Effects of troglitazone on skeletal muscle and liver protein tyrosine phosphatase activity in insulin-resistant Otsuka Long-Evans Tokushima Fatty rats

摘要

Background: Protein tyrosine phosphatases (PTPases) appear to play an essential role in the regulation of steady-state phosphorylation of the insulin receptor and other proteins in the insulin-signaling pathway. Objectives: This study determined the role of PTPases in skeletal muscle and liver in an insulin-resistant model and the in vivo effect of troglitazone on PTPases. Methods: We used 26-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats as models of insulin resistance. PTPase activity was assessed with reduced carboxyamido-methylated and -maleylated lysozyme as substrates. The protein levels of 3 major candidate PTPases - leukocyte common antigen-related PTPase (LAR), PTPase 1B (PTP1B), and src homology 2-containing PTPase (SH-PTP2) - in skeletal muscle and liver of OLETF rats were analyzed using Western blot. The activities and amounts of PTPases in skeletal muscle and liver of OLETF rats treated with troglitazone for 7 days also were examined. Results: Particulate and cytosolic PTPaseactivities in skeletal muscle of OLETF rats were increased compared with those in control rats. Similar changes were observed in the liver. The protein levels of LAR, PTP1B, and SH-PTP2 in particulate fractions of skeletal muscle of OLETF rats were increased, but levels of PTP1B and SH-PTP2 in cytosolic fractions were unchanged. Similar findings were observed in the liver. Troglitazone normalized the increased PTPase activity and each protein level except cytosolic fraction of the liver. Conclusions: The findings suggest that troglitazone decreases elevated activities and levels of PTPases in the particulate fraction of the skeletal muscle and liver of OLETF rats, and that PTPase plays important roles through regulating the insulin-signaling system in the pathogenesis of insulin resistance in OLETF rats.