Elevation in Tanis Expression Alters Glucose Metabolism and Insulin Sensitivity in H4IIE Cells

Y. Gao, K. Walder, T. Sunderland, L. Kantham, H. C. Feng, M. Quick, N. Bishara, A. de Silva, G. Augert, J. Tenne-Brown, G. R. Collier
2003 Diabetes  
Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein
more » ... luble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver. Diabetes 52:929 -934, 2003 RESEARCH DESIGN AND METHODS Experimental animals. The use of all animals in this study was approved by Deakin University Animal Ethics Committee. A colony of P. obesus was maintained as previously described (14) . Animals were given a standard laboratory diet, from which 12% of energy was derived from fat, 63% was derived from carbohydrate, and 25% was derived from protein (Barastoc, Pakenham, Australia). Under such conditions, a proportion of the animals developed obesity and diabetes. At 16 weeks of age, whole blood glucose and plasma insulin concentrations were determined using an automated glucose analyzer and radioimmunoassay, respectively (14) .
doi:10.2337/diabetes.52.4.929 pmid:12663463 fatcat:6schh4a7zvdjnolkidzgq67whq