Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin.
In islets from adult rats injected with streptozocin during the neonatal period, the oxidative and secretory responses to D-glucose are more severely affected than those evoked by L-leucine. A possible explanation for such a preferential defect was sought by comparing the rate of aerobic glycolysis, taken as the sum of D-[3,4-14C]glucose conversion to labeled CO2, pyruvate, and amino acid, with the total glycolytic flux, as judged from the conversion of D-[5-3H]glucose to 3H2O. A preferential impairment of aerobic relative to total glycolysis was found in islets from diabetic rats incubated at either low or high D-glucose concentration. This coincided in islet mitochondria of diabetic rats with a severe decrease in both the basal (no-Ca2+) generation of 3H2O from L-[2-3H]glycerol-3-phosphate and the Ca2(+)-induced increment in [3H]glycerophosphate detritiation. The mitochondria of diabetic rats were also less efficient than those of control animals in generating 14CO2 from [1-14C]-2-ketoglutarate. The diabetes-induced alteration of 2-ketoglutarate dehydrogenase in islet mitochondria was less marked, however, than that of the FAD-linked glycerophosphate dehydrogenase and was not associated with any change in responsiveness to Ca2+. Sonicated islet mitochondria of diabetic rats displayed normal to slightly elevated glutamate dehydrogenase activity. We propose, therefore, that the preferential impairment of the oxidative and secretory responses of islet cells to D-glucose in this experimental model of diabetes may be at least partly attributable to an altered transfer of reducing equivalents into the mitochondria as mediated by the glycerol phosphate shuttle.
Giroix
M H
MH
Laboratory of Developmental Physiology, University of Paris, France.
Rasschaert
J
J
Bailbe
D
D
Leclercq-Meyer
V
V
Sener
A
A
Portha
B
B
Malaisse
W J
WJ
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism* / Q000502:physiology; D006019:Glycolysis / Q000502:physiology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D013311:Streptozocin
D005994:Glycerophosphates; D013311:Streptozocin; D005969:Glutamate Dehydrogenase; D005947:Glucose; D002118:Calcium