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

 Sung Hee Choi  ;  Zheng Shan Zhao  ;  Bong Soo Cha  ;  Hyun Chul Lee  ;  Sung Kil Lim  ;  Chul Woo Ahn  ;  Dae Jung Kim  ;  Soo Kyung Kim  ;  Yong Jik Lee 
 Diabetes-Metabolism Research and Reviews, Vol.23(5) : 411-418, 2007 
Journal Title
 Diabetes-Metabolism Research and Reviews 
Issue Date
Animals ; Diabetes Mellitus, Type 2/prevention & control* ; Disease Models, Animal ; Hypoglycemic Agents/therapeutic use ; Metformin/therapeutic use ; Pioglitazone ; Prediabetic State/drug therapy ; Rats ; Rats, Inbred OLETF ; Thiazolidinediones/therapeutic use ; Weight Gain/drug effects ; Weight Loss/drug effects
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.
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1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Chul Woo(안철우) ORCID logo https://orcid.org/0000-0003-3733-7486
Lee, Yong Jik(이용직)
Lee, Hyun Chul(이현철)
Lim, Sung Kil(임승길)
Zhao, Zheng Shan(조정산)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
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