The stimulus-secretion coupling of glucose-induced insulin release

Abstract

Above a threshold of 3.0–4.2 mmol/l, D-glucose provoked a transient increase in ³²P fractional outflow rate from rat pancreatic islets prelabelled with ³²P-orthophosphate. Nutrients which stimulate insulin release in the absence of glucose, α-ketoisocaproate and L-leucine, also provoked a phosphate flush. No flush occurred in islets exposed to non-insulinotropic nutrients (L-glutamine and L-lactate) or non-nutrient secretagogues (arginine, tolbutamide, theophylline). A late increase in ³²P fractional outflow rate was observed in Ca²⁺ deprived islets stimulated with BaCl₂ and theophylline. The occurrence of a phosphate flush did not appear to be attributable to changes in insulin release, cyclic AMP content, membrane polarisation, K⁺ conductance, or reduced pyridine nucleotide content. The ³²P response to glucose was slightly decreased in the absence of extracellular Ca²⁺ or HCO₃ ^-, markedly impaired in the absence of K⁺, and virtually abolished in the presence of menadione (10 μmol/l). It is proposed that the occurrence of a phosphate flush is linked to the metabolism of nutrient secretagogues, possibly via an increase in O₂ uptake and the production rate of NAD(P)H and ATP.