EFFECT OF SULFONYLUREA AGENTS ON PYRUVATE-DEHYDROGENASE ACTIVITY IN CIRCULATING LYMPHOCYTES FROM PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM)

In circulating lymphocytes from patients with non-insulin-dependent di abetes mellitus (NIDDM) subnormal pyruvate dehydrogenase (PDH) activit y returns to normal following patient treatment with sulfonylurea (gli clazide, 80 mg twice daily/5 weeks). Moreover, in vitro in cells from diabetic patients exposed to insulin at 50 mu U/mL PDH activation als o occurs; in cells of controls the same happens for insulin at 5 mu U/ mL, whereas at 50 mu U/mL inhibition takes place. Therefore, the low P DH activity in cells of NIDDM patients might be caused by defective in sulin control on the enzyme and its recovery in gliclazide-treated pat ients by drug-mediated removal of the defect. The validity of the hypo thesis was verified in this study where cells of NIDDM patients before and after gliclazide treatment were exposed, in vitro, to insulin at 5 and 50 mu U/mL and then tested for PDH activity. In such conditions, the profile of PDH behavior in treated patients was no longer compara ble to that in untreated patients but closer to that in euglycemic con trols, thus supporting the view that the recovery of PDH activity in N IDDM patients following gliclazide treatment might be the expression o f an additional effect that the drug would have in these patients, aim ed to renew cell responsiveness to insulin.