title: Stimulation of proinsulin biosynthesis and insulin release by pyruvate and lactate.
abstract: 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.
mesh_terms: 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
chemical_list: D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D000496:Alloxan; D011384:Proinsulin; D005947:Glucose