Glucose-induced release of insulin from perifused rat islets is associated with elevated islet adenosine 3',5'-monophosphate. If values for adenosine 3',5'-monophosphate are compared to insulin release during theophylline or glucose stimulation and theophylline plus glucose stimulation, it suggests a minor role for adenosine 3',5'-monophosphate in directly stimulating insulin release but a prominent role in modulating glucose-induced release of insulin.

No abstract

Although large quantities of zinc have been measured in pancreatic islets and correlated with islet B-cell function, potential artifacts in histochemical techniques and the existence of zinc-free insulin in certain species leave its role in insulin storage and secretion unclear. In this investigation, we examined the kinetics of uptake of 6s zinc into isolated rat islets and the distribution of both 6s zinc and endogenous islet zinc in islet subfractions. In addition, the chemically formed 65 zinc-sodium insulin kinetics of complexes were studied.Net uptake of 6S zinc was slow, being almost linear for the first 4 h and not reaching isotopic equilibrium over the 24 h of culture. Culture of islets in high glucose (25.6 mM) resulted in a diminished net 65 zinc uptake and significantly decreased content of both endogenous zinc and insulin when compared with culture in low glucose (5.6 mM). Analysis of "zinc and endogenous zinc distribution in islet subfractions revealed a low percentage of 65 zinc and endogenous zinc in the granule-enriched fractions: about 90% of total "zinc and 80% of endogenous zinc were associated with nongranular fractions. A comparison of the specific activity of the granular fractions with the lighter sucrose fractions revealed a nonequilibration of the "zinc taken up with the granular zinc pool. Chemical analysis of "zinc-insulin complexes revealed an almost instantaneous binding of "zinc to zinc-free insulin. Dissociation of preformed "zincinsulin complexes was slow, but some dissociation occurred with a lowering of the pH.We demonstrated that net zinc uptake by cultured islets is a slow phenomenon reduced by a high glucose environment. Although chemical analyses suggest a strong affinity of "zinc for insulin, only small quantities of "zinc, as well as endogenous zinc, associated with the granule-enriched fractions, and equilibration of granular "zinc with islet "zinc pools did not occur over 24 h. Thus, zinc may be needed in other metabolic processes besides insulin crystallization in the B cell. DIABETES 29:767-773, October 1980.