Species differences in the induction of time-dependent potentiation of insulin secretion.

The secretory responsiveness of the pancreatic beta-cell can be markedly improved by prior short term exposure to a stimulatory glucose level. Termed time-dependent potentiation (TDP), priming, or sensitization, this phenomenon has been documented to occur in both human and rat islets and my involve, at least in part, information flow in the phospholipase C and protein kinase C (PKC) signal transduction pathway. In contrast to human and rat islets, however, mouse islets fail to exhibit TDP in response to priming with high glucose. In the present series of studies, we explored in more detail the conditions and stimulants necessary for the induction of TDP in mouse islets and compared these responses with those obtained in rat islets. In agreement with previous reports, high (15 mM) glucose alone primed the rat beta-cell, but not the mouse beta-cell, to subsequent restimulation with 15 mM glucose. However, muscarinic stimulation of mouse islets with carbachol (100 microM) in the presence of 15 mM glucose primed the beta-cell to a subsequent 15-mM glucose stimulus. In addition, prior exposure to 50 nM of the PKC activator tetradecanoyl phorbol acetate dramatically amplified the subsequent insulin secretory responses of mouse islets to 15 mM glucose. In contrast to its significant inhibitory effect on glucose-induced insulin release from rat islets, the PKC inhibitor staurosporine (50 nM) had not effect on 15 mM glucose-induced release from control or prior glucose-exposed mouse islets. However, staurosporine significantly reduced the priming effect of tetradecanoyl phorbol acetate or carbachol on 15 mM glucose-induced insulin secretion from mouse islets. These findings emphasize the dramatic species differences that exist in the capacity of prior high glucose stimulation to induce TDP in rat and, presumably, human islets, on the one hand, and mouse islets, on the other. They also serve to emphasize the role of phosphoinositide hydrolysis and PKC activation in the induction of TDP.