Streptozotocin-induced FAD-glycerophosphate dehydrogenase suppression in pancreatic islets. Relationship with the severity and duration of hyperglycaemia and resistance to insulin or riboflavin treatment.
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 between D-[3,4-14C]glucose oxidation and D-[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.
Rasschaert
J
J
Laboratory of Experimental Medicine, Brussels Free University, Erasme School of Medicine, Belgium.
Malaisse
W J
WJ
D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D012256:Riboflavin / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D005182:Flavin-Adenine Dinucleotide; D000496:Alloxan; D005993:Glycerolphosphate Dehydrogenase; D007655:Ketoglutarate Dehydrogenase Complex; D005969:Glutamate Dehydrogenase; D005947:Glucose; D012256:Riboflavin