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- Abstract - - Abstract - - Abstract - - Abstract - Background The regulation of tyrosine phosphorylation/dephosphorylation is an important mechanism in various intracellular metabolism. Also impaired insulin signal transduction is important in pathogenesis of type 2 diabetes. It has been reported that PTP1B is a negative regulator of insulin action, and G iα2-protein is related to the regulation of PTP1B. Herein we investigated the long-term effects of ramipril on PTP1B/insulin signal protein interaction and the relation between G iα2 and PTP1B in animal model of type 2 diabetes (OLETF rat). Methods OLETF rats and age-matched LETO rats were divided into two groups. One group of rats received ramipril (10 mg/kg body weight) for 12 weeks, and another group did not. Finally, each group was divided into 2 subgroups, with or without insulin injection intravenously, before sacrifice. After sacrifice, tissues extracts of liver, hind limb muscle, and epididymal fat were obtained for quantification of PTP1B, Giα2, and several insulin signal proteins by western blotting. Results: In liver and muscle, the levels of basal PTP1B and activated PTP1B of OLETF rats treated with ramipril and insulin were significantly decreased. The levels of G iα2, activated IRS-2, and activated p-85 α were significantly increased in OLETF rats treated with ramipril and insulin. In adipose tissue, the levels of G iα2 and activated p-85 α of OLETF rats treated with ramipril and insulin were slightly increased as in liver and muscle. But, the levels of basal PTP1B and activated PTP1B were significantly increased. And, the levels of activated IRS-1 and activated IRS-2 were decreased. Conclusion: These results suggest that the improvement of insulin sensitivity by treatment with ramipril was related to the decreased level of activated PTP1B. Also, we could suggest that the changes of activated PTP1B level was related with the changes of G iα 2-protein. However, the results of adipose tissue were different from those of liver and muscle. So it seemed likely that there would be various major modulators for regulation of insulin signal pathway according to tissue (J Kor Diabetes Assoc 30:25~38, 2006).

The long-term effect of ramipril on Giα2-protein and Protein Tyrosine Phosphatase 1B in an animal model of type 2 diabetes(OLETF rat)