Stimulation of insulin release from pancreatic islets by quinones.
Coenzyme Q (CoQ0) and other quinones were shown to be potent insulin secretagogues in the isolated pancreatic islet. The order of potency was CoQ0 congruent to benzoquinone congruent to hydroquinone-menadione. CoQ6 and CoQ10 (ubiquinone), duroquinone and durohydroquinone did not stimulate insulin release. CoQ0's insulinotropism was enhanced in calcium-free medium and CoQ0 appeared to stimulate only the second phase of insulin release. CoQ0 inhibited inositol mono-, bis- and trisphosphate formation. Inhibitors of mitochondrial respiration (rotenone, antimycin A, FCCP and cyanide) and the calcium channel blocker verapamil, did not inhibit CoQ0-induced insulin release. Dicumarol, an inhibitor of quinone reductase, did not inhibit CoQ0-induced insulin release, but it did inhibit glucose-induced insulin release suggesting that the enzyme and quinones play a role in glucose-induced insulin release. Quinones may stimulate insulin release by mimicking physiologically-occurring quinones, such as CoQ10, by acting on the plasma membrane or in the cytosol. Exogenous quinones may bypass the quinone reductase reaction, as well as many reactions important for exocytosis.
MacDonald
M J
MJ
Childrens Diabetes Center, University of Wisconsin Medical School, Madison 53706.
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D001728:Dicumarol / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D011809:Quinones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014451:Ubiquinone / Q000494:pharmacology
D016227:Benzoquinones; D007295:Inositol Phosphates; D007328:Insulin; D011809:Quinones; D014451:Ubiquinone; C004532:quinone; D001728:Dicumarol; D005947:Glucose; D002118:Calcium