Abstract
α-Ketoisocaproic acid released insulin from isolated mouse islets with a threshold concentration at 2-3 mM and a maximal effect at 15-20 mM. Stimulation of insulin secretion was accompanied by small increases of cyclic AMP accumulation by islets which could be prevented by omission of Ca2+ from the incubation media. Extramitochondrial metabolites that could arise from α-ketoisocaproic acid released much less insulin than their mother substance. Accumulation of intramitochondrial CoA compounds typical for degradation of α-ketoisocaproic acid probably did not cause the specific B-cell response to this keto acid. It is concluded that metabolites do not represent primary signals during α-ketoisocaproic acid-induced insulin secretion. The experimental data are compatible with the view that increase of intramitochondrial production of reducing equivalents is necessary for recognizing insulin-releasing fuels by B-cells.
ACKNOWLEDGMENTS We thank Professor E. Brunner and his colleagues for help with the statistical testing.
- Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics
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