Diabetes & Metabolism Journal

Original Articles

Association Study of the Peroxisome Proliferators-Activated Receptor gamma2 Pro12Ala Polymorphism with Diabetic Nephropathy.: Kyu Ho Lee, Hee Seog Jeong, Khan Young Choi, Hyun Kim, Dal Sic Lee, Ji Young Kang, Hyun Jeong Jeon, Tae Keun Oh; Korean Diabetes J. 2008;32(5):402-408. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.402

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Abstract PDF: BACKGROUND
Peroxisome proliferators-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and known to play a role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The PPARgamma2 Pro12Ala polymorphism has recently been shown to be associated with diabetic nephropathy. In this study, we evaluated the relationship between PPARgamma2 Pro12Ala polymorphism and type 2 diabetic nephropathy whose duration of diabetes was over 10 years. METHODS: We conducted a case-control study, which enrolled 367 patients with type 2 diabetes. Genotyping of PPARgamma2 Pro12Ala polymorphism was performed using polymerase chain reaction followed by digestion with Hae III restriction enzyme. RESULTS: The genotype or allele frequencies of PPARgamma2 Pro12Ala polymorphism were not significantly different in diabetic patients with or without diabetic nephropathy. The genotype frequencies in terms of diabetic retinopathy and macrovascular complications such as coronary artery disease or stroke were not different either. Interestingly, nephropathy patients with Ala/Pro genotype showed lower C-peptide levels than those of Pro/Pro genotype. CONCLUSION: Our results suggest that PPARgamma2 Pro12Ala polymorphism is not associated with diabetic nephropathy in type 2 diabetic patients.

Association of Kir6.2 and Peroxisome Proliferator-activated Receptor-gamma (PPARgamma) Polymorphisms with Type 2 Diabetes in Koreans.: Jung Eun Lee, Su Won Kim, Hyun Ae Seo, Jae Han Jeon, Seong Su Moon, Hee Kyung Kim, Yun Jeong Doh, Bo Wan Kim, Jung Guk Kim, Min Yoo, In Kyu Lee; Korean Diabetes J. 2007;31(6):455-464. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.455

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Abstract PDF: BACKGROUND
The type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. Several variants may contribute significantly to the risk of type 2 diabetes conferring insulin resistance of liver, muscle and fat (Pro12Ala) and a relative insulin secretory deficiency (Glu23Lys). In this study, we evaluated the association of Pro12Ala variant of the peroxisome proliferator- activated receptor-gamma and the Glu23Lys variant of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11) with the type 2 diabetes in Korean population. METHOD: This study included 331 subjects consisting of 172 patients with type 2 diabetes and 159 non- diabetic control subjects enrolled from the Kyungpook, Keimyung and Catholic university hospital in Daegu, Korea. We genotyped Kir6.2 (Glu23Lys) and PPARgamma (Pro12Ala) polymorphism and examined their association with the type 2 diabetes. RESULT: In the separate analyses, the Kir6.2 Glu23Lys (P = 0.385) and the PPARgamma Pro12Ala (P = 0.191) polymorphism showed no significant association with type 2 diabetes. In addition, the results of our study showed no evidence of a synergistic interaction between Kir6.2 and PPARgamma gene in each group (P = 0.110, P = 0.276). CONCLUSION: In this study, no association was seen between the genetic polymorphisms of Kir6.2, PPARgamma and type 2 diabetes. However, to clarify whether genetic polymorphisms of these genes contribute to the development of type 2 diabetes, further studies involving larger Korean populations may be needed.

Effects of Caloric Restriction on the Expression of PGC-1 and PPARs mRNA in Liver of Otsuka Long-Evans Tokushima Fatty Rats.: Sang Yong Kim, Jin Hwa Kim, Hak Yeon Bae, Byoung Rai Lee; Korean Diabetes J. 2006;30(3):161-169. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.161

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Abstract PDF: BACKGROUND
Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. PPARgamma-coactivator 1 (PGC-1) and Peroxisome proliferator -activated receptors (PPARs) costimulate the expression of key enzymes of gluconeogenetic pathway. This study was performed to evaluate the response to dietary caloric restriction (CR) on the PPARs and PGC-1 expression in liver of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Diabetic OLETF rats (male, 24 weeks) and Long-Evans Tokushima Otsuka (LETO) rats (male, 24 weeks) were used in this study. Liver PPARs and PGC-1 mRNA, and blood glucose levels were investigated at 1, 2, and 3 weeks after the beginning of 30% CR. PPARs and PGC-1 mRNA were determined by RT-PCR and blood glucose levels were measured by spectrophotometric assay. RESULTS: The liver PGC-1 mRNA expressions were increased to 19% in non-diabetic LETO rats but significant change was not observed in diabetic OLETF rats by 30% CR. The liver PPARgamma mRNA expressions were not changed in non-diabetic LETO rats but increased to 23% in diabetic OLETF rats by 30% CR. The difference of PPARalpha and PPARbeta mRNA expressions in liver of OLETF and LETO rats were not observed. CONCLUSION: The liver PPARgamma and PGC-1 expression response to CR are altered in OLETF rats compared to in LETO rats. These findings suggested that PPARgamma and PGC-1 expression control system altered in diabetic OLETF rat liver and altered PPARgamma and PCG-1 expression may some roles on the aberrantly activated gluconeogenesis in diabetes mellitus.

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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