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


CONCLUSIONS
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.
Choi
Sung Hee
SH
Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Bundang Hospital, Seongnam, Korea.
Zhao
Zheng Shan
ZS
Lee
Yong Jik
YJ
Kim
Soo Kyung
SK
Kim
Dae Jung
DJ
Ahn
Chul Woo
CW
Lim
Sung Kil
SK
Lee
Hyun Chul
HC
Cha
Bong Soo
BS
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D000077205:Pioglitazone; D011236:Prediabetic State / Q000188:drug therapy; D051381:Rats; D020334:Rats, Inbred OLETF; D045162:Thiazolidinediones / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; D000077205:Pioglitazone