INCREASED GLUCOCORTICOID SENSITIVITY IN ISLET BETA-CELLS - EFFECTS ONGLUCOSE 6-PHOSPHATASE, GLUCOSE CYCLING AND INSULIN RELEASE

Glucose-6-phosphatase (G6Pase) activity and the rate of glucose cyclin g are increased in islets from animal models of TypeII (non-insulin-de pendent) diabetes mellitus. Glucocorticoid treatment further stimulate s these processes and inhibits glucose-induced insulin release. To det ermine whether these effects result from a direct action of glucocorti coids on the beta-cells, we used isolated islets. The islets were from transgenic mice overexpressing the glucocorticoid receptor in their b eta-cells to increase the cells' sensitivity to glucocorticoid. Islets from transgenic and non-transgenic control mice utilized and oxidized the same amount of glucose. In contrast, islet G6Pase activity was 70 % higher, glucose cycling was increased threefold and insulin release was 30% lower in islets from transgenic mice. Hepatic G6Pase activity was the same in transgenic and control mice. Dexamethasone administrat ion increased G6Pase activity and glucose cycling and decreased insuli n release in both transgenic and control mouse islets. We conclude tha t glucocorticoids stimulate islet G6Pase activity and glucose cycling by acting directly on the beta-cell. That activity may be linked to th e inhibition of insulin release.