Abstract
Insulin stimulates glucose uptake by adipocytes, whereas TNFα impairs this insulin sensitivity thereby inducing insulin resistance in the cells. Since insulin and TNFα have been shown to induce cell swelling and shrinkage, respectively, in many other cell types, there is a possibility that a change of cell volume serves as a signal for insulin sensitivity and insulin resistance in adipocytes. To test this possibility, the present study was performed in 3T3-L1 adipocytes. Cell size measurements showed that insulin induced swelling and this insulin-induced swelling was inhibited by addition of a blocker of Na+/H+ exchanger, amiloride, or that of anion exchanger, DIDS. Amiloride or DIDS also inhibited insulin-induced translocation of GLUT4 to the plasma membrane and glucose uptake. TNFα suppressed insulin-induced GLUT4 translocation, glucose uptake and cell swelling, and these TNFα effects were inhibited by a Cl− channel blocker, NPPB or glibenclamide. Whole-cell patch clamp studies demonstrated that TNFα activated volume-sensitive outwardly rectifying (VSOR) Cl− currents. TNFα also induced cell shrinkage in a manner sensitive to NPPB or glibenclamide. Taken together, it appears that cell volume changes are involved in the mechanisms of insulin sensitivity and TNFα-induced insulin resistance in adipocytes. [J Physiol Sci. 2008;58 Suppl:S208]
