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Glucose both inhibits and stimulates insulin secretion from isolated pancreatic islets exposed to maximally effective concentrations of sulfonylureas

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Summary

Isolated pancreatic islets from mice were perifused with media containing maximally effective concentrations of glibenclamide (0.1–10 μmol/l) or glipizide (1 μmol/l). In these islets an increase of the glucose concentration from 10 mmol/l to 40 mmol/l or addition of d-glyc-eraldehyde (20 mmol/1) caused a temporary decrease in insulin release which was followed by a sustained enhancement of release. α-Ketoisocaproate (3 or 20 mmol/1) did not inhibit insulin release; at high concentration it was an even stronger secretagogue than d-glucose or d-glyceraldehyde. It is concluded that high energy phosphates couple B-cell fuel metabolism and insulin release by acting both on the ATP-dependent K+ channel and on other targets not yet identified.

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Some of the results described here are part of the medical thesis of A. Wallasch

Send offprint requests to U. Panten at the above address

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Panten, U., Schwanstecher, M., Wallasch, A. et al. Glucose both inhibits and stimulates insulin secretion from isolated pancreatic islets exposed to maximally effective concentrations of sulfonylureas. Naunyn-Schmiedeberg's Arch Pharmacol 338, 459–462 (1988). https://doi.org/10.1007/BF00172128

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  • DOI: https://doi.org/10.1007/BF00172128

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