Streptozotocin-induced FAD-glycerophosphate dehydrogenase suppression in pancreatic islets

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Abstract
In vitro, streptozotocin (1.0–2.0 mM) fails to exert any immediate effect on the activity of FAD-glycerophosphate dehydrogenase in either pancreatic islet homogenate or freshly isolated intact islets. However, when injected in vivo, streptozotocin (40 mg/kg body weight) lowers the specific activity of the FAD-linked enzyme in islet homogenates within 24 h, whilst causing little change in 2-ketoglutarate dehydrogenase and increasing glutamate dehydrogenase islet activity. In animals which became frankly hyperglycaemic as the result of the injection of streptozotocin, the activity of islet FAD-glycerophosphate dehydrogenase, measured 2 weeks after administration of the B-cell cytotoxic agent, was decreased to 10–20% of its control value. Neither insulin treatment nor riboflavin supplementation affected this enzymic defect. Even when the animals injected with streptozotocin remained virtually euglycaemic, the activity of islet FAD-glycerophosphate dehydrogenase was markedly decreased. This coincided with a preferential impairment of aerobic glycolysis, as judged from the ratio betweend-[3,4-14C]glucose oxidation andd-[5-3H] glucose utilization by the islets. It is proposed, therefore, that the administration of sub-diabetogenic amounts of streptozotocin to adult rats represents an alternative and easier approach to the study of B-cell dysfunction in this model of type 2 (non-insulin-dependent) diabetes than does streptozotocin injection in neonatal rats.