The stimulus-secretion coupling in glucose-induced insulin release xliv. A possible link between glucose metabolism and phosphate flush.
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, alpha-ketoisocaproate and L-leucine, also provoked a phosphate flush. No flush occurred in islets exposed to non-insulinotropic nutrients (L-glutamine and and L-lactate) or non-nutriet 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 K4, and virtually abolished in the presence of menadione (10 mumol/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.
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007651:Keto Acids / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D009249:NADP / Q000096:biosynthesis; D010101:Oxygen Consumption; D010710:Phosphates / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects
D007328:Insulin; D007651:Keto Acids; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D009249:NADP; D000255:Adenosine Triphosphate; D007930:Leucine; D005947:Glucose