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

Authors
Choi, SH; Zhao, ZS; Lee, YJ; Kim, SK; Kim, DJ; Ahn, CW; Lim, SK; Lee, HC; Cha, BS
Citation
Diabetes/metabolism research and reviews, 23(5):411-418, 2007
Journal Title
Diabetes/metabolism research and reviews
ISSN
1520-75521520-7560
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.
MeSH terms
AnimalsDiabetes Mellitus, Type 2/prevention & control*Disease Models, AnimalHypoglycemic Agents/therapeutic useMetformin/therapeutic usePrediabetic State/drug therapyRatsRats, Inbred OLETFThiazolidinediones/therapeutic useWeight Gain/drug effectsWeight Loss/drug effects
DOI
10.1002/dmrr.756
PMID
17538941
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
AJOU Authors
김, 대중
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