Impaired Growth Hormone Response to Insulin‐induced Hypoglycaemia in Obese Patients: Restoration Blocked by Ritanserin After Fenfluramine Administration

Abstract

The aim of the present study was to test whether the serotoninergic system may be involved in the well known reduced growth hormone (GH) response to insulin-induced hypoglycaemia (IIH) in obese patients. Ten obese women and 10 normal-weight control women underwent three IIH tests, at 14-day intervals: the first in basal conditions, the other two after randomized administration of a serotoninergic drug, fenfluramine (FF, 120 mg/day for 7 days) and FF plus ritanserin (RIT, 30 mg/day for the first 2 days and 20 mg/day on the following days). Ritanserin is a new selective 5-HT2 blocker receptor agent. Both controls and obese patients showed similar normal basal GH levels before each test and insulin administration always effectively reduced glucose levels to values lower than 2-2 mmol/l. In the controls, the expected GH increase to IIH (peak value 56 f 13.4 mU/1, AUC 234.4 f 55 mU/min/ml) was unaffected by FF administration (peak value 43 f 11.4;AUC 216.8 f 34.8). In response to the first IIH, the obese patients showed a significantly lower GH increase than in the case of the controls (peak valut 2 1 -4 f 4.6 mU/1, P < 0.02; AUC 93.2 f 18.6, P < 0.02). However, in comparison with the basal test, FF administration significantly ( P < 0.00 1) enhanced GH response to insulin hypoglycaemia (peak value 33.4 f 4; AUC 150 f 14.6), reaching values not significantly different from those of the controls. This effect was completely antagonized by RIT administration (peak value 18 f 5; AUC 85.6 f 2 1). In conclusion, the reduced GH response to insulin hypoglycaemia in obese women has been confirmed in the present study. However, the restoration of the hormonal response obtained after FF administration in obese patients only, which is effectively antagonized by RIT, strongly suggests the involvement of the serotoninergic system in this impaired

Binding Protein for Human Growth Hormone: Effects of Age and Weight

“…Both spontaneous as well as stimulated GH secretion is reduced in obese children [31,32] and augmented dur ing starvation [33], while inverse changes are seen in serum IGF-I [34,35], At the cellular level, GH acutely down-regulates GH receptors in liver [36], whereas chronic administration augments hepatic GH binding [37] . The influence of nutrition on serum GHBP is likely to involve other hormonal mediators.…”

The role of leptin in regulating bone metabolism

“…Blunt growth hormone response is seen in obese individuals in response to insulin induced hypoglycemia as compared to healthy people [33]. In normal healthy men, after a 72-hour fasting, a rise in serum growth hormone (GH) levels, pulsatile frequency of GH and 24-hour integrated GH concentrations, but a decrease in IGF1, were noted, which was not reversed with leptin recombinant therapy [5].…”

A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction

“…The secretion of growth hormone in response to stimulation is generally decreased in obese children 19 , and the effects of growthhormone deficiency are mimicked, except that obese children have normal or slightly increased insulin-like growth factor-I (IGF-I) levels 20 and, often, accelerated growth 21 . The affected sisters here showed a mild but significant growth delay during early childhood (Figs 1 and 3), despite normal parental height.…”