Stimulation of proinsulin biosynthesis and insulin release by pyruvate and lactate.
Increasing concentrations of pyruvate failed to stimulate proinsulin biosynthesis and insulin release in freshly isolated islets. Glycolytic flux (3H2O from [5-3H]glucose) decreased by 80-85%, but decarboxylation of [1(-14)C]pyruvate was unaffected in islets tested immediately after alloxan exposure. This strongly suggested that in freshly isolated islets, beta-cells, in relation to other islet cells, hardly contribute to the decarboxylation of pyruvate. Non-alloxan-treated cultured islets decarboxylated 2-2.5 times as much pyruvate as did alloxan-treated islets cultured for 15-18h. Thus the contribution of beta-cells to the metabolism of pyruvate after culturing markedly increased. Concomitantly beta-cells became responsive to pyruvate. At 20mM-pyruvate, release of prelabelled proinsulin and insulin and incorporation of [3H]leucine into proinsulin reached values approximately half of those obtained with 20mM-glucose. Lactate was as effective as pyruvate in inducing responses in cultured islets. The experiments indicate that a critical degree of substrate utilization is necessary for the generation of signals for insulin release and proinsulin biosynthesis.
D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003653:Decarboxylation; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007773:Lactates / Q000494:pharmacology*; D008297:Male; D011384:Proinsulin / Q000096:biosynthesis*; D011773:Pyruvates / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects
D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D000496:Alloxan; D011384:Proinsulin; D005947:Glucose