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Sulwon Lecture 2024
Basic and Translational Research
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Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System
Il Rae Park, Yong Geun Chung, Kyu Chang Won
Diabetes Metab J. 2025;49(1):1-12.   Published online January 1, 2025
DOI: https://doi.org/10.4093/dmj.2024.0796
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AbstractAbstract PDFPubReader   ePub   
Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation. Targeting CD36 pathways has emerged as a promising therapeutic strategy. Oral hypoglycemic agents, such as metformin, teneligliptin, and pioglitazone, have shown protective effects on β-cells by enhancing antioxidant defenses. These agents reduce glucotoxicity via mechanisms such as suppressing CD36 expression and stabilizing mitochondrial function. Additionally, novel insights into the glutathione antioxidant system and its role in β-cell survival underscore its therapeutic potential. This review focuses on the key contribution of oxidative stress and CD36 to β-cell impairment, the therapeutic promise of antioxidants, and the need for further research to apply these findings in clinical practice. Promising strategies targeting these mechanisms may help preserve β-cell function and slow T2DM progression.
Brief Report
Type 1 Diabetes
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In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors
Seung-Ah Lee, Subin Kim, Seog-Young Kim, Jong Yoen Park, Hye Seung Jung, Sung Soo Chung, Kyong Soo Park
Diabetes Metab J. 2025;49(1):150-159.   Published online October 24, 2024
DOI: https://doi.org/10.4093/dmj.2024.0174
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Four soluble factors—putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102—were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45–55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.
Original Article
Basic Research
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NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9
Xiaolong Li, Yan Cai, Zhu Zhong, Maolin Li, Dong Huang, Zhifei Qiao, Hongli Zhou, Zuo Zhang, Jiyin Zhou
Received September 25, 2023  Accepted February 22, 2024  Published online July 23, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0342    [Epub ahead of print]
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AbstractAbstract PDFPubReader   ePub   
Background
Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear.
Methods
Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA).
Results
In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939.
Conclusion
The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.
Reviews
Metabolic Risk/Epidemiology
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Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome
Scott L. Friedman
Diabetes Metab J. 2024;48(2):161-169.   Published online January 26, 2024
DOI: https://doi.org/10.4093/dmj.2023.0240
  • 5,945 View
  • 443 Download
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
Metabolic dysfunction-associated steatotic (fatty) liver disease (MASLD), previously termed non-alcoholic fatty liver disease, is a worldwide epidemic that can lead to hepatic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The disease is typically a component of the metabolic syndrome that accompanies obesity, and is often overlooked because the liver manifestations are clinically silent until late-stage disease is present (i.e., cirrhosis). Moreover, Asian populations, including Koreans, have a higher fraction of patients who are lean, yet their illness has the same prognosis or worse than those who are obese. Nonetheless, ongoing injury can lead to hepatic inflammation and ballooning of hepatocytes as classic features. Over time, fibrosis develops following activation of hepatic stellate cells, the liver’s main fibrogenic cell type. The disease is usually more advanced in patients with type 2 diabetes mellitus, indicating that all diabetic patients should be screened for liver disease. Although there has been substantial progress in clarifying pathways of injury and fibrosis, there no approved therapies yet, but current research seeks to uncover the pathways driving hepatic inflammation and fibrosis, in hopes of identifying new therapeutic targets. Emerging molecular methods, especially single cell sequencing technologies, are revolutionizing our ability to clarify mechanisms underlying MASLD-associated fibrosis and HCC.

Citations

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    Heliyon.2024; 10(19): e38339.     CrossRef
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    Daniela Gabbia
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    Michal Selc, Radka Macova, Andrea Babelova
    Drug Design, Development and Therapy.2024; Volume 18: 4629.     CrossRef
  • Valorizing Agro‐Food Waste for Nutraceutical Development: Sustainable Approaches for Managing Metabolic Dysfunction‐Associated Steatotic Liver Disease and Related Co‐Morbidities
    Laura Comi, Claudia Giglione, Fationa Tolaj Klinaku, Federico Pialorsi, Valentina Tollemeto, Maria Zurlo, Antonio Seneci, Paolo Magni
    Food Frontiers.2024;[Epub]     CrossRef
Basic Research
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Rediscovering Primary Cilia in Pancreatic Islets
Eun Young Lee, Jing W. Hughes
Diabetes Metab J. 2023;47(4):454-469.   Published online April 28, 2023
DOI: https://doi.org/10.4093/dmj.2022.0442
  • 4,637 View
  • 289 Download
  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFPubReader   ePub   
Primary cilia are microtubule-based sensory and signaling organelles on the surfaces of most eukaryotic cells. Despite their early description by microscopy studies, islet cilia had not been examined in the functional context until recent decades. In pancreatic islets as in other tissues, primary cilia facilitate crucial developmental and signaling pathways in response to extracellular stimuli. Many human developmental and genetic disorders are associated with ciliary dysfunction, some manifesting as obesity and diabetes. Understanding the basis for metabolic diseases in human ciliopathies has been aided by close examination of cilia action in pancreatic islets at cellular and molecular levels. In this article, we review the evidence for ciliary expression on islet cells, known roles of cilia in pancreas development and islet hormone secretion, and summarize metabolic manifestations of human ciliopathy syndromes. We discuss emerging data on primary cilia regulation of islet cell signaling and the structural basis of cilia-mediated cell crosstalk, and offer our interpretation on the role of cilia in glucose homeostasis and human diseases.

Citations

Citations to this article as recorded by  
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    Bang‐Hua Zhong, Ning Nie, Ming Dong
    Obesity Reviews.2025;[Epub]     CrossRef
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    Life Science Alliance.2025; 8(2): e202402916.     CrossRef
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    Asma A Elashi, Salman M Toor, Umm-Kulthum Ismail Umlai, Yasser A Al-Sarraj, Shahrad Taheri, Karsten Suhre, Abdul Badi Abou-Samra, Omar M E Albagha
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Basic Research
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Regulation of Cellular Senescence in Type 2 Diabetes Mellitus: From Mechanisms to Clinical Applications
Kanako Iwasaki, Cristian Abarca, Cristina Aguayo-Mazzucato
Diabetes Metab J. 2023;47(4):441-453.   Published online March 6, 2023
DOI: https://doi.org/10.4093/dmj.2022.0416
  • 8,536 View
  • 576 Download
  • 14 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   ePub   
Cellular senescence is accelerated by hyperglycemia through multiple pathways. Therefore, senescence is an important cellular mechanism to consider in the pathophysiology of type 2 diabetes mellitus (T2DM) and an additional therapeutic target. The use of drugs that remove senescent cells has led to improvements in blood glucose levels and diabetic complications in animal studies. Although the removal of senescent cells is a promising approach for the treatment of T2DM, two main challenges limit its clinical application: the molecular basis of cellular senescence in each organ is yet to be understood, and the specific effect of removing senescent cells in each organ has to be determined. This review aims to discuss future applications of targeting senescence as a therapeutic option in T2DM and elucidate the characteristics of cellular senescence and senescence-associated secretory phenotype in the tissues important for regulating glucose levels: pancreas, liver, adipocytes, and skeletal muscle.

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Original Article
Basic Research
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Hyperglycemia-Suppressed SMARCA5 Disrupts Transcriptional Homeostasis to Facilitate Endothelial Dysfunction in Diabetes
Ju Wang, Hui Zhou, Jinhua Shao, Shu Zhang, Jing Jin
Diabetes Metab J. 2023;47(3):366-381.   Published online March 6, 2023
DOI: https://doi.org/10.4093/dmj.2022.0179
  • 3,026 View
  • 119 Download
  • 4 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Dysfunction of vascular endothelial cells (ECs) plays a central role in the pathogenesis of cardiovascular complications in diabetes. SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) is a key regulator of chromatin structure and DNA repair, but its role in ECs remains surprisingly unexplored. The current study was designed to elucidate the regulated expression and function of SMARCA5 in diabetic ECs.
Methods
SMARCA5 expression was evaluated in ECs from diabetic mouse and human circulating CD34+ cells using quantitative reverse transcription polymerase chain reaction and Western blot. Effects of SMARCA5 manipulation on ECs function were evaluated using cell migration, in vitro tube formation and in vivo wound healing assays. Interaction among oxidative stress, SMARCA5 and transcriptional reprogramming was elucidated using luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation.
Results
Endothelial SMARCA5 expression was significantly decreased in diabetic rodents and humans. Hyperglycemia-suppressed SMARCA5 impaired EC migration and tube formation in vitro, and blunted vasculogenesis in vivo. Contrarily, overexpression of SMARCA5 in situ by a SMARCA5 adenovirus-incorporated hydrogel effectively promoted the rate of wound healing in a dorsal skin punch injury model of diabetic mice. Mechanistically, hyperglycemia-elicited oxidative stress suppressed SMARCA5 transactivation in a signal transducer and activator of transcription 3 (STAT3)-dependent manner. Moreover, SMARCA5 maintained transcriptional homeostasis of several pro-angiogenic factors through both direct and indirect chromatin-remodeling mechanisms. In contrast, depletion of SMARCA5 disrupted transcriptional homeostasis to render ECs unresponsive to established angiogenic factors, which ultimately resulted in endothelial dysfunction in diabetes.
Conclusion
Suppression of endothelial SMARCA5 contributes to, at least in part, multiple aspects of endothelial dysfunction, which may thereby exacerbate cardiovascular complications in diabetes.

Citations

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Reviews
Basic Research
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Heterogeneity of Islet Cells during Embryogenesis and Differentiation
Shugo Sasaki, Takeshi Miyatsuka
Diabetes Metab J. 2023;47(2):173-184.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0324
  • 5,436 View
  • 283 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Diabetes is caused by insufficient insulin secretion due to β-cell dysfunction and/or β-cell loss. Therefore, the restoration of functional β-cells by the induction of β-cell differentiation from embryonic stem (ES) and induced-pluripotent stem (iPS) cells, or from somatic non-β-cells, may be a promising curative therapy. To establish an efficient and feasible method for generating functional insulin-producing cells, comprehensive knowledge of pancreas development and β-cell differentiation, including the mechanisms driving cell fate decisions and endocrine cell maturation is crucial. Recent advances in single-cell RNA sequencing (scRNA-seq) technologies have opened a new era in pancreas development and diabetes research, leading to clarification of the detailed transcriptomes of individual insulin-producing cells. Such extensive high-resolution data enables the inference of developmental trajectories during cell transitions and gene regulatory networks. Additionally, advancements in stem cell research have not only enabled their immediate clinical application, but also has made it possible to observe the genetic dynamics of human cell development and maturation in a dish. In this review, we provide an overview of the heterogeneity of islet cells during embryogenesis and differentiation as demonstrated by scRNA-seq studies on the developing and adult pancreata, with implications for the future application of regenerative medicine for diabetes.

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    Dan Kawamori, Shugo Sasaki
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Pathophysiology
Article image
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
  • 6,282 View
  • 277 Download
  • 16 Web of Science
  • 16 Crossref
AbstractAbstract PDFPubReader   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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    Hayder M. Al-kuraishy, Majid S. Jabir, Ali I. Al-Gareeb, Daniel J. Klionsky, Ali K. Albuhadily
    Autophagy.2024; 20(11): 2361.     CrossRef
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Pathophysiology
Glial and Vascular Cell Regulation of the Blood-Brain Barrier in Diabetes
Xiaolong Li, Yan Cai, Zuo Zhang, Jiyin Zhou
Diabetes Metab J. 2022;46(2):222-238.   Published online March 18, 2022
DOI: https://doi.org/10.4093/dmj.2021.0146
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AbstractAbstract PDFPubReader   ePub   
As a structural barrier, the blood-brain barrier (BBB) is located at the interface between the brain parenchyma and blood, and modulates communication between the brain and blood microenvironment to maintain homeostasis. The BBB is composed of endothelial cells, basement membrane, pericytes, and astrocytic end feet. BBB impairment is a distinguishing and pathogenic factor in diabetic encephalopathy. Diabetes causes leakage of the BBB through downregulation of tight junction proteins, resulting in impaired functioning of endothelial cells, pericytes, astrocytes, microglia, nerve/glial antigen 2-glia, and oligodendrocytes. However, the temporal regulation, mechanisms of molecular and signaling pathways, and consequences of BBB impairment in diabetes are not well understood. Consequently, the efficacy of therapies diabetes targeting BBB leakage still lags behind the requirements. This review summarizes the recent research on the effects of diabetes on BBB composition and the potential roles of glial and vascular cells as therapeutic targets for BBB disruption in diabetic encephalopathy.

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Islet Studies and Transplantation
Article image
Regulation of Pancreatic β-Cell Mass by Gene-Environment Interaction
Shun-ichiro Asahara, Hiroyuki Inoue, Yoshiaki Kido
Diabetes Metab J. 2022;46(1):38-48.   Published online January 27, 2022
DOI: https://doi.org/10.4093/dmj.2021.0045
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The main pathogenic mechanism of diabetes consists of an increase in insulin resistance and a decrease in insulin secretion from pancreatic β-cells. The number of diabetic patients has been increasing dramatically worldwide, especially in Asian people whose capacity for insulin secretion is inherently lower than that of other ethnic populations. Causally, changes of environmental factors in addition to intrinsic genetic factors have been considered to have an influence on the increased prevalence of diabetes. Particular focus has been placed on “gene-environment interactions” in the development of a reduced pancreatic β-cell mass, as well as type 1 and type 2 diabetes mellitus. Changes in the intrauterine environment, such as intrauterine growth restriction, contribute to alterations of gene expression in pancreatic β-cells, ultimately resulting in the development of pancreatic β-cell failure and diabetes. As a molecular mechanism underlying the effect of the intrauterine environment, epigenetic modifications have been widely investigated. The association of diabetes susceptibility genes or dietary habits with gene-environment interactions has been reported. In this review, we provide an overview of the role of gene-environment interactions in pancreatic β-cell failure as revealed by previous reports and data from experiments.

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Short Communication
Basic Research
Article image
GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells
Joo Won Kim, Eun Roh, Kyung Mook Choi, Hye Jin Yoo, Hwan-Jin Hwang, Sei Hyun Baik
Diabetes Metab J. 2022;46(3):506-511.   Published online January 24, 2022
DOI: https://doi.org/10.4093/dmj.2021.0092
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AbstractAbstract PDFPubReader   ePub   
Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB activation. LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium.

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Original Articles
Pathophysiology
Article image
Relationships between Islet-Specific Autoantibody Titers and the Clinical Characteristics of Patients with Diabetes Mellitus
Yiqian Zhang, Tong Yin, Xinlei Wang, Rongping Zhang, Jie Yuan, Yi Sun, Jing Zong, Shiwei Cui, Yunjuan Gu
Diabetes Metab J. 2021;45(3):404-416.   Published online July 21, 2020
DOI: https://doi.org/10.4093/dmj.2019.0239
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.

Methods

A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.

Results

Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.

Conclusion

Diabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

Citations

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Basic Research
Article image
Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell
Kyung-Soo Kim, Yeon Kyung Choi, Mi Jin Kim, Jung Wook Hwang, Kyunghoon Min, Sang Youn Jung, Soo-Kyung Kim, Yong-Soo Choi, Yong-Wook Cho
Diabetes Metab J. 2021;45(2):260-269.   Published online July 10, 2020
DOI: https://doi.org/10.4093/dmj.2019.0191
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.

Methods

Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.

Results

Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.

Conclusion

UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

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Basic Research
Article image
Hypoxia Increases β-Cell Death by Activating Pancreatic Stellate Cells within the Islet
Jong Jin Kim, Esder Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Ki-Ho Song
Diabetes Metab J. 2020;44(6):919-927.   Published online May 11, 2020
DOI: https://doi.org/10.4093/dmj.2019.0181
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AbstractAbstract PDFPubReader   ePub   
Background

Hypoxia can occur in pancreatic islets in type 2 diabetes mellitus. Pancreatic stellate cells (PSCs) are activated during hypoxia. Here we aimed to investigate whether PSCs within the islet are also activated in hypoxia, causing β-cell injury.

Methods

Islet and primary PSCs were isolated from Sprague Dawley rats, and cultured in normoxia (21% O2) or hypoxia (1% O2). The expression of α-smooth muscle actin (α-SMA), as measured by immunostaining and Western blotting, was used as a marker of PSC activation. Conditioned media (hypoxia-CM) were obtained from PSCs cultured in hypoxia.

Results

Islets and PSCs cultured in hypoxia exhibited higher expressions of α-SMA than did those cultured in normoxia. Hypoxia increased the production of reactive oxygen species. The addition of N-acetyl-L-cysteine, an antioxidant, attenuated the hypoxia-induced PSC activation in islets and PSCs. Islets cultured in hypoxia-CM showed a decrease in cell viability and an increase in apoptosis.

Conclusion

PSCs within the islet are activated in hypoxia through oxidative stress and promote islet cell death, suggesting that hypoxia-induced PSC activation may contribute to β-cell loss in type 2 diabetes mellitus.

Citations

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