Nutrient-induced priming of insulin and glucagon secretion. Effects of alpha-ketoisocaproic acid.
Previous exposure to glucose enhances the insulin and depresses the glucagon response to subsequent stimulation with different secretagogues. Induction of these priming effects of glucose requires the metabolism of the sugar. To investigate whether induction of the priming effect of glucose is coupled to glycolysis, other nutrients were tested for their ability to mimic the glucose effect. In isolated perfused rat pancreas prior exposure for 30 min to 10 mM D-glyceraldehyde or 10 mM alpha-ketoisocaproic acid (KIC) enhanced the insulin response to subsequent stimulation with 3-isobutyl-methylxanthine (P less than 0.01); 20 mM pyruvate, 10 mM octanate, 20 mM succinate, or 20 mM citrate were ineffective. The priming effect of KIC was also investigated in relation to subsequent stimulation with a second, identical pulse of KIC. Five millimolar KIC evoked a marked first phase insulin release, followed by a small and constant second phase insulin release. When KIC was reintroduced, the first phase was enhanced (by 100%), and the peak response appeared 1 min earlier; whereas second phase insulin release was unaffected. A priming effect of KIC on arginine-induced glucagon secretion was tested after perfusion for 20 min with 10 mM KIC before the introduction of 8 mM L-arginine. Previous exposure to KIC did not significantly inhibit glucagon secretion, whereas the concomitant insulin release was augmented.


CONCLUSIONS
the ability of nutrient secretagogues to induce priming of insulin secretion does not depend on the glycolytic pathway but may correlate with the degree of oxidative metabolism of these substrates.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002208:Caproates / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002208:Caproates; D007328:Insulin; D007651:Keto Acids; C013082:alpha-ketoisocaproic acid; D005934:Glucagon; D001120:Arginine; D015056:1-Methyl-3-isobutylxanthine