suh, K-H Yoon
International Journal of Obesity.2017; 41(5): 789. CrossRef
The TyG index may predict the development of cardiovascular events
Laura Sánchez‐Íñigo, David Navarro‐González, Alejandro Fernández‐Montero, Juan Pastrana‐Delgado, Jose Alfredo Martínez
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TyG Index Change Is More Determinant for Forecasting Type 2 Diabetes Onset Than Weight Gain
David Navarro-González, Laura Sánchez-Íñigo, Alejandro Fernández-Montero, Juan Pastrana-Delgado, Jose Alfredo Martinez
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Comparative analysis of the efficacy of omega-3 fatty acids for hypertriglyceridaemia management in Korea
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Lipoproteins and β-Cell Functions: From Basic to Clinical Data
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Reviews

Neonatal Diabetes Caused by Activating Mutations in the Sulphonylurea Receptor: Peter Proks; Diabetes Metab J. 2013;37(3):157-164. Published online June 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.3.157

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Abstract PDF PubReader

Adenosine triphosphate (ATP)-sensitive potassium (K_ATP) channels in pancreatic β-cells play a crucial role in insulin secretion and glucose homeostasis. These channels are composed of two subunits: a pore-forming subunit (Kir6.2) and a regulatory subunit (sulphonylurea receptor-1). Recent studies identified large number of gain of function mutations in the regulatory subunit of the channel which cause neonatal diabetes. Majority of mutations cause neonatal diabetes alone, however some lead to a severe form of neonatal diabetes with associated neurological complications. This review focuses on the functional effects of these mutations as well as the implications for treatment.

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Pamela Bowman, Frances Mathews, Fabrizio Barbetti, Maggie H. Shepherd, Janine Sanchez, Barbara Piccini, Jacques Beltrand, Lisa R. Letourneau-Freiberg, Michel Polak, Siri Atma W. Greeley, Eamon Rawlins, Tarig Babiker, Nicholas J. Thomas, Elisa De Franco, S
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Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle
Shoichiro Horita, Tomoyuki Ono, Saul Gonzalez-Resines, Yuko Ono, Megumi Yamachi, Songji Zhao, Carmen Domene, Yuko Maejima, Kenju Shimomura
Scientific Reports.2021;[Epub] CrossRef
Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review
Meng Li, Xueyao Han, Linong Ji, Karim Gariani
Journal of Diabetes Research.2021; 2021: 1. CrossRef
Spacial models of malfunctioned protein complexes help to elucidate signal transduction critical for insulin release
Katarzyna Walczewska-Szewc, Wieslaw Nowak
Biosystems.2019; 177: 48. CrossRef
Cantu syndrome–associated SUR2 (ABCC9) mutations in distinct structural domains result in KATP channel gain-of-function by differential mechanisms
Conor McClenaghan, Alex Hanson, Monica Sala-Rabanal, Helen I. Roessler, Dragana Josifova, Dorothy K. Grange, Gijs van Haaften, Colin G. Nichols
Journal of Biological Chemistry.2018; 293(6): 2041. CrossRef
Hyperinsulinism-Causing Mutations Cause Multiple Molecular Defects in SUR1 NBD1
Claudia P. Alvarez, Marijana Stagljar, D. Ranjith Muhandiram, Voula Kanelis
Biochemistry.2017; 56(18): 2400. CrossRef
K_ATP Channel Mutations and Neonatal Diabetes
Kenju Shimomura, Yuko Maejima
Internal Medicine.2017; 56(18): 2387. CrossRef
Molecular action of sulphonylureas on KATP channels: a real partnership between drugs and nucleotides
Heidi de Wet, Peter Proks
Biochemical Society Transactions.2015; 43(5): 901. CrossRef
Successful development and use of a thermodynamic stability screen for optimizing the yield of nucleotide binding domains
Elvin D. de Araujo, Voula Kanelis
Protein Expression and Purification.2014; 103: 38. CrossRef
Reclasificación y transferencia de insulina a sulfonilureas en un paciente con mutación en KCNJ11 tras 15 años de tratamiento con insulina
Magdalena Capponi, Carmen Quirós, Ignacio Conget, Enric Esmatjes, Marga Giménez
Avances en Diabetología.2014; 30(4): 115. CrossRef

A Systematic Review of Oxidative Stress and Safety of Antioxidants in Diabetes: Focus on Islets and Their Defense: Udayakumar Karunakaran, Keun-Gyu Park; Diabetes Metab J. 2013;37(2):106-112. Published online April 16, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.2.106

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A growing body of evidence suggests that hyperglycemia-induced oxidative stress plays an important role in diabetic complications, especially β-cell dysfunction and failure. Under physiological conditions, reactive oxygen species serve as second messengers that facilitate signal transduction and gene expression in pancreatic β-cells. However, under pathological conditions, an imbalance in redox homeostasis leads to aberrant tissue damage and β-cell death due to a lack of antioxidant defense systems. Taking into account the vulnerability of islets to oxidative damage, induction of endogenous antioxidant enzymes or exogenous antioxidant administration has been proposed as a way to protect β-cells against diabetic insults. Here, we consider recent insights into how the redox response becomes deregulated under diabetic conditions, as well as the therapeutic benefits of antioxidants, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with β-cell failure.

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Validation of the traditional medicinal use of a Mexican endemic orchid (Prosthechea karwinskii) through UPLC-ESI-qTOF-MS/MS characterization of its bioactive compounds
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N-acetyl-L-cysteine ameliorates hepatocyte pyroptosis of dog type 1 diabetes mellitus via suppression of NLRP3/NF-κB pathway
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Vitamin D regulates insulin and ameliorates apoptosis and oxidative stress in pancreatic tissues of rats with streptozotocin-induced diabetes
Fatima El Zahra M. Fathi, Kadry M. Sadek, Asmaa F. Khafaga, Abdel Wahab Al senosy, Hanan A. Ghoniem, Sahar Fayez, Mohamed F. Zeweil
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Hypoglycemic, Hypolipidemic and Antioxidant Potentials of Ethanolic Stem Bark Extract of Anacardium occidentale in Streptozotocin-Induced Diabetic Rats
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Protective Effects of the Bilobalide on Retinal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats
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Myricitrin and Its Solid Lipid Nanoparticle Increase Insulin Secretion and Content of Isolated Islets from the Pancreas of Male Mice
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Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin
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Protective Effects of Iridoid Glycoside from Corni Fructus on Type 2 Diabetes with Nonalcoholic Fatty Liver in Mice
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Microdose Lithium Protects against Pancreatic Islet Destruction and Renal Impairment in Streptozotocin-Elicited Diabetes
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Antioxidants.2021; 10(1): 138. CrossRef
p-Terphenyls From Aspergillus sp. GZWMJZ-055: Identification, Derivation, Antioxidant and α-Glycosidase Inhibitory Activities
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Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis
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IRS‐2/Akt/GSK‐3β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity
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Effect of propolis on glycemic control in patients with type 2 diabetes: an updated systematic review and meta-analysis of randomized controlled trials
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The Correlation between Selenium Dependent Glutathione Peroxidase Activity and Oxidant/Antioxidant Balance in Sera of Diabetic Patients with Nephropathy
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The Mechanisms and Management of Age-Related Oxidative Stress in Male Hypogonadism Associated with Non-communicable Chronic Disease
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Роль системы врождённого иммунитета и окислительного стресса в развитии сахарного диабета 1-типа. Пероксиредоксин 6 как новый антидиабетический препарат
Е.Г. Новосёлова, О.В. Глушкова, М.О. Хренов, С.М. Лунин, Т.В. Новосёлова, С.Б. Парфенюк
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Participation of Hsp70 and Hsp90α Heat Shock Proteins in Stress Response in the Course of Type 1 Diabetes Mellitus
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The correlation between blood oxidative stress and sialic acid content in diabetic patients with nephropathy, hypertension, and hyperlipidemia
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Green synthesis of gold nanoparticles from Fritillaria cirrhosa and its anti-diabetic activity on Streptozotocin induced rats
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The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases
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Pharmacological and Advanced Cell Respiration Effects, Enhanced by Toxic Human-Bile Nano-Pharmaceuticals of Probucol Cell-Targeting Formulations
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Triglyceride is independently correlated with insulin resistance and islet beta cell function: a study in population with different glucose and lipid metabolism states
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Protective Effects of Grape Seed Proanthocyanidins on the Kidneys of Diabetic Rats through the Nrf2 Signalling Pathway
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The Role of CD36 in Type 2 Diabetes Mellitus: β-Cell Dysfunction and Beyond
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International Journal of Molecular Sciences.2020; 21(9): 3289. CrossRef
Antioxidant and prebiotic effects of a beverage composed by tropical fruits and yacon in alloxan-induced diabetic rats
Ana Paula DIONISIO, Luciano Bruno de CARVALHO-SILVA, Nara Menezes VIEIRA, Nedio Jair WURLITZER, Ana Carolina da Silva PEREIRA, Maria de Fatima BORGES, Deborah dos Santos GARRUTI, Idila dos Santos ARAÚJO
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Rosemary Leaf Extract Inhibits Glycation, Breast Cancer Proliferation, and Diabetes Risks
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Trigonella stellata reduced the deleterious effects of diabetes mellitus through alleviation of oxidative stress, antioxidant- and drug-metabolizing enzymes activities
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A Shift Toward a Plant-Centered Diet From Young to Middle Adulthood and Subsequent Risk of Type 2 Diabetes and Weight Gain: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
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Ascorbic acid supplementation in type 2 diabetes mellitus
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Analysis of the Effect of Fish Bars Made of Bilih Fish (Mystacoleuseus padangensis Blkr) Flour to Reduce Oxidative Stress in a Diabetic Rat Model
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Antioxidant activity of crude ethanolic extract and fractions of Ziziphus mauritiana Lam. (Rhamnaceae) leaves from Burkina Faso
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CD36 dependent redoxosomes promotes ceramide-mediated pancreatic β-cell failure via p66Shc activation
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Comparative proteomic analysis reveals drug resistance of Staphylococcus xylosus ATCC700404 under tylosin stress
Xin Liu, Jinpeng Wang, Mo Chen, Ruixiang Che, Wenya Ding, Fei Yu, Yonghui Zhou, Wenqiang Cui, Xing Xiaoxu, Bello-Onaghise God’spower, Yanhua Li
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The Potential of Bilih Fish (Mystacoleuseus padangensis Blkr) Flour as a Zinc Source to Control Blood Glucose and Impact on Oxidative Stress in a Diabetic Rat Model
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Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments
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The variations of some salivary parameters as probable indices of the hereditary diabetes
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International Journal of Preventive Medicine.2019; 10(1): 11. CrossRef
The Interrelationship between Job Stress with the Immune System and Functional Memory of Women Working in Diagnostic Laboratories
Mansoureh Sadeghi-Yarandi, Anahita Khodabakhshi-Koolaee, Mohammad Reza Falsafinejad, Neda Khaletbari
The Neuroscience Journal of Shefaye Khatam.2019; 7(2): 23. CrossRef
Effect of Cinnamon Administration on Fertility of Normal and Diabetic Male Rats
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Pakistan Journal of Nutrition.2019; 18(5): 491. CrossRef
White Sesame Seed Oil Mitigates Blood Glucose Level, Reduces Oxidative Stress, and Improves Biomarkers of Hepatic and Renal Function in Participants with Type 2 Diabetes Mellitus
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Effect of combination of Gynura procumbens aqueous extract and Trigona spp. honey on fertility and libido of streptozotocin-induced hyperglycaemic male rats
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Asian Pacific Journal of Reproduction.2019; 8(2): 56. CrossRef
Serum Antioxidant Parameters are Significantly Increased in Patients with Type 2 Diabetes Mellitus after Consumption of Chinese Propolis: A Randomized Controlled Trial Based on Fasting Serum Glucose Level
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Diabetes Therapy.2018; 9(1): 101. CrossRef
Baccharis trimera (Carqueja) Improves Metabolic and Redox Status in an Experimental Model of Type 1 Diabetes
Natália Nogueira do Nascimento Kaut, Ana Carolina Silveira Rabelo, Glaucy Rodrigues Araujo, Jason Guy Taylor, Marcelo Eustáquio Silva, Maria Lúcia Pedrosa, Miriam Martins Chaves, Joamyr Victor Rossoni Junior, Daniela Caldeira Costa, Laura De Martino
Evidence-Based Complementary and Alternative Medicine.2018;[Epub] CrossRef
The Potential of South African Herbal Tisanes, Rooibos and Honeybush in the Management of Type 2 Diabetes Mellitus
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Clinical variables and ethnicity may influenced by polymorphism of CAT −262C/T and MnSOD 47C/T antioxidant enzymes in Algerian type1 diabetes without complications
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Crystal structure and functional characterization of selenocysteine-containing glutathione peroxidase 4 suggests an alternative mechanism of peroxide reduction
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The effects of green cardamom supplementation on blood glucose, lipids profile, oxidative stress, sirtuin-1 and irisin in type 2 diabetic patients: a study protocol for a randomized placebo-controlled clinical trial
Mohadeseh Aghasi, Shohreh Ghazi-Zahedi, Fariba Koohdani, Fereydoun Siassi, Ensieh Nasli-Esfahani, Ali Keshavarz, Mostafa Qorbani, Hoorieh Khoshamal, Asma Salari-Moghaddam, Gity Sotoudeh
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Mice pancreatic islets protection from oxidative stress induced by single-walled carbon nanotubes through naringin
A Ahangarpour, S Alboghobeish, AA Oroojan, MA Dehghani
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Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: An update on glucose toxicity
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Cognitive dysfunction and metabolic comorbidities in mood disorders: A repurposing opportunity for glucagon-like peptide 1 receptor agonists?
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Neuropharmacology.2018; 136: 335. CrossRef
The protective effects of a novel synthetic β-elemene derivative on human umbilical vein endothelial cells against oxidative stress-induced injury: Involvement of antioxidation and PI3k/Akt/eNOS/NO signaling pathways
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Curcumin alleviates liver oxidative stress in type 1 diabetic rats
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Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders
Rodrigo B. Mansur, Andre Zugman, Juhie Ahmed, Danielle S. Cha, Mehala Subramaniapillai, Yena Lee, Julie Lovshin, Jung G. Lee, Jae-Hon Lee, Vladislav Drobinin, Jason Newport, Elisa Brietzke, Eva Z. Reininghaus, Kang Sim, Maj Vinberg, Natalie Rasgon, Tomas
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Plasma vascular endothelial growth factor B levels are increased in patients with newly diagnosed type 2 diabetes mellitus and associated with the first phase of glucose-stimulated insulin secretion function of β-cell
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Associations of Dietary Antioxidants and Risk of Type 2 Diabetes: Data from the 2007–2012 Korea National Health and Nutrition Examination Survey
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Curcumin attenuates oxidative stress in liver in Type 1 diabetic rats
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Open Life Sciences.2017; 12(1): 452. CrossRef
Metabolic control and periodontal treatment decreases elevated oxidative stress in the early phases of type 1 diabetes onset
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C-X-C motif chemokine ligand 8 promotes endothelial cell homing via the Akt-signal transducer and activator of transcription pathway to accelerate healing of ischemic and hypoxic skin ulcers
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Current views on neuropeptide Y and diabetes-related atherosclerosis
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Teucrium polium extract reverses symptoms of streptozotocin-induced diabetes in rats via rebalancing the Pdx1 and FoxO1 expressions
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Morin activates the Nrf2-ARE pathway and reduces oxidative stress-induced DNA damage in pancreatic beta cells
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Metformin prevents glucotoxicity by alleviating oxidative and ER stress–induced CD36 expression in pancreatic beta cells
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Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy
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Cicero Diego Almino Menezes, Francisca Adilfa de Oliveira Garcia, Glauce Socorro de Barros Viana, Patricia Gonçalves Pinheiro, Cícero Francisco Bezerra Felipe, Thaís Rodrigues de Albuquerque, Alisson Cordeiro Moreira, Enaide Soares Santos, Maynara Rodrigu
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Fuel-Stimulated Insulin Secretion Depends upon Mitochondria Activation and the Integration of Mitochondrial and Cytosolic Substrate Cycles: Gary W. Cline; Diabetes Metab J. 2011;35(5):458-465. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.458

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The pancreatic islet β-cell is uniquely specialized to couple its metabolism and rates of insulin secretion with the levels of circulating nutrient fuels, with the mitochondrial playing a central regulatory role in this process. In the β-cell, mitochondrial activation generates an integrated signal reflecting rates of oxidativephosphorylation, Kreb's cycle flux, and anaplerosis that ultimately determines the rate of insulin exocytosis. Mitochondrial activation can be regulated by proton leak and mediated by UCP2, and by alkalinization to utilize the pH gradient to drive substrate and ion transport. Converging lines of evidence support the hypothesis that substrate cycles driven by rates of Kreb's cycle flux and by anaplerosis play an integral role in coupling responsive changes in mitochondrial metabolism with insulin secretion. The components and mechanisms that account for the integrated signal of ATP production, substrate cycling, the regulation of cellular redox state, and the production of other secondary signaling intermediates are operative in both rodent and human islet β-cells.

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