DIFFERENCES IN INSULIN-SECRETION BETWEEN THE RAT AND MOUSE - ROLE OF CAMP

Although information regarding insulin secretion usually Is considered equivalent when generated in the mouse or the rat, it is established that the kinetics of insulin secretion fi:om mouse and rat pancreatic beta cells differ. The mechanisms underlining these differences are no t understood. The in vitro perfused pancreas and isolated islets of th e mouse or rat were employed in this study to investigate the role of cyclic adenosine monophosphate (cAMP), a major positive modulator of b eta-cell function, as one differentiating signal for the uniquely diff erent insulin release from the beta cells of these commonly used roden ts. Glucose-stimulated first-phase insulin release from the perfused p ancreas of the rat was higher than the mouse when calculated per gram of pancreas or as fractional secretion, but this phase was identical i n the two species when results were adjusted for total body weight. Wh ether related to insulin content, pancreatic weight or body weight, th e rat pancreas responded to glucose with a progressively increasing se cond-phase insulin release compared to the mouse pancreas, which secre ted a flat second-phase of lesser magnitude. Isolated islets from rat and mouse were comparable in insulin content whereas the basal cAMP le vel of mouse islets was less than half that of the rat. At submaximal stimulation with glucose or glucose + IBMX or forskolin, mouse islets exhibited lower cAMP levels to a given stimulus than the rat. In rat i slets cAMP levels increased to approximately 1000 fmol per islet, alth ough insulin secretion maximized by 100-150 fmol. Insulin release at t he same 100-150 fmol cAMP per mouse islet was one-third that of the ra t and secretion had not maximized in mouse islets at 800 fmol. Despite their similar insulin contents, mouse islets consistently secreted le ss insulin for a given level of cAMP per islet than the rat. The lower capacity of mouse islets to achieve comparable cAMP levels was not th e result of increased catabolic rate because the ''half-time'' disappe arance of islet cAMP after a stimulus was similar (similar to 1 min) f or both species. It is concluded that, compared to the mouse, beta cel ls of the rat pancreas elicit a more pronounced second-phase insulin s ecretion that is due, at least in part, to a greater production of, an d sensitivity to, cAMP.