Diabetes & Metabolism Journal

Original Articles

Obesity and Metabolic Syndrome
Importance of Lean Muscle Maintenance to Improve Insulin Resistance by Body Weight Reduction in Female Patients with Obesity: Yaeko Fukushima, Satoshi Kurose, Hiromi Shinno, Ha Cao Thu, Nana Takao, Hiromi Tsutsumi, Yutaka Kimura; Diabetes Metab J. 2016;40(2):147-153. Published online March 27, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.2.147

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Background

It has recently been suggested that skeletal muscle has an important role in insulin resistance in obesity, in addition to exercise tolerance and the fat index. The aim of this study was to identify body composition factors that contribute to improvement of insulin resistance in female patients with obesity who reduce body weight.

Methods

We studied 92 female obese patients (age 40.9±10.4 years, body mass index 33.2±4.6 kg/m²) who reduced body weight by ≥5% after an intervention program including diet, exercise therapy, and cognitive behavioral therapy. Before and after the intervention, body composition was evaluated by dual-energy X-ray absorptiometry to examine changes in skeletal muscle mass. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured as an index of insulin resistance. Cardiopulmonary exercise was also performed by all patients.

Results

There were significant improvements in body weight (–10.3%±4.5%), exercise tolerance (anaerobic threshold oxygen uptake 9.1%±18.4%, peak oxygen uptake 11.0%±14.2%), and HOMA-IR (–20.2%±38.3%). Regarding body composition, there were significant decreases in total body fat (–19.3%±9.6%), total fat-free mass (–2.7%±4.3%), and % body fat (–10.1%±7.5%), whereas % skeletal muscle significantly increased (8.9%±7.2%). In stepwise multiple linear regression analysis with change in HOMA-IR as the dependent variable, the change in % skeletal muscle was identified as an independent predictor (β=–0.280, R²=0.068, P<0.01).

Conclusion

Improvement of insulin resistance in female obese patients requires maintenance of skeletal muscle mass.

Citations

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Journal of Surgery and Medicine.2024; 8(4): 73. CrossRef
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Yue-Heng Yin, Justina Yat Wa Liu, Maritta Välimäki
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Journal of Physical Activity and Health.2022; 19(5): 351. CrossRef
Interrelationship of Gut Microbiota, Obesity, Body Composition and Insulin Resistance in Asians with Type 2 Diabetes Mellitus
Che-Sheng Pai, Cheng-Yuan Wang, Wei-Wen Hung, Wei-Chun Hung, Hui-Ju Tsai, Chen-Chia Chang, Shang-Jyh Hwang, Chia-Yen Dai, Wen-Yu Ho, Yi-Chun Tsai
Journal of Personalized Medicine.2022; 12(4): 617. CrossRef
Exercise and Nutrition Strategies for Combating Sarcopenia and Type 2 Diabetes Mellitus in Older Adults
Dionysia Argyropoulou, Nikolaos D. Geladas, Tzortzis Nomikos, Vassilis Paschalis
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Magnoudewa Priscille Pana, Pierre Ayotte, Elhadji Anassour-Laouan-Sidi, Edouard Suhas, Clémence Mahana Iti Gatti, Michel Lucas
Metabolites.2022; 12(7): 589. CrossRef
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Jasmine Paquin, Jean-Christophe Lagacé, Martin Brochu, Isabelle J. Dionne
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Nana Takao, Satoshi Kurose, Takumi Miyauchi, Katsuko Onishi, Atsuko Tamanoi, Ryota Tsuyuguchi, Aya Fujii, Sawako Yoshiuchi, Kazuhisa Takahashi, Hiromi Tsutsumi, Yutaka Kimura
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Babu R. Maharjan, Sergio F. Martinez‐Huenchullan, Susan V. Mclennan, Stephen M. Twigg, Paul F. Williams
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International Journal of Research -GRANTHAALAYAH.2020; 8(3): 271. CrossRef
Epicardial adipose tissue is tightly associated with exercise intolerance in patients with type 2 diabetes mellitus with asymptomatic left ventricular structural and functional abnormalities
Yousuke Sugita, Katsuhiko Ito, Shigeki Sakurai, Satoshi Sakai, Shinya Kuno
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Anna Thorsø Larsen, Nina Sonne, Kim V. Andreassen, Morten A. Karsdal, Kim Henriksen
Journal of Pharmacology and Experimental Therapeutics.2020; 373(2): 269. CrossRef
Healthy dietary pattern and their corresponding gut microbiota profile are linked to a lower risk of type 2 diabetes, independent of the presence of obesity
D.A. Díaz-Rizzolo, B. Kostov, M. López-Siles, A. Serra, C. Colungo, L. González-de-Paz, M. Martinez-Medina, A. Sisó-Almirall, R. Gomis
Clinical Nutrition.2020; 39(2): 524. CrossRef
Changes in Body Composition and FTO Whole Blood DNA Methylation Among Japanese Women: A Randomized Clinical Trial of Weight-Loss Program

Haruhiko Nishida, Katsuko Onishi, Satoshi Kurose, Hiromi Tsutsumi, Takumi Miyauchi, Nana Takao, Sawako Yoshiuchi, Aya Fujii, Yutaka Kimura
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 2157. CrossRef
Effects of low skeletal muscle mass and sarcopenic obesity on albuminuria: a 7-year longitudinal study
Jee Hee Yoo, Gyuri Kim, Sung Woon Park, Min Sun Choi, Jiyeon Ahn, Sang-Man Jin, Kyu Yeon Hur, Moon-Kyu Lee, Mira Kang, Jae Hyeon Kim
Scientific Reports.2020;[Epub] CrossRef
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Gian Pietro Emerenziani, Dafne Ferrari, Silvia Migliaccio, Andrea Lenzi, Emanuela A. Greco, Chiara Marocco, Carlo Baldari, Laura Guidetti
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Shirine Khazem, Leila Itani, Dima Kreidieh, Dana El Masri, Hana Tannir, Roberto Citarella, Marwan El Ghoch
International Journal of Environmental Research and Public Health.2018; 15(12): 2754. CrossRef
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M. El Ghoch, A.P. Rossi, S. Calugi, S. Rubele, F. Soave, M. Zamboni, E. Chignola, G. Mazzali, P.V. Bazzani, R. Dalle Grave
Nutrition, Metabolism and Cardiovascular Diseases.2018; 28(9): 917. CrossRef
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V. E. Bianchi, V. Locatelli
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Burly1 is a mouse QTL for lean body mass that maps to a 0.8-Mb region of chromosome 2
Cailu Lin, Brad D. Fesi, Michael Marquis, Natalia P. Bosak, Anna Lysenko, Mohammed Amin Koshnevisan, Fujiko F. Duke, Maria L. Theodorides, Theodore M. Nelson, Amanda H. McDaniel, Mauricio Avigdor, Charles J. Arayata, Lauren Shaw, Alexander A. Bachmanov, D
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Hypoxic Training Improves Normoxic Glucose Tolerance in Adolescents with Obesity
ESTELLE DE GROOTE, FLORIAN A. BRITTO, LOÏC BULLOCK, MARIE FRANÇOIS, CARINE DE BUCK, HENRI NIELENS, LOUISE DELDICQUE
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Lipid modulation of skeletal muscle mass and function
Christopher Lipina, Harinder S Hundal
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Angiotensin-Converting Enzyme Ins/Del Polymorphism and Body Composition: The Intermediary Role of Hydration Status
Laura Bordoni, Valerio Napolioni, Francesca Marchegiani, Emilio Amadio, Rosita Gabbianelli
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K. R. Hirsch, A. E. Smith-Ryan, M. N. M. Blue, M. G. Mock, E. T. Trexler
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Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?
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Mediterranean diet and mortality risk in metabolically healthy obese and metabolically unhealthy obese phenotypes
Y-M Park, S E Steck, T T Fung, J Zhang, L J Hazlett, K Han, A T Merchant
International Journal of Obesity.2016; 40(10): 1541. CrossRef
Effects of Body Weight Reduction on Serum Irisin and Metabolic Parameters in Obese Subjects
Yaeko Fukushima, Satoshi Kurose, Hiromi Shinno, Ha Cao Thi Thu, Nana Takao, Hiromi Tsutsumi, Takaaki Hasegawa, Toshiaki Nakajima, Yutaka Kimura
Diabetes & Metabolism Journal.2016; 40(5): 386. CrossRef

Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus: Shusuke Yagi, Ken-ichi Aihara, Masashi Akaike, Daiju Fukuda, Hotimah Masdan Salim, Masayoshi Ishida, Tomomi Matsuura, Takayuki Ise, Koji Yamaguchi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Toshio Matsumoto, Masataka Sata; Diabetes Metab J. 2015;39(4):342-347. Published online July 21, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.4.342

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Abstract PDF PubReader

Background

Predictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors for lowering glycosylated hemoglobin (HbA1c) remain unclear in patients with type 2 diabetes mellitus. The aim of this study is therefore to clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c after 12 months of treatment.

Methods

A total of 191 consecutive type 2 diabetic patients (male sex 55%, mean age, 68.3±35.8 years), who had been treated with DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated retrospectively.

Results

After 12 months of DPP-4 inhibitor treatment, random blood glucose level, and HbA1c level, decreased from 167±63 to 151±49 mg/dL (P<0.01), and from 7.5%±1.3% to 6.9%±0.9% (P<0.01) respectively, without severe side effects. Multiple regression analysis showed that predictors of DPP-4 inhibitor treatment efficacy in lowering HbA1c level after 12 months were a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and the absence of coronary artery disease.

Conclusion

Most suitable candidates for treatment with DPP-4 inhibitors are diabetics who are not obese and do not have coronary artery disease. In addition, long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c after 3 months of treatment.

Citations

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Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes
Shiau Chin Chong, Norlela Sukor, Sarah Anne Robert, Kim Fong Ng, Nor Azmi Kamaruddin
Frontiers in Endocrinology.2022;[Epub] CrossRef
Dipeptidyl peptidase‐4 inhibitor, anagliptin, alters hepatic insulin clearance in relation to the glycemic status in Japanese individuals with type 2 diabetes
Takahiro Abe, Yasuhiro Matsubayashi, Sayaka Muragishi, Akihiro Yoshida, Hideki Suganami, Kenichi Furusawa, Kazuya Fujihara, Shiro Tanaka, Kohei Kaku, Hirohito Sone
Journal of Diabetes Investigation.2021; 12(10): 1805. CrossRef
Effects of omarigliptin on glucose variability and oxidative stress in type 2 diabetes patients: A prospective study
Makoto Ohara, Hiroe Nagaike, Tomoki Fujikawa, Yo Kohata, Maiho Ogawa, Takemasa Omachi, Risa Sasajima, Hirotoshi Chiba, Toshimasa Ara, Ayuka Sugawara, Munenori Hiromura, Michishige Terasaki, Yusaku Mori, Tomoyasu Fukui, Tsutomu Hirano, Hiroki Yokoyama, Sho
Diabetes Research and Clinical Practice.2021; 179: 108999. CrossRef
Factors associated with the glucose‐lowering efficacy of sitagliptin in Japanese patients with type 2 diabetes mellitus: Pooled analysis of Japanese clinical trials
Naoko Tajima, Jun‐ichi Eiki, Taro Okamoto, Kotoba Okuyama, Masaru Kawashima, Samuel S Engel
Journal of Diabetes Investigation.2020; 11(3): 640. CrossRef
Efficacy and safety of evogliptin versus sitagliptin as add on to metformin alone in a combined russian-korean population. Evo-combi trial
Alina Y. Babenko, Anna A. Mosikian, Igor E. Makarenko, Victoriya V. Leusheva, Evgeny V. Shlyakhto
Diabetes mellitus.2018; 21(4): 241. CrossRef
Predictors for the Treatment Effect of Sodium Glucose Co-transporter 2 Inhibitors in Patients with Type 2 Diabetes Mellitus
Shusuke Yagi, Ken-ichi Aihara, Takeshi Kondo, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Daiju Fukuda, Yutaka Nakaya, Kin-ichiro Suwaki, Takashi Takeji, Toshihiro Wada, Hotimah Masdan Salim, Saori Hama, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Ko
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Yuli Cai, Tianshu Zeng, Zhongyuan Wen, Lulu Chen
Diabetes Therapy.2018; 9(1): 177. CrossRef
Effectiveness prediction of Evogliptin treatment in type 2 diabetes mellitus in russian-korean population
Anna A. Mosikian, Alina Y. Babenko, Yulia A. Sevastyanova, Roman V. Drai, Evgenij V. Shlyakhto
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Guang Ning, Tushar Bandgar, Uwe Hehnke, Jisoo Lee, Juliana C. N. Chan
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Potential regulatory mechanisms of lncRNA in diabetes and its complications
Shui-Dong Feng, Ji-Hua Yang, Chao Hua Yao, Si-Si Yang, Ze-Mei Zhu, Di Wu, Hong-Yan Ling, Liang Zhang
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Xiaoling Cai, Wenjia Yang, Xueying Gao, Lingli Zhou, Xueyao Han, Linong Ji, Francesco Giorgino
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Xiaoling Cai, Wenjia Yang, Yifei Chen, Xueying Gao, Lingli Zhou, Simin Zhang, Xueyao Han, Linong Ji
Expert Opinion on Pharmacotherapy.2016; 17(12): 1591. CrossRef
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Letter: Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2015;39:342-7)
Ye An Kim
Diabetes & Metabolism Journal.2015; 39(5): 444. CrossRef
Response: Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2015;39:342-7)
Shusuke Yagi, Ken-ichi Aihara, Masataka Sata
Diabetes & Metabolism Journal.2015; 39(5): 446. CrossRef

Proinflammatory Cytokines and Insulin Resistance in Nonobsese Women with High Body Fat and Low Fat Free Mass.: Young Sung Suh, In Kyu Lee, Dae Hyun Kim; Korean Diabetes J. 2007;31(2):136-143. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.136

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Abstract PDF

BACKGROUND
Adipose tissue produces and releases a variety of proinflammatory cytokines. The aim of this study was to investigate whether proinflammatory cytokines are increased and insulin resistance is presented in nonobese women with high body fat and low fat free mass. METHODS: Sixty nonobese adult premenopausal women (body mass index, BMI < 25 kg/m2) were included in this study. Body composition was determined by dual energy absoprtiometry (DXA). Fasting glucose, lipid profiles, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C reactive protein (CRP) and basal insulin were measured. RESULTS: The subjects with high body fat (> or = 30%) had higher CRP levels (P = 0.024), IL-6 levels (P = 0.008), insulin levels (P = 0.003), and homeostasis model assessment-IR (HOMA-IR) (P = 0.020) than those of the subjects with low body fat. In a subset of 32 subjects with high body fat (> or = 30%), the number of subjects with high fat free mass index (FFMI) (> or = 13.5 kg/m2) had higher atherogenic index than that of subjects with low FFMI (FFMI < 13.5 kg/m2) (P < 0.05). IL-6 was correlated with % body fat, fat mass index (FMI), and fat mass (P < 0.05). HOMA-IR was correlated with % body fat and FMI (P < 0.05). To investigate predictors of cytokines and HOMA-IR, multiple regression analysis was used. % body fat was a predictor for IL-6 and, while age and % body fat were predictors of HOMA-IR in study subjects. Conclusions: This study suggests that insulin resistance may be present in nonobese women with high body fat and low fat free mass.

Citations

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The Effect of Low Intensity Exercise on Expression of Inflammatory Response and Apoptosis in Rats with Obesity Induced by a High-Fat Diet
Dong-Hun Choi, Joon-Yong Cho
Exercise Science.2018; 27(1): 40. CrossRef
Experiences of Health Related Lifestyles in High Body Fat but Non-obese Female College Students in Korea
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Osong Public Health and Research Perspectives.2014; 5(1): 68. CrossRef

Clinical Characteristics of Non-obese, Adult-onset Diabetes Requiring Insulin Treatment.: Se Eun Park, Wan Sub Shim, Mi Young Do, Eun Seok Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):557-565. Published online November 1, 2005

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Abstract PDF: BACKGROUND
The aim of this study is to clarify the clinical characteristics of non-obese, adult-onset diabetes requiring insulin treatment and to compare the different characteristics of the three groups categorized according to diabetes classification. METHODS: Total 128 diabetic patients who were non-obese (BMI < 25kg/m2) and had been diagnosed with diabetes after 20 years old, requiring insulin treatment were enrolled in the study. We divided the patients into three groups : 56 patients with type 1, 37 with unclassifiable, and 35 with type 2 diabetes. The type of diabetes was assigned by comparing serum C-peptide concentration and clinical phenotypes. RESULTS: Type 2 and unclassifiable diabetes had no differences in BMI, the interval to use insulin, daily insulin dose, the level of HDL cholesterol and the positive rate for GAD Ab, but type 1 diabetes didn't. However, type 1 diabetes and unclassifiable group was lower prevalence of microvascular complications than type 2 diabetes (retinopathy 38.2, 52.8, 84.8 % ; nephropathy 37.7, 36.7, 74.2 % ; neuropathy 36.7, 36.7, 72.7 %, P<0.05). The prevalence of macrovascular complications was higher in the order of type 1, unclassifiable, and type 2 diabetes (11.1, 29.4, 72.7 %, respectively, all P<0.05). CONCLUSION: The clinical characteristics were similar between unclassifiable and type 2 diabetes, but the prevalence of microvascular complication in unclassifiable group had no significant difference compared with type 1 diabetes. The prevalence of macrovascular complications was significantly higher in the order of type 1, unclassifiable, and type 2 diabetes.

Quantification of the Pancreatic -cell Mass in Normal and Type 2 Diabetic Subjects in Korea.: Kun Ho Yoon, Seung Hyun Ko, Jung Min Lee, Sung Rae Kim, Sun Hee Seo, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Yong Gui Kim, In Sung Moon, Myung Deuk Lee, Dong Ku Kim, Kyo Young Lee, Chan Suk Kang, Byung Ki Kim; Korean Diabetes J. 2000;24(5):524-532. Published online January 1, 2001

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Abstract: BACKGROUND
There have been several reports about insulin secretory impairment in non-obese type 2 diabetic patients and even in impaired glucose tolerant subjects in Korea. Insulin secretory impairment might be induced by insufficient beta-cell mass, functional defects of beta-cells or both. To clarify the cause of impaired insulin secretion in type 2 non-obese diabetic patients in Korea, beta- cell masses were quantified in normal and type 2 diabetic subjects. METHOD: Normal pancreases were procured by 6 heart-beating non-diabetic donors under informed consent from relatives and approval of the university ethical committee. To quantify the beta cell mass and insulin content in various part of the pancreas, first we divided it into 3 parts: head, body and tail, and then each three parts were weighed and subdivided again into 8 segments equally. For diabetic patients, tissue sections were obtained from 15 partial or total pancreatectomized type 2 diabetic patients of any causes. After being fixed, tissues were immunostained using the Streptavidin-biotin-peroxidase method with anti-insulin antibody. Beta cells were counted by point count method. RESULTS: The mean value of total pancreas weight of normal subjects (n=6) was 77.1+/-14.6 g, that of mean relative volume of beta cells in the pancreas was 2.1+/- 0.9%, ranging from 1.4% to 3.1% (head 2.3+/-0.6%, body 1.8+/-0.2%, tail 2.2+/-0.4%). Mean value of total beta cell mass which was calculated from relative volume of beta-cells and weight of each portions was 1.3+/-0.3 g, ranging from 1.2 g to 1.9 g (head 0.6+/-0.3 g, body 0.4+/-0.2 g, tail 0.4+/-0.2 g). Mean insulin content per pancreas was 63.6+/-46.6 g, ranging from 27.8 to 137.2 g/pancreas (head 25.1+/- 19.1 g, body 20.8+/-15.5 g, tail 17.7+/-14.9 g). In diabetic patients, relative volume of beta cells in tissues were variable from 0.4% to 2.8% and there was good correlation between beta-cell mass and body mass index of the diabetic patients. However we can't find the correlation among relative volume of beta-cell, (r2=0.55, p<0.05) duration of diabetes and age. Remarkable heterogeneity for loss of beta-cells in the islets of diabetic patients was observed even in the same lobe of pancreas. There were no evidence of lymphocytic infiltration in the islets. CONCLUSION: Insufficient beta cell mass seems to be a main cause for insulin secretory impairment in non-obese type 2 diabetic patients in Korea.

Distinct Pattern of GAD65 and GAD67 Gene Expression in the Pancreas of NOD Mouse.: In Young Ko, Yup Kang; Korean Diabetes J. 1997;21(3):243-253. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Glutamic acid decarboxylase(GAD; EC 4.1.1.15), one of the major B-cell autoantigens in IDDM, is an enzyme which catalyzes the synthesis of major inhibitory neurotransmitter, r-aminobutyric acid (GARA), in the mammalian brain, pancreas and other organs. Two isoforms of GAD, GAD65 and GAD67, have been identified which differ in their intracellular localization. Autoantibodies to GAD have been detected several years before the clinical onset of IDDM, implicating GAD as a leading autoantigen which somehow correlated with the pathogenesis of IDDM. We have determined the characteristics of GAD isoform expression in the pancreas of NOD mouse, an animal model extensively employed in IDDM study, using RT-PCR and Southern blot methods. METHODS: Pancreas was obtained from female NOD mouse(neonate, 4, 8, 12, 16, 20 week-old) and age-matched female ICR mouse. Total cellular RNA was I.solated by acid guanidinium thiocyanate method and employed in the RT-PCR amplification using GAD65- and GAD67-specific primer designed in our laboratory. The PCR product was blotted onto the nylon membrane and subjected to Southern analysis using 32P-ATP labelled hybridization probe. RESULTS: In NOD pancreas, GAD67 was expressed six times higher than GAD65 at neonatal stage. Then, the expression was dramatically decreased from 4 weeks when the pancreatic insulitis begins to occur. After 12 weeks of age, both GAD67 and GAD65 expression was almost undetectable. However, in control ICR mouse, there were no significant differenees between GAD65 and GAD67 expression throughout the ages. And, the expression of both GAD65 and OAD67 was not decreased with ages in contrast to NOD mouse. CONCLUSION: In this experiment, we found that the expression of GAD isoforms in NOD mouse shows distinct pattern in comparison to that of control ICR mouse. The expression of GAD67 was significantly higher than GAD65 in neonatal NOD mouse while, in control ICR mouse, same level of GAD isoforrns expression was observed. This finding clearly suggested the possibility that the expression of GAD isoforms in diabetic NOD mouse is quite distinct and may somehow play a role in the pathogenesis of diabetes although the precise mechanism remains to be unveiled. In addition, our data also supported the hypothesis that expressional pattern, and, if possible, ' the etiophysiological function of GAD isoforms in NOD mouse pancreas may be quite different from that in human pancreas.

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