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. 1974 Jan;138(1):33–45. doi: 10.1042/bj1380033

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

Bo Hellman 1, Lars-Åke Idahl 1, Åke Lernmark 1, Janove Sehlin 1, Inge-Bert Täljedal 1
PMCID: PMC1166172  PMID: 4601168

Abstract

The transport and oxidation of glucose, the content of fructose 1,6-diphosphate, and the release of insulin were studied in microdissected pancreatic islets of ob/ob 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 Ca2+, or the substitution of choline ions for Na+, or the addition of diazoxide had little if any effect on glucose transport. However, Ca2+ or Na+ 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-N-(3-hydroxyphenyl)-p-toluidinomethyl-2-imidazoline] counteracted the effects of adrenaline and Ca2+ deficiency on islet fructose 1,6-diphosphate. After equilibration in Na+-deficient medium, the islets exhibited an increase in basal insulin release whereas the secretory response to glucose was inhibited. The inhibitory effects of Na+ deficiency on the secretory responses to different concentrations of glucose correlated with those on 14CO2 production. When islets were incubated with 17mm-glucose, the sudden replacement of Na+ 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-O-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 Ca2+ or Na+ 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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