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Biochemical and Molecular Actions of Nutrients

Soluble Fibroin Enhances Insulin Sensitivity and Glucose Metabolism in 3T3-L1 Adipocytes^1,2

School of Bioscience and Food Technology, Handong Global University, Pohang, South Korea and ^* Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL

³To whom correspondence should be addressed. E-mail: sfrost{at}ufl.edu.

Type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features of insulin resistance. In vivo treatment of ob/ob mice with hydrolyzed fibroin reverses these pathological attributes. To explore the mechanism underlying this effect, we used the murine, 3T3-L1 adipocyte cell line, which has been used extensively to model adipocyte function. Chronic exposure of 3T3-L1 adipocytes to insulin leads to a 50% loss of insulin-stimulated glucose uptake. Chronic exposure to different preparations of fibroin partially blocked the response to insulin but also increased the sensitivity of control cells to the acute action of insulin. The latter effect was most robust at physiologic concentrations of insulin. Fibroin did not prevent the insulin-induced downregulation of the insulin receptor or the tyrosine kinase activity associated with the receptor. Further, fibroin had no effect on the activity of the insulin-sensitive downstream kinase, Akt. Interestingly, fibroin accelerated glucose metabolism and glycogen turnover independent of insulin action. In addition, fibroin upregulated glucose transporter (GLUT)1, which increased its expression at the cell surface and enhanced GLUT4 translocation. Together, these phenomena may underlie the improvement in diabetic hyperglycemia noted in vivo in response to fibroin.

KEY WORDS: • insulin resistance • 3T3-L1 adipocytes • GLUT1 • GLUT4 • fibroin