Studies on the role of β-cell metabolism in the insulinotropic effect of α-ketoisocaproic acid |
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Authors: | Susanne Holze Uwe Panten |
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Institution: | Institute for Pharmacology and Toxicology, University of Göttingen, Robert-Koch-Str. 40, D-3400 Göttingen, F.R.G. |
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Abstract: | α-Ketoisocaproic acid has been shown to be apotent insulin secretagogue but the mechanism has not been elucidated. To define the role of β-cell metabolism in the insulinotropic activity of α-ketoisocaproic acid the utilization of glucose and the oxidation of α-ketoisocaproic and isovaleric acid by incubated islets of obese hyperglycemic mice were measured.Glucose metabolism was never enhanced by α-ketoisocaproic acid. The same 14CO2 amounts were released from the non-secretagogue 1-14C]isovaleric acid (10 mM) or from α-keto 2-14C]isocaproic acid (5–20 mM). Pyruvate (20 mM) did not inhibit α-ketoisocaproic acid-induced insulin secretion in spite of reduction of decarboxylation of α-ketoisocaproic acid by more than 40%.The results indicate that stimulated insulin release in response to α-ketoisocaproic acid is not mediated by an indirect increase in glucose metabolism and further suggest that isovaleryl-CoA and following CoA-esters in α-ketoisocaproic acid degradation are not likely recognized as signals. The possibility, however, remains that enhanced intramitochondrial production of reducing equivalents elicits insulin secretion. |
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Keywords: | Insulin secretion Glucose metabolism α-ketoisocaproic acid Isovaleric acid |
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