title: Impairment of the mitochondrial oxidative response to D-glucose in pancreatic islets from adult rats injected with streptozotocin during the neonatal period.
abstract: Pancreatic islets removed from adult rats injected with streptozotocin during the neonatal period display an impaired secretory response to D-glucose and, to a lesser extent, to L-leucine. Despite normal to elevated hexokinase and glucokinase activities in the islets of these glucose-intolerant animals and despite normal mitochondrial binding of the hexokinase isoenzymes, the metabolic response to a high concentration of D-glucose is severely affected, especially in terms of D-[6-14C]glucose oxidation. Thus, the ratio in D-[6-14C]glucose oxidation/D-[5-3H]glucose utilization is much less markedly increased in response to a rise in hexose concentration and, at a high concentration of D-glucose (16.7 mmol/l), less markedly decreased by the absence of Ca2+ and presence of cycloheximide in diabetic than control rats. This metabolic defect contrasts with (1) a close-to-normal or even increased capacity of the islets of diabetic rats to oxidize D-[6-14C]glucose, [2-14C]pyruvate, L-[U-14C]glutamine and L-[U-14C]leucine at low, non-insulinotropic, concentrations of these substrates; (2) a lesser impairment of the oxidation of L-[U-14C]leucine tested in high concentration (20 mmol/l), the effect of Ca2+ deprivation upon the latter variable being comparable in diabetic and control rats; (3) an unaltered transamination of either [2-14C]pyruvate or L-[U-14C]leucine; and (4) a modest perturbation of glycolysis. The most obvious alteration in glycolysis consists in a lesser increase of the glycolytic flux in response to a rise of D-glucose concentration in diabetic than control rats, this coinciding with an apparent decrease in affinity of glucokinase for the hexose.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Laboratoire de Physiologie du Développement, Université de Paris, France.
authors: M H
authors: MH
authors: Giroix
authors: A
authors: A
authors: Sener
authors: D
authors: D
authors: Bailbe
authors: B
authors: B
authors: Portha
authors: W J
authors: WJ
authors: Malaisse
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006593:Hexokinase / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007527:Isoenzymes / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013311:Streptozocin
chemical_list: D007527:Isoenzymes; D011773:Pyruvates; D013311:Streptozocin; D003513:Cycloheximide; D006593:Hexokinase; D007930:Leucine; D005947:Glucose; D002118:Calcium