Effects of alpha-ketomonocarboxylic acids upon insulin secretion and metabolism of isolated pancreatic islets

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Abstract
Summary In perifused isolated pancreatic islets alpha-ketoisocaproic acid (KIC) or alpha-ketocaproic acid (KC) induced a high insulin secretion rate and a steep increase of the fluorescence of reduced pyridine nucleotides [NAD(P)H] which fell again to almost prestimulatory levels 6 min after medium change. Insulin release in response to alpha-ketooctanoic (KO) acid started slowly and was accompanied by a decrease of the NAD(P)H-fluorescence trace. Beta-phenylpyruvate which is known to initiate insulin release also caused a fluorescence decrease. Alpha-ketoisovaleric (KIV) acid or pyruvate had no significant effects upon insulin secretion or NAD(P)H-fluorescence. In contrast to L-leucine, L-norleucine or L-valine did not enhance insulin release or fluorescence of NAD(P)H. KIV, alpha-keto-beta-methylvaleric acid (KMV), KIC and KC raised the production of their corresponding amino acids by islet cells. From these results it is concluded that alpha-ketomonocarboxylic acids as such trigger insulin release by acting upon receptor sites which differ from those occupied by amino acids.