Resistance to Insulin-Stimulated Glucose Uptake in Adipocytes Isolated From Spontaneously Hypertensive Rats

The ability of insulin to stimulate glucose uptake and inhibit catecholamine-induced lipolysis was measured in adipocytes of similar size isolated from SHR and WKY rats. The results indicate that glucose transport was decreased in adipocytes from SHR rats; both basal (19 ± 2 vs. 32 ± 2 fmol · cell−1 · s−1 P < .001) and maximal (207 ± 30 vs. 373 ± 20 fmol · cell−1 · s−1 P < .01) insulin-stimulated glucose transport were lower in SHR than in WKY rats. In addition, the EC50 of insulin-stimulated glucose uptake was higher (921 ± 82 vs. 557 ± 69 pM insulin, P < .05) in adipocytes from SHR rats than from WKY rats. The ability of phenylisopropyladenosine (PIA) to modulate basal and maximal insulin-stimulated glucose uptake was compared in adipocytes from SHR and WKY rats. These results also demonstrated that glucose uptake was decreased in adipocytes from SHR rats and that PIA similarly enhanced both basal and maximal insulin-stimulated glucose uptake in adipocytes from both groups. Although maximal isoproterenol-stimulated lipolysis was decreased in adipocytes from SHR rats, the ability of insulin to inhibit catecholamine-stimulated lipolysis was at least as great in adipocytes from SHR as from WKY rats. Despite the decrease in insulin-stimulated glucose transport in isolated adipocytes from SHR rats, total number of insulin receptors, their affinity for insulin, and the ability of insulin to stimulate receptor-associated tyrosine kinase activity were similar in adipocytes from SHR and WKY rats. These results demonstrate a defect in both basal and insulin-stimulated glucose uptake and a loss of sensitivity of the adipocyte glucose-transport system to insulin in adipocytes from SHR rats and suggest that the site of the abnormality is distal to the insulin receptor.

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