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

Sung Hee Choi, Zheng Shan Zhao, Yong Jik Lee, Soo Kyung Kim, Dae Jung Kim, Chul Woo Ahn, Sungkil Lim, Hyun Chul Lee, Bong Soo Cha

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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/1 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.

Original languageEnglish
Pages (from-to)411-418
Number of pages8
JournalDiabetes/Metabolism Research and Reviews
Volume23
Issue number5
DOIs
Publication statusPublished - 2007 Jul 1

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pioglitazone
Inbred OLETF Rats
Type 2 Diabetes Mellitus
Metformin
Insulin
Glucose
Weight Gain
Pancreas
Triglycerides
Fats
Subcutaneous Fat
Dyslipidemias
Islets of Langerhans
Insulin Resistance
Weight Loss
Fasting
Body Weight

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Choi, S. H., Zhao, Z. S., Lee, Y. J., Kim, S. K., Kim, D. J., Ahn, C. W., ... Cha, B. S. (2007). The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats. Diabetes/Metabolism Research and Reviews, 23(5), 411-418. https://doi.org/10.1002/dmrr.756
Choi, Sung Hee ; Zhao, Zheng Shan ; Lee, Yong Jik ; Kim, Soo Kyung ; Kim, Dae Jung ; Ahn, Chul Woo ; Lim, Sungkil ; Lee, Hyun Chul ; Cha, Bong Soo. / The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats. In: Diabetes/Metabolism Research and Reviews. 2007 ; Vol. 23, No. 5. pp. 411-418.
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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/1 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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Choi, SH, Zhao, ZS, Lee, YJ, Kim, SK, Kim, DJ, Ahn, CW, Lim, S, Lee, HC & Cha, BS 2007, 'The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats', Diabetes/Metabolism Research and Reviews, vol. 23, no. 5, pp. 411-418. https://doi.org/10.1002/dmrr.756

The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats. / Choi, Sung Hee; Zhao, Zheng Shan; Lee, Yong Jik; Kim, Soo Kyung; Kim, Dae Jung; Ahn, Chul Woo; Lim, Sungkil; Lee, Hyun Chul; Cha, Bong Soo.

In: Diabetes/Metabolism Research and Reviews, Vol. 23, No. 5, 01.07.2007, p. 411-418.

Research output: Contribution to journalArticle

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T1 - The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats

AU - Choi, Sung Hee

AU - Zhao, Zheng Shan

AU - Lee, Yong Jik

AU - Kim, Soo Kyung

AU - Kim, Dae Jung

AU - Ahn, Chul Woo

AU - Lim, Sungkil

AU - Lee, Hyun Chul

AU - Cha, Bong Soo

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N2 - 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/1 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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