PANCREATIC BETA-CELL REGENERATION AFTER 48-H GLUCOSE-INFUSION IN MILDLY DIABETIC RATS IS NOT CORRELATED WITH FUNCTIONAL IMPROVEMENT

We investigated the effect of glucose infusion on beta-cell regenerati on in rats made mildly diabetic by a single injection of low dosage (3 5 mg/kg) streptozotocin (STZ). Nondiabetic (MD) and STZ rats were subm itted to a 48-h glucose infusion (hyperglycemia similar to 22 mmol/l i n both groups: ND and STZ hyperglycemic-hyperinsulinemic [ND HG-HI and STZ HG-HZ rats]). Before infusion, p-cen mass was 65% lower in STZ ra ts than in ND rats (2.0 +/-0.02 vs. 5.5 +/- .0.6 mg), 1.6-fold increas ed in ND HG-HI rats (8.7 +/- 1.7 mg), and 2.7-fold increased in STZ HG -HI rats (5.4 +/- 0.9 mg). In ND HG-HI rats, beta-cell enlargement was related to an increase in beta-cell responsiveness to nutrient secret agogues both in vivo and in vitro, whereas in STZ HG-HI rats, no signi ficant improvement in insulin secretion could be noticed. To determine the respective role of hyperglycemia and hyperinsulinemia on beta-cel l area changes, ND and STZ rats were submitted to a 48-h hyperinsuline mic-euglycemic clamp. No modification of beta-cell mass was detected i n either group. In conclusion, 48-h superimposed hyperglycemia was eno ugh to restore beta-cell mass previously reduced by STZ injection. Thi s effect seemed to be due to hyperglycemia rather than hyperinsulinemi a alone. The data stress the dissociation between beta-cell regenerati on and improvement in islet function in diabetic rats. Our model seems suitable for studying factors that can improve the plasticity and fun ction of the pancreas in NIDDM.