The pancreatic β-cell recognition of insulin secretagogues. Effects of calcium and sodium on glucose metabolism and insulin release

摘要

pThe transport and oxidation of glucose, the content of fructose 1,6-diphosphate, and the release of insulin were studied in microdissected pancreatic islets of iob/i/iob/i mice incubated in Krebs–Ringer bicarbonate medium. Under control conditions glucose oxidation and insulin release showed a similar dependence on glucose concentration with the steepest slope in the range 5–12mm. The omission of Casup2+/sup, or the substitution of choline ions for Nasup+/sup, or the addition of diazoxide had little if any effect on glucose transport. However, Casup2+/sup or Nasup+/sup deficiency as well as diazoxide (7-chloro-3-methyl-1,2,4-benzothiadiazine 1,1-dioxide) or ouabain partially inhibited glucose oxidation. These alterations of medium composition also increased the islet content of fructose 1,6-diphosphate, as did the addition of adrenaline. Phentolamine [2-iN/i-(3-hydroxyphenyl)-ip/i-toluidinomethyl-2-imidazoline] counteracted the effects of adrenaline and Casup2+/sup deficiency on islet fructose 1,6-diphosphate. After equilibration in Nasup+/sup-deficient medium, the islets exhibited an increase in basal insulin release whereas the secretory response to glucose was inhibited. The inhibitory effects of Nasup+/sup deficiency on the secretory responses to different concentrations of glucose correlated with those on sup14/supCOsub2/sub production. When islets were incubated with 17mm-glucose, the sudden replacement of Nasup+/sup by choline ions resulted in a marked but transient stimulation of insulin release that was not accompanied by a demonstrable increase of glucose oxidation. Galactose and 3-iO/i-methylglucose had no effect on glucose oxidation or on insulin release. The results are consistent with a metabolic model of the β-cell recognition of glucose as insulin secretagogue and with the assumption that Casup2+/sup or Nasup+/sup deficiency, or the addition of adrenaline or diazoxide, inhibit insulin release at some step distal to stimulus recognition. In addition the results suggest that these conditions create a partial metabolic block of glycolysis in the β-cells. Hence the interrelationship between the processes of stimulus recognition and insulin discharge may involve a positive feedback of secretion on glucose metabolism./p