Effect of insulin on LHRH release by perifused hypothalamic fragments.

Insulin-deficient states are associated with an impaired function of the hypothalamic-pituitary-gonadal axis, but the mechanisms underlying hypothalamic alterations in experimental diabetes are still unknown. We investigated the effect of glucose concentrations, in the presence and absence of insulin, on LHRH release from perifused hypothalamic fragments from female adult ovariectomized rats. Glucose and insulin were added to the perifusion medium (Earle's, pH 7.4, gassed with 95% O2/5% CO2, flow rate 50 microliters/min). When glucose was absent (in the presence of insulin 10 mU/l), LHRH release was reduced, peak levels being < 5 pg/100 microliters. The addition of glucose (100 and 300 mg/dl), in the absence of insulin, resulted in peak LHRH levels fluctuating around 35 pg/100 microliters (p < 0.05 vs. glucose 0 mg/dl). When glucose (100 or 300 mg/dl) and insulin (10 mU/l) were combined, an eightfold increase in peak LHRH values was observed, and peak levels reached 300 pg/100 microliters (p < 0.05 vs. glucose 100 and 300 mg/dl alone). In conclusion, LHRH release by perifused hypothalamic fragments is dramatically increased by low concentrations of insulin; this occurs only when glucose is available. Acutely elevated glucose levels (from 100 to 300 mg/dl) do not affect LHRH release.

Diet only or diet and sulfonylureas in mild type II diabetes (NIDDM)? Pathophysiologic and therapeutic implications.

UNLABELLED: Plasma glucose, insulin and C-peptide responses to a test meal were studied in 7 nonobese patients with type II diabetes mellitus (NIDDM) treated with diet alone and after 6 months of gliclazide therapy, as well as in 6 matched controls. The glycemic levels were significantly higher (p less than 0.05) in patients under diet alone than in controls and after gliclazide treatment (peak: 12.8 +/- 1.0; 7.9 +/- 0.4 and 10.0 +/- 0.5 mmol/l, respectively; means +/- SEM). Diet and gliclazide treated patients showed a reduced B-cell response during the first hour after the meal as indicated by insulin and C-peptide values and areas (insulin areas 0-60 min: controls 57.9 +/- 10.9; p less than 0.01 vs diet alone 14.2 +/- 2.7 and vs gliclazide 22.1 +/- 2.8 microU/ml/min). The hypoinsulinemic phase lasted from 20 to 60 min before gliclazide, and from 20 to 45 min after gliclazide. The first significant C-peptide increase, detected at 10 min in controls and at 30 min under diet alone, was advanced to 15 min after gliclazide treatment. IN CONCLUSION: patients with mild, diet-treated NIDDM show a sluggish and attenuated B-cell response to a physiologic challenge (test meal); this secretory impairment is present even after a complete post-prandial glycemic normalization, supporting the idea of a persistent defect. Nevertheless, the slight improvement observed in insulin secretion after gliclazide treatment may be promoting, at least partially, the normalization of prandial hyperglycemia. The benefits of this normalization in diabetic patients previously controlled by diet only await further investigation.