Abstract
We studied the effect of a specific-competitive inhibitor of the sucrose taste response, p-nitrophenyl-D-glucopyranoside (PNP-Glu) on insulin release and phosphoinositide metabolism in rat pancreatic islets. The α-anomer, but not the β-anomer, of PNP-Glu at a concentration of 5mM inhibited insulin release induced by 10mM glucose. Islets were labeled by exposure for 2h to 10 uCi of myo-[2-3H] inositol solution supplemented with 2.8mM glucose. Forty islets were then incubated in the presence of 10mM LiCl, 1mM inositol and 10mM glucose with or without the anomers of PNP-Glu.[3H] radioactivity in the incubation medium remained significantly greater in the presence of the α-anomer of PNP-Glu than in the presence of glucose alone after 5-and 20-min incubation. The inositol monophosphate levels in the islets incubated with glucose alone were increased more than in the islets with α-anomer. The β-anomer of PNP-Glu did not change either glucose-induced insulin release or phosphoinositide breakdown. A patch-clamp study revealed that neither anomer affected the glucose-dependent ATP-sensitive K+-channels. These results indicate that the anomeric preference for glucose in insulin release in the pancreatic islets is closely associated with phosphoinositide breakdown.
