Glucose-induced desensitization of the pancreatic beta-cell is species dependent

The capacity of 20 mM glucose to desensitize insulin release was determined . A prior exposure to 20 mM glucose impaired the response of rat islets to subsequent restimulation. Compared with control islets, insulin secretory r ates measured 25-30 min after the onset of 20 mM, glucose stimulation were reduced by 75%. Restimulation of glucose-desensitized islets with 20 mM glu cose plus 500 nM forskolin resulted in a dramatic enhancement of both phase s of secretion. In contrast to the desensitization of rat islets induced by prior 20 mM glucose exposure, mouse islets were immune to this adverse eff ect of the hexose. Prior exposure to 20 mM glucose had no adverse effect on glucose usage rates. The activation of phospholipase C in glucose-desensit ized rat islets was compromised when compared with control islets. The impa irment could not be accounted for by a decrease in immunoreactive content o f several major phospholipase C isozymes (beta 1 or delta 1) or their parti tioning between the membrane and cytosolic compartments. in contrast to rat islets, prior exposure of mouse islets to 20 mM glucose for 180 min had no effect on inositol phosphate accumulation. These observations document an additional difference between rat and mouse islets and suggest that the evo lution of desensitization is a consequence of the impaired activation of ph ospholipase C in rat islets.