ENZYMATIC, METABOLIC AND SECRETORY PATTERNS IN HUMAN ISLETS OF TYPE-2(NON-INSULIN-DEPENDENT) DIABETIC-PATIENTS

Islets were isolated by automatic digestion from non-diabetic cadaveri c organ donors and from Type 2 (non-insulin-dependent) diabetic subjec ts. The activity of FAD-glycerophosphate dehydrogenase, but not that o f either glutamate dehydrogenase, glutamate-oxalacetate transaminase o r glutamate-pyruvate transaminase, was lower in Type 2 diabetic patien ts than control subjects. Hexokinase, glucokinase and glutamate decarb oxylase activities were also measured in islets from control subjects. The utilization of D-[5-H-3]glucose, oxidation of D-[6-C-14]glucose a nd release of insulin evoked by D-glucose were all lower in Type 2 dia betic patients than control subjects. The secretory response to the co mbination of L-leucine and L-glutammine appeared less severely affecte d. Islets from Type 2 diabetic patients may thus display enzymatic, me tabolic and secretory anomalies similar to those often observed in ani mal models of Type 2 diabetes, including a deficiency of beta-cell FAD -linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle.