Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
Comparison of Efficacy of Glimepiride, Alogliptin, and Alogliptin-Pioglitazone as the Initial Periods of Therapy in Patients with Poorly Controlled Type 2 Diabetes Mellitus: An Open-Label, Multicenter, Randomized, Controlled Study: Hae Jin Kim, In Kyung Jeong, Kyu Yeon Hur, Soo-Kyung Kim, Jung Hyun Noh, Sung Wan Chun, Eun Seok Kang, Eun-Jung Rhee, Sung Hee Choi; Diabetes Metab J. 2022;46(5):689-700. Published online March 17, 2022; DOI: https://doi.org/10.4093/dmj.2021.0183

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Background
The choice of an optimal oral hypoglycemic agent in the initial treatment periods for type 2 diabetes mellitus (T2DM) patients remains difficult and deliberate. We compared the efficacy and safety of glimepiride (GLIM), alogliptin (ALO), and alogliptin-pioglitazone (ALO-PIO) in poorly controlled T2DM patients with drug-naïve or metformin failure.
Methods
In this three-arm, multicenter, open-label, randomized, controlled trial, poorly controlled T2DM patients were randomized to receive GLIM (n=35), ALO (n=31), or ALO-PIO (n=33) therapy for 24 weeks. The primary endpoint was change in the mean glycosylated hemoglobin (HbA1c) levels at week 24 from baseline. Secondary endpoints were changes in HbA1c level at week 12 from baseline, fasting plasma glucose (FPG) levels, lipid profiles at weeks 12 and 24, and parameters of glycemic variability, assessed by continuous glucose monitoring for 24 weeks.
Results
At weeks 12 and 24, the ALO-PIO group showed significant reduction in HbA1c levels compared to the ALO group (–0.96%±0.17% vs. –0.37%±0.17% at week 12; –1.13%±0.19% vs. –0.18%±0.2% at week 24). The ALO-PIO therapy caused greater reduction in FPG levels and significant increase in high-density lipoprotein cholesterol levels at weeks 12 and 24 than the ALO therapy. Compared to low-dose GLIM therapy, ALO-PIO therapy showed greater improvement in glycemic variability. The adverse events were similar among the three arms.
Conclusion
ALO-PIO combination therapy during the early period exerts better glycemic control than ALO monotherapy and excellency in glycemic variability than low-dose sulfonylurea therapy in uncontrolled, drug-naïve or metformin failed T2DM patients.

Citations

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A Comprehensive Review on Weight Loss Associated with Anti-Diabetic Medications
Fatma Haddad, Ghadeer Dokmak, Maryam Bader, Rafik Karaman
Life.2023; 13(4): 1012. CrossRef
Role of Dipeptidyl Peptidase 4 Inhibitors in Antidiabetic Treatment
Ruili Yin, Yongsong Xu, Xin Wang, Longyan Yang, Dong Zhao
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Clinical Care/Education
Factors Associated with Participation in Diabetes Education: The Korea National Health and Nutrition Examination Survey 2007 to 2009: Jung Min Kim, Jae Won Hong, Jung Hyun Noh, Dong-Jun Kim; Diabetes Metab J. 2016;40(6):447-453. Published online September 20, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.6.447

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Background

A recent study revealed that the participation rate in diabetes education among diabetic patients was only about 50% in Korea. We investigated the factors associated with participation in diabetes education.

Methods

The study included 1,255 patients (≥19 years old) diagnosed with diabetes drawn from the total Korea National Health and Nutrition Examination Survey 2007 to 2009 population comprising 30,705 individuals. We compared age, sex, and age- and sex-adjusted clinical characteristics in patients who had received diabetes education versus those who had not.

Results

Of the 1,255 patients, 19.8% (n=248) had received diabetes education. Patients in the group who received diabetes education were younger, diagnosed at an earlier age, had a longer diabetes duration and were more likely to be using insulin therapy compared with the group who did not receive diabetes education (P<0.001). The group who received diabetes education included fewer manual workers (P<0.001) but more college graduates (P=0.004) compared with the group who did not receive diabetes education. Logistic regression analysis revealed that longer diabetes duration increased the likelihood of receiving diabetes education (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.06; P=0.004). Junior high school (OR, 0.47; 95% CI, 0.24 to 0.91; P=0.026) and elementary school education levels (OR, 0.34; 95% CI, 0.17 to 0.65; P=0.001) versus college graduation were inversely correlated with participation in diabetes self-management education. Non-insulin therapy reduced the likelihood of receiving diabetes education (OR, 0.37; 95% CI, 0.21 to 0.64; P<0.001).

Conclusion

Longer diabetes duration, insulin therapy, and higher education level were positively associated with the completion of diabetes education.

Citations

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Management Status of Patients with Type 2 Diabetes Mellitus at General Hospitals in Korea: A 5-Year Follow-Up Study
Jin Hee Jung, Jung Hwa Lee, Hyang Mi Jang, Young Na, Hee Sun Choi, Yeon Hee Lee, Yang Gyo Kang, Na Rae Kim, Jeong Rim Lee, Bok Rye Song, Kang Hee Sim
The Journal of Korean Diabetes.2022; 23(1): 64. CrossRef
Team-based multicomponent care improved and sustained glycaemic control in obese people with type 2 diabetes (T2D) in a Diabetes Centre setting: A quality improvement program with quasi-experimental design
Lee-Ling Lim, Eric S.H. Lau, Risa Ozaki, Tammy T.Y. So, Rebecca Y.M. Wong, Elaine Y.K. Chow, Ronald C.W. Ma, Andrea O.Y. Luk, Juliana C.N. Chan, Alice P.S. Kong
Diabetes Research and Clinical Practice.2022; 194: 110138. CrossRef
Socio-economic determinants of attendance at diabetes self-management education program: using Andersen’s behavioral model
Javad Javan-Noughabi, Seyed Saeed Tabatabaee, Sajad Vahedi, Tahere Sharifi
BMC Health Services Research.2022;[Epub] CrossRef
Sociodemographic Factors Associated with Participation in Diabetes Education among Community-Dwelling Adults with Diabetes
Young-Hoon Lee
Yonsei Medical Journal.2020; 61(2): 169. CrossRef
Influence of health education on clinical parameters in type 2 diabetic subjects with and without hypertension: A longitudinal, comparative analysis in routine primary care settings
Xiu-Jing Hu, Hua-Feng Wu, Yu-Ting Li, Yi Wang, Hui Cheng, Jia-Ji Wang, Bedru H. Mohammed, Isabella Tan, Harry H.X. Wang
Diabetes Research and Clinical Practice.2020; 170: 108539. CrossRef
Disparities in Diabetes Education Program Use by Disability Status Among People with Diabetes: Findings from Behavioral Risk Factor Surveillance System 2015
Junrong Shi, Yong Li
American Journal of Health Education.2019; 50(1): 6. CrossRef
Factors Influencing Preferences of Adults With Type 2 Diabetes for Diabetes Self-Management Education Interventions
Lifeng Fan, Souraya Sidani
Canadian Journal of Diabetes.2018; 42(6): 645. CrossRef
Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 947. CrossRef
Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 337. CrossRef

Brief Report

Glycated Hemoglobin Value for Fasting Plasma Glucose of 126 mg/dL in Korean: The 2011 Korea National Health and Nutrition Examination Survey: Jung Min Kim, Jae Won Hong, Jong Chul Won, Jung Hyun Noh, Kyung Soo Ko, Byoung Doo Rhee, Dong-Jun Kim; Diabetes Metab J. 2014;38(6):480-483. Published online December 15, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.6.480

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We aimed to estimate the cutoff value of glycated hemoglobin (HbA1c, A1c) for fasting plasma glucose (FPG) of 126 mg/dL in the Korean adult population, using the 2011 Korea National Health and Nutrition Examination Survey. A total of 5,421 participants without a history of diabetes and over 19 years of age were included in the analysis. A point-wise area under the receiver operating characteristic curve was used to estimate the optimal A1c cutoff value. A1c threshold of 6.1% produced the highest sum of sensitivity (85.2%) and specificity (90.5%) for FPG of 126 mg/dL (area under the curve, 0.941, P<0.001). A1c of 6.5% produced a sensitivity of 67.7% and specificity of 98.0% for FPG of 126 mg/dL. Considering A1c as one of three criteria for the diagnosis of diabetes and the specificity of an A1c cutoff of 6.5%, the current diagnostic criteria of A1c≥6.5% might be acceptable in the Korean adult population.

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Zeinab Ghasemzadeh Kuchi, Masoomeh Zakerimoghadam, Maryam Esmaeili, Babak Geraiely
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Morning Spot Urine Glucose-to-Creatinine Ratios Predict Overnight Urinary Glucose Excretion in Patients With Type 2 Diabetes
So Ra Kim, Yong-ho Lee, Sang-Guk Lee, Sun Hee Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Jeong-Ho Kim, Byung-Wan Lee
Annals of Laboratory Medicine.2017; 37(1): 9. CrossRef
Glycosylated Hemoglobin Threshold for Predicting Diabetes and Prediabetes from the Fifth Korea National Health and Nutrition Examination Survey
Sangmo Hong, Jun Goo Kang, Chul Sik Kim, Seong Jin Lee, Cheol-Young Park, Chang Beom Lee, Sung-Hee Ihm
Diabetes & Metabolism Journal.2016; 40(2): 167. CrossRef
Is an Oral Glucose Tolerance Test Still Valid for Diagnosing Diabetes Mellitus?
Dong-Lim Kim, Sun-Doo Kim, Suk Kyeong Kim, Sooyoun Park, Kee-Ho Song
Diabetes & Metabolism Journal.2016; 40(2): 118. CrossRef
Comparison of the clinical characteristics of diabetes mellitus diagnosed using fasting plasma glucose and haemoglobin A1c: The 2011 Korea National Health and Nutrition Examination Survey
Sangmo Hong, Jun Goo Kang, Chul Sik Kim, Seong Jin Lee, Chang Beom Lee, Sung-Hee Ihm
Diabetes Research and Clinical Practice.2016; 113: 23. CrossRef
Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331 288 participants
G Danaei, S Fahimi, Y Lu, B Zhou, K Hajifathalian, M Di Cesare, WC Lo, B Reis-Santos, MJ Cowan, JE Shaw, J Bentham, JK Lin, H Bixby, D Magliano, P Bovet, JJ Miranda, YH Khang, GA Stevens, LM Riley, MK Ali, M Ezzati, ZA Abdeen, KA Kadir, M Abu-Rmeileh, B A
The Lancet Diabetes & Endocrinology.2015; 3(8): 624. CrossRef
The Optimal Cutoff Value of Glycated Hemoglobin for Detection of Diabetic Retinopathy
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Original Articles

Factors Associated for Mild Cognitive Impairment in Older Korean Adults with Type 2 Diabetes Mellitus: Yun Jeong Lee, Hye Mi Kang, Na Kyung Kim, Ju Yeon Yang, Jung Hyun Noh, Kyung Soo Ko, Byoung Doo Rhee, Dong-Jun Kim; Diabetes Metab J. 2014;38(2):150-157. Published online April 18, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.2.150

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Background

The aim of this study was to identify factors associated with mild cognitive impairment (MCI) in older Korean adults with type 2 diabetes mellitus.

Methods

A total of 226 older (age ≥65 years) adults without a history of cerebrovascular disease or dementia participated in this study. Cognitive function was assessed with the Montreal Cognitive Assessment-Korean version (MoCA-K). A MoCA-K score <23 was defined as MCI.

Results

The prevalence of MCI was 32.7%. In a logistic regression analysis, age (≥74 years old vs. 65-68 years old; odds ratio [OR], 3.69; 95% confidence interval [CI], 1.55 to 8.82; P=0.003), educational background (college graduation vs. no school or elementary school graduation; OR, 0.16; 95% CI, 0.05 to 0.46; P=0.001), and systolic blood pressure (≥135 mm Hg vs. ≤120 mm Hg; OR, 3.25; 95% CI, 1.29 to 8.17; P=0.012) were associated with MCI.

Conclusion

More concentrated efforts focused on early detection and appropriate management of MCI may be required in older Korean adults with type 2 diabetes mellitus.

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Risk Factors Associated with Left Ventricular Diastolic Dysfunction in Type 2 Diabetic Patients without Hypertension: Jung Hyun Noh, Joon Hyung Doh, Sung Yun Lee, Tae Nyun Kim, Hyuk Lee, Hwa Young Song, Jeong Hyun Park, Kyung Soo Ko, Byoung Doo Rhee, Dong Jun Kim; Korean Diabetes J. 2010;34(1):40-46. Published online February 28, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.1.40

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Background

Hypertension and age are recognized as important risk factors for left ventricular (LV) diastolic dysfunction. Some studies have shown that diabetes itself may also be an independent risk factor for LV diastolic dysfunction, although this is controversial. The aim of this study was to determine the factors associated with LV diastolic dysfunction in patients with type 2 diabetes in the absence of hypertension or ischemic heart disease (IHD).

Methods

Participants in this study consisted of 65 type 2 diabetes patients (M : F = 45 : 20; mean age 51 [26 to 76] years; mean body mass index [BMI] 25.0 ± 2.5 kg/m²) without hypertension, heart disease, or renal disease. Individuals with ischemic electrocardiographic changes were excluded. LV diastolic function was evaluated by Doppler echocardiographic studies.

Results

Fifteen patients (23.1%) showed LV diastolic dysfunction on Doppler echocardiographic studies. Patients with LV diastolic dysfunction were older than those without diastolic dysfunction (60.0 ± 2.5 vs. 50.5 ± 1.9 years; P < 0.01). After adjusting for age and sex, BMI was higher (26.6 ± 0.7 vs. 24.6 ± 0.3 kg/m²; P < 0.01) and diabetes duration was longer (9.65 ± 1.48 vs. 4.71 ± 0.78 years; P < 0.01) in patients with LV diastolic dysfunction than in those without diastolic dysfunction. There were no differences in sex, smoking, blood pressure, lipid profiles, hemoglobin A₁C, fasting glucose, fasting insulin, or diabetic microvascular complications between the LV diastolic dysfunction group and the normal diastolic function group. After adjusting for age, sex, and BMI, diabetes duration was found to be independently associated with LV diastolic dysfunction (odds ratio 1.38; confidence interval 1.12 to 1.72; P = 0.003).

Conclusion

These results suggest that diabetes duration may be a risk factor for LV diastolic dysfunction in type 2 diabetic patients without hypertension or IHD.

Citations

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Glycemic variability is associated with diastolic dysfunction in patients with type 2 diabetes
Yana Dzhun, Georgy Mankovsky, Nadiya Rudenko, Yevgen Marushko, Yanina Saienko, Borys Mankovsky
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Editorials

Vitamin D and Diabetes Mellitus.: Jung Hyun Noh; Korean Diabetes J. 2009;33(4):276-278. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.276

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Abstract PDF: No abstract available.

Serum Bilirubin and Coronary Artery Disease.: Jung Hyun Noh; Korean Diabetes J. 2008;32(4):301-303. Published online August 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.4.301

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Abstract PDF: No abstract available.

Original Articles

Thiazolidinediones on Insulin Resistance and Insulin Secretion in Obese Diabetic OLETF Rats.: Jung hyun Noh, Seung hyun Hong, Kyoung hee Lee, Kyoung Min Min, Tae young Yang, Myung shik Lee, Kwang won Kim, Moon kyu Lee; Korean Diabetes J. 2007;31(1):33-43. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.33

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Abstract PDF: BACKGROUND
Thiazolidinediones are synthetic peroxisome proliferator-activated receptor-gamma agonists that decrease insulin resistance but, as in vitro and in vivo studies suggest, may have direct beneficial effects on pancreatic beta cells. Here, we investigated the effects of thiazolidinediones (TZDs) on the insulin resistance, beta-cell mass and insulin secretion in obese diabetic OLETF rats. METHODS: We studied insulin resistance (by hyperinsulinemic euglycemic clamp) and insulin secretion (by hyperglycemic clamp) in TZDs administered OLETF and LETO rats. Histologic alterations of the islets were observed and beta-cell mass was also measured by point counting method. RESULTS: Chronic administration of troglitazone (TGZ, 0.15%) or pioglitazone (PGZ, 0.02%) prevented the development of glucose intolerance in OLETF rats, as assessed by oral glucose tolerance test. There was significant difference in submaximal glucose infusion rate between TGZ-treated and untreated OLETF rats during euglycemic clamp studies at 24 weeks of age. At 16 and 24 weeks of ages, beta-cell mass significantly increased in TGZ-treated OLETF rats compared to untreated animals. At 19 weeks and 30 weeks of age, first-phase insulin secretion was not different in PGZ-treated OLETF rats from untreated OLETF rats during hyperglycemic clamp study. At 30 weeks of age, late-phase insulin secretion was decreased in PGZ-treated OLETF rats compared to untreated OLETF rats. The expression of alpha-smooth muscle actin, a marker of activated pancreatic stellate cells that are involved in the fibrosis of the pancreas, in the islets was suppressed by TGZ treatment at 24 weeks of age. CONCLUSION: The treatment of TGZ prevented the development of diabetes, and increased insulin sensitivity and pancreatic beta-cell mass in OLETF rats. These results might be related with the suppression of pancreatic stellate cells. Insulin secretion was not affected by PGZ treatment.

Serum Adiponectin, TNF-alpha, IL-6 and Insulin Resistance in Women with Polycystic Ovary Syndrome.: Young A Kim, Jung Hyun Noh, Dong Jun Kim, Tae Hyun Um, Chong Rae Cho, Na young Jang, Soo Kyung Kwon, Soon Hee Lee, Jeong Hyun Park, Kyung Soo Ko, Byoung Doo Rhee, Kyung Ho Lim; Korean Diabetes J. 2006;30(2):104-111. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.104

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Abstract PDF

BACKGROUND
To determine plasma adipokines such as adiponectin, IL-6 and TNF-alpha concentrations in women with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adipocytokines to the hormonal and metabolic parameters, including measures of insulin resistance (IR). METHODS: Forty-four selected women were classified as follows: 13 obese (body mass index [BMI] > or = 25 kg/m(2)) with PCOS; 15 non-obese (BMI < 25 kg/m(2)) with PCOS; 8 obese without PCOS, and 8 non-obese without PCOS. Blood samples were collected from all women with or without PCOS after an overnight fast. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, 17-alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), insulin, glucose, adiponectin, TNF-alpha and IL-6 were measured. Measures of IR included HOMA-IR and QUICKI. RESULTS: In non-obese group, fasting insulin levels and HOMA-IR in PCOS were significantly higher compared to control. However, Adiponectin, TNF-alpha and IL-6 concentrations were found not to be different in obese women with PCOS as compared with obese women without PCOS and in non-obese women with PCOS as compared with non-obese women without PCOS. Adiponectin concentrations correlated inversely with BMI, waist circumference (WC), total fat mass, serum insulin, and HOMA-IR in PCOS group. However, multiple regression analysis showed that BMI was the only independent determinant of adiponectin concentration. CONCLUSION: Our results suggest that insulin sensitivity per se probably does not play any role in the control of adipokines levels such as adiponectin, TNF-alpha and IL-6 in PCOS women

Citations

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Adiponectin in Women with Polycystic Ovary Syndrome
Hyun-Young Shin, Duk-Chul Lee, Ji-Won Lee
Korean Journal of Family Medicine.2011; 32(4): 243. CrossRef

Effect of Pancreatic Islet Autotransplantation after Pacreatectomy in Patients with Benign Pancreatic Tumor.: Jae Hwan Jee, Byung Wan Lee, Seung Hoon Oh, Ji Youn Kim, Hyun Jin Kim, Jung Hyun Noh, Sung Ho Choi, Jae Hoon Chung, Yong Ki Min, Myung Sik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2004;28(2):88-100. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Previously, in patients suffering from insulin deficient DM after a partial or total pancreatectomy as treatment for a benign pancreatic tumor, insulin treatment has only led to severe fluctuation in the blood glucose level, and frequently to sudden hypoglycemia due to glucagon deficiency and lack of delicate insulin control. Several worldwide reports have suggested that autologous transplantation of islet cells isolated from an unaffected portion of a resected pancreas, mostly for the cure of chronic pancreatitis or a pancreatic tumor without immunosuppressive agent treatment, resulted in good glycemic control, and even in the prevention of DM. Attempts were made to evaluate the effect of islet autotrans-plantation for glycemic control in eight patients undergoing a pancreatectomy for a benign pancreatic tumor. METHOD: Between December 2001 and October 2003, an islet autotransplantation was performed in eight patients patholologically confirmed with benign pancreatic tumors following a pancreatectomy. There was no past medical history of DM in any of the patients, but impaired glucose tolerance(IGT) was detected in 2 patients on a 75g oral glucose tolerance test(oral GTT), and was also suspected in a pre-pancreatectomy state patient. Islets were isolated by ductal perfusion, using the cold collagenase P and semi-automated method, and purified on a density gradients using a COBE 2991 cell processor or tube system of Ficoll solution. After being confirmed as a benign pancreatic tumor, the cultured islet cells were transplanted to the liver through the portal vein. Each patient was transplanted with a mean islet mass of 3,190+/-896 islet equivalents per kilogram of body weight. The median follow-up period was 12 months, with the longest being 36 months. All patients underwent follow-up for oral GTT, HbA1c and complication of DM, pancreatectomy, or transplantation within this period. RESULTS: On the 75g oral GTT, a normal glucose tolerance(NGT) was maintained until the last follow-up month in five of the eight patients undergoing islet autotransplantation. DM recurred in three of the eight patients undergoing islet autotransplantation, with to cases in a state of IGT and 1 case of NGT at the initial stage. The HbA1c levels were not significantly changed between pre-pancreatectomy and post-islet transplantation period. The amplitude of the decrease in the postprandial 2 hour glucose level was larger than that of the fasting glucose level between the pre- and post-transplantation periods, but this was not statistically. Also, the elevation of the postprandial C-peptide level was larger than the fasting C-peptide during the post-transplantation period, but again, this was not significant. No complications occurred in relation with the islet transplantation, portography, DM and hypoglycemia. CONCLUSION: Islet transplantation could prevent and reverse the diabetic process in patients undergoing a pancreatectomy for a benign pancreatic tumor, with some exception such as those with a small transplanted islet mass or with initial insulin resistance. The 2 hour postprandial changes in the glucose and C- peptide levels on the oral GTT somewhat reflected insulin secretory function of the remaining and newly transplanted islet cells. Pancreatic islet autotransplantation is the most prospective method for the prevention or cure of insulin deficient DM following a pancreatectomy for a benign pancreatic tumor.

Effects of Peroxisome Proliferator-activated Receptor-gamma(PPARgamma) on the Pancreatic beta Cell Proliferation.: Jung Hyun Noh, Tae Young Yang, In Kyung Jeong, Jae Hun Chung, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee; Korean Diabetes J. 2003;27(3):241-252. Published online June 1, 2003

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Abstract PDF: BACKGROUND
The effects and mechanisms of PPARgamma ligands on the cell proliferation in pancreatic beta cells were examined. METHODS: PPARgamma 1 cDNA was overexpressed in INS-1 cells using an adenoviral vector. The cell proliferations were measured by the MTT assay method, following the treatments with troglitazone (TGZ), rosiglitazone (RGZ), 15d-prostaglandin J2 (15d-PGJ2) or retinoic acid (RA), at increasing doses, in INS-1 and PPARgamma overexpressed INS-1 cells. The apoptosis, telomere length and cell cycles were determined after the PPARgamma ligand treatment. RESULTS: The long-term incubation, with PPARgamma ligands over 24 hr, inhibited the INS-1 cell proliferation rate. Apoptosis was not observed with the PPARgamma ligand treatment. G1 cell cycle arrest was observed with the troglitazone treatment. The telomere length remained unchanged following the TGZ treatment. The basal cell proliferation rate was unaffected by the overexpression of PPARgamma . After 48 h of TGZ treatment, the proliferation of the INS-1 cells was inhibited, in a dose- dependent manner, both with and without the overexpression. Moreover, the degree of inhibition was exaggerated in the PPARgamma overexpressed cells compared to beta gal overexpressed cells. CONCLUSION: PPARgamma ligands have direct inhibitory effects on the proliferation of INS-1 cells. Although the basal cell proliferation rate was not affected by PPARgamma overexpression, the PPARgamma overexpression and PPARgamma ligands have a synergistic inhibitory effect on the cell proliferation rate in pancreatic beta cells. G1 cell cycle arrest may be involved in the reduction of cell proliferation due to PPARgamma ligands.

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