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The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats

Cited 18 time in Web of Science Cited 18 time in Scopus
Authors
Choi, Sung Hee; Zhao, Zheng Shan; Lee, Yong Jik; Kim, Soo Kyung; Kim, Dae Jung; Ahn, Chul Woo; Lim, Sung Kil; Lee, Hyun Chul; Cha, Bong Soo
Issue Date
2007-06-01
Publisher
Wiley-Blackwell
Citation
Diabetes Metab Res Rev. 2007 Jul;23(5):411-8.
Keywords
AnimalsDiabetes Mellitus, Type 2/*prevention & controlDisease Models, AnimalHypoglycemic Agents/therapeutic useMetformin/therapeutic usePrediabetic State/drug therapyRatsRats, Inbred OLETFThiazolidinediones/therapeutic useWeight Gain/drug effectsWeight Loss/drug effects
Abstract
OBJECTIVE: To investigate the effects of pioglitazone and metformin treatment during pre-diabetic period for the prevention of diabetes in a rat model. METHODS: OLETF rats aged 18-weeks, were treated with pioglitazone (10 mg/kg/day) and metformin (300 mg/kg/day) for 10 weeks from their pre-diabetic period. We measured weight, lipid profiles, fat distribution, glucose tolerance, and pancreatic insulin content. RESULTS: Prominent weight gain (mostly subcutaneous fat area) was observed in the pioglitazone-treated OLETF (O-P) rats versus significant weight loss was observed in the metformin-treated OLETF (O-M) rats. Pioglitazone reversed the serum triglyceride (TG) and FFAs levels to normal (TG 0.46 +/- 0.04 vs 0.88 +/- 0.05 mmol/l in LETO). At the age of 28 weeks, the O-P rats showed completely normal glucose tolerance, and the glucose disposal rate (GDR) was markedly improved (25.6 +/- 0.4 vs 20.6 +/- 0.5 mg/min/kg in O-C, p < 0.05). The O-M rats also showed an improved fasting glucose and GDR level, but not as much as those with O-P rats. The pancreas insulin contents were much improved in the O-P rats (22.9 +/- 1.2 vs 18.8 +/- 1.3 nmol/pancreas in O-M rats, p < 0.05) with histological improvement. CONCLUSION: The pre-diabetic treatment with pioglitazone, despite significant weight gain, completely prevents to develop diabetes and enhances beta cell function with preservation of islet cell changes. Metformin treatment was also effective, but mainly by ameliorating the insulin resistance with marked reduction in body weight. The reversal of dyslipidaemia and the fat redistribution might contribute to the greater improvement of pioglitazone treatment compared to metformin in OLETF rats.
ISSN
1520-7552 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17538941

http://hdl.handle.net/10371/24723
DOI
https://doi.org/10.1002/dmrr.756
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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