Role of Ca<SUP>2&#8290;</SUP> in the Stimulation of Glucose Transport by Insulin in Adipocytes

Role of Ca<SUP>2&#8290;</SUP> in the Stimulation of Glucose Transport by Insulin in Adipocytes

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<P> We investigated the role of Ca<SUP>2&#8290;</SUP> and protein kinases/phosphatases in the stimulatory effect of insulin on glucose transport. In isolated rat adipocytes, the simple omission of CaCl<SUB>2</SUB> from the incubation medium significantly reduced, but did not abolish, insulin-stimulated 2-deoxy glucose (2-DG) uptake. Pre-loading adipocytes with intracellular Ca<SUP>2&#8290;</SUP> chelator, 5,5 -dimethyl bis (<I>o</I>-aminophenoxy)ethane-N,N,N N tetraacetic acetoxymethyl ester (5,5 -dimethyl BAPTA/AM) completely blocked the stimulation. Insulin raised intracellular Ca<SUP>2&#8290;</SUP> concentration ([Ca<SUP>2&#8290;</SUP>]<I><SUB>i</SUB></I>) about 1.7 times the basal level of 72&#8273;5 nM, and 5,5 -dimethyl BAPTA/AM kept it constant at the basal level. This correlation between insulin-induced increases in 2-DG uptake and [Ca<SUP>2&#8290;</SUP>]<I><SUB>i</SUB></I> indicates that the elevation of [Ca<SUP>2&#8290;</SUP>]<I><SUB>i</SUB></I> may be prerequisite for the stimulation of glucose transport. Studies with inhibitors (ML-9, KN-62, cyclosporin A) of Ca<SUP>2&#8290;</SUP>-calmodulin dependent protein kinases/phosphatases also indicate an involvement of intracellular Ca<SUP>2&#8290;</SUP>. Additional studies with okadaic acid and calyculin A, protein phosphatase-1 (PP-1) and 2A (PP-2A) inhibitors, indicate an involvement of PP-1 in insulin action on 2-DG uptake. These results indicate an involvement of Ca<SUP>2&#8290;</SUP>-dependent signaling pathway in insulin action on glucose transport.