Beta cell adaptation to dexamethasone-induced insulin resistance in rats involves increased glucose responsiveness but not glucose effectiveness

Islet beta cell adaptation to dexamethasone-induced insulin resistance was characterized with respect to glucose-stimulated insulin secretion and isle t innervation. Male Sprague-Dawley rats were injected daily with dexamethas one (2 mg/kg for 12 days), which resulted in hyperinsulinemia and hyperglyc emia compared with controls (which were injected with sodium chloride). Ins ulin secretion was characterized in collagenase-isolated islets. Islet inne rvation was examined by immunocytochemical analysis of tyrosine hydroxylase , neuropeptide Y (sympathetic nerves), and vasoactive intestinal poly pepti de (cholinergic nerves). In islets isolated from the insulin-resistant anim als, the insulin response to 3.3 or 8.3 mM glucose was three times greater during perifusion compared with controls (p < 0.001). Incubation of islets at 0 to 20 mM glucose revealed a marked leftward shift of the glucose dose- response relation after dexamethasone treatment (potency ratio, 1.78; p < 0 .01), with no difference at 0 or 20 mM glucose. Thus, the potency but not t he efficacy of glucose was increased. The number of islet nerves did not di ffer between dexamethasone-treated rats and controls. Dexamethasone-induced insulin resistance leads to adaptively increased glucose responsiveness of the islet beta cells, with increased potency, but not increased efficacy, of glucose to stimulate insulin secretion without any evidence of altered i slet innervation.