Summary
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-14 C]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 [2-14 C]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. It is speculated that the preferential impairment of the metabolic and secretory response to D-glucose may be mainly attributable to an altered coupling between calcium accumulation and the stimulation of oxidative events in Beta-cell mitochondria of diabetic rats.
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Giroix M-H, Portha B, Kergoat M, Bailbe D, Picon L (1983) Glucose insensitivity and aminoacid hypersensitivity of insulin release in rats with non-insulin-dependent diabetes: a study with the perfused pancreas. Diabetes 32: 445–451
Portha B (1985) Decreased glucose-induced insulin release and biosynthesis by islets of rats with non-insulin-dependent diabetes: effect of tissue culture. Endocrinology 117: 1735–1741
Portha B, Giroix M-H, Serradas P, Welsh N, Hellerström C, Sener A, Malaisse WJ (1988) Insulin production and glucose metabolism in isolated pancreatic islets of rats with non-insulin-dependent diabetes. Diabetes 37: 1226–1233
Portha B, Levacher C, Picon L, Rosselin G (1974) Diabetogenic effect of streptozotocin in the rat during the perinatal period. Diabetes 23: 889–895
Portha B, Picon L, Rosselin G (1979) Chemical diabetes in the adult rat as the spontaneous evolution of neonatal diabetes. Diabetologia 17: 371–377
Bergmeyer HU, Bernt E (1974) D-glucose determination with glucose oxidase and peroxidase. In: Bergmeyer HU (ed) Methods of Enzymatic Analysis. Academic, New York, pp 1205–1215
Leclercq-Meyer V, Marchand J, Woussen-Colle MC, Giroix M-H, Malaisse WJ (1985) Multiple effects of leucine on glucagon, insulin, and somatostatin secretion from the perfused rat pancreas. Endocrinology 116: 1168–1174
Malaisse-Lagae F, Malaisse WJ (1984) Insulin release by pancreatic islets. In: Larner J, Pohl SL (eds) Methods in diabetes research. Wiley and Sons, New York, pp 147–152
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275
Carpinelli AR, Sener A, Herchuelz A, Malaisse WJ (1980) The stimulus-secretion coupling of glucose-induced insulin release. XLI. Effect of intracellular acidification upon calcium efflux from islet cells. Metabolism 29: 540–545
Malaisse WJ, Sener A (1988) Hexose metabolism in pancreatic islets. Feedback control of D-glucose oxidation by functional events. Biochim Biophys Acta 971: 246–254
Malaisse WJ, Sener A, Malaisse-Lagae F, Hutton JC, Christophe J (1981) The stimulus-secretion coupling of amino acid-induced insulin release. VI. Metabolic interaction of L-glutamine and 2-ketoisocaproate in pancreatic islets. Biochim Biophys Acta 677: 39–49
Sener A, Malaisse-Lagae F, Malaisse WJ (1987) Fructose metabolism via the pentose cycle in tumoral islet cells. Eur J Biochem 170: 447–452
Sener A, Malaisse-Lagae F, Giroix M-H, Malaisse WJ (1986) Hexose metabolism in pancreatic islets: compartmentation of hexokinase in islet cells. Arch Biochem Biophys 251: 61–67
Giroix M-H, Sener A, Pipeleers DG, Malaisse WJ (1984) Hexose metabolism in pancreatic islets. Inhibition of hexokinase. Biochem J 223: 447–453
Malaisse WJ, Sener A, Carpinelli AR, Anjaneyulu K, Lebrun P, Herchuelz A, Christophe J (1980) The stimulus-secretion coupling of glucose-induced insulin release. XLVI. Physiological role of L-glutamine as a fuel for pancreatic islets. Mol Cell Endocrinol 20: 171–189
Sener A, Malaisse-Lagae F, Dufrane SP, Malaisse WJ (1984) The coupling of metabolic to secretory events in pancreatic islets. The cytosolic redox state. Biochem J 220: 433–440
Malaisse WJ, Hutton JC, Carpinelli AR, Herchuelz A, Sener A (1980) The stimulus-secretion coupling of amino acid-induced insulin release. I. Metabolism and cationic effects of L-leucine. Diabetes 29: 431–437
Eizirik DL, Sandler S, Sener A, Malaisse WJ (1988) Defective catabolism of D-glucose and L-glutamine in mouse pancreatic islets maintained in culture after streptozotocin exposure. Endocrinology 123: 1001–1007
Sener A, Malaisse-Lagae F, Malaisse WJ (1983) Does leucine and norleucine-induced insulin release depend on amino acid aminotransferase activity? J Biol Chem 258: 6693–6694
Zähner D, Malaisse WJ (1989) Altered kinetic behaviour of liver glucokinase in streptozotocin-diabetic rats. Diabetes 38 [Suppl 2]: 104A (Abstract)
Sener A, Malaisse WJ (1987) Stimulation by D-glucose of mitochondrial oxidative events in islet cells. Biochem J 246: 89–95
Malaisse WJ, Rasschaert J, Sener A (1990) Activation of the 2-ketoglutarate dehydrogenase complex in glucose-stimulated pancreatic islets. Diabetes 39 [Suppl 1]: 66A
Malaisse WJ (1988) Insulin release: physiology and pathophysiology of nutrient metabolism in pancreatic islets. In: Grill V (ed) Pathogenesis of non-insulin dependent diabetes mellitus. Raven, New York, pp 27–38
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Giroix, M.H., Sener, A., Bailbe, D. et al. Impairment of the mitochondrial oxidative response to D-glucose in pancreatic islets from adult rats injected with streptozotocin during the neonatal period. Diabetologia 33, 654–660 (1990). https://doi.org/10.1007/BF00400566
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DOI: https://doi.org/10.1007/BF00400566