APPS November 2002 Meeting Abstract 2409


G.D. Wadley1, C. Bruce2, N. Konstantopoulos3, L. Macauley3, J. Hawley2, M. Hargreaves1, K. Howlett1, D. Cameron-Smith1, 1 School of Health Sciences, Deakin University, Burwood, Victoria, School of Medical Sciences, RMIT University, Bundoora, Victoria, 3 Health Sciences and Nutrition, CSIRO, Parkville, Victoria.

Very recently, a second novel insulin-signalling pathway involving the recruitment of the protein Cbl to the insulin receptor (IR) and has been shown in 3T3-L1 adipocytes to be a necessary step for insulin stimulated GLUT4 translocation1. It is unknown if Cbl plays a role in exercise-mediated activation of GLUT4, indeed the activation of this pathway by insulin has yet to be reported in mammalian tissue, let alone skeletal muscle. In the present study, we hypothesised that exercise alone does not activate Cbl, but that following insulin stimulation this pathway is activated in rodent skeletal muscle. Furthermore, since obese Zucker rats have insulin resistant skeletal muscle we also hypothesised that the insulin activation of Cbl is downregulated when compared to lean controls. Lean and obese zucker rats (n=18, each group) were assigned to one of three treatments; 1) sedentary, 2) exercised (swimming for 4 hours) and 3) IP supraphysiological dose of insulin for 5 minutes. Immunoprecipitation of skeletal muscle lysates with appropriate antibodies revealed both a significant increase in Cbl protein abundance and IR phosphorylation following supraphysiological insulin stimulation, but not following exercise. Furthermore, following insulin stimulation, the IR phosphorylation of obese rats was significantly lower than lean rats, however Cbl protein abundance was not significantly different in lean versus obese rats. These results show for the first time an effect of insulin on Cbl protein abundance in skeletal muscle and future work should examine if Cbl is phosphorylated by insulin in skeletal muscle.

(1) Baumann C, Ribon V,Kanzaki M, Thurmond D, Mora S, Shigematsu S, Bickel P, Pessin J, Saltiel A. Nature. 2000;407(14):202-207.

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