IN OBESITY, GLUCOSE-LOAD LOSES ITS EARLY INHIBITORY, BUT MAINTAINS ITS LATE STIMULATORY, EFFECT ON SOMATOTROPE SECRETION

Glucose load has a biphasic effect on GH secretion. In fact, in normal subjects, glucose load has a prompt inhibitory and a late stimulatory effect on both spontaneous and GHRH-induced GH levels. The mechanism underlying the inhibitory effect is probably mediated by the increase in hypothalamic somatostatin, whereas that underlying the stimulatory effect is unclear. On the other hand, in obesity, a reduced somatotrop e responsiveness to all GH secretagogues is well known, whereas recent ly, we found that glucose load, but not pirenzepine and somatostatin, fails to inhibit the GHRH-induced GH rise. Thus, the inhibitory effect of hyperglycemia on GH secretion is selectively lacking in obesity. T he aim of the present study was to verify whether in obesity the late stimulatory effect of glucose on GH secretion is preserved. We studied 15 female obese patients (OB; age, 33.9 +/- 2.6 yr; body mass index, 36.4 +/- 1.5 kg/m(2); waist/hip ratio, 0.9 +/- 0.1) and 12 normal fema le subjects (NS; 26.5 +/- 1.0 yr; 21.4 +/- 0.3 kg/m(2)) as controls. T wo studies were performed. In study A (six OB and six NS) we evaluated the somatotrope response to GHRH(1 mu g/kg, iv, at 0 min) alone or pr eceded by oral glucose (OGTT; 100g, orally, at -45 min). In study B (n ine OB and six NS) we studied the somatotrope response to OGTT (100g, orally, at 0 min), saline plusGHRH (1 mu g/kg, iv, at 150 min), and OG TT plus GHRH. In study A, the GHRH-induced GH rise in NS was higher (P < 0.01) than that in OB. OGTT blunted the GHRH-induced GH rise in NS (0-90 min area under the curve, 318.9 +/- 39.1 vs. 696.3 +/- 110.8 mu g/min.L; P < 0.05), but failed to modify it in OB (289.1 +/- 51.7 vs. 283.9 +/- 44.0 mu g/min.L). In study B, the GHRH-induced GH rise in NS was higher (P < 0.01) than that in OB. OGTT induced a late GH increas e in both NS (150-240 min area under the curve, 249.6 +/- 45.2 mu g/mi n.L) and OB (103.2 +/- 31.4 mu g/min.L). Moreover, OGTT enhanced the G HRH-induced GH rise in NS as well as in OB [1433.0 +/- 202.0 vs. 967.9 +/- 116.3 mu g/min.L (P < 0.03) and 763.8 +/- 131.0 us. 278.1 +/- 52. 3 mu g/min.L (P < 0.01), respectively]. The GK responses to OGTT alone and combined with GHRH in OB were lower (P < 0.03) than those in NS. Our data show that in human obesity, the oral glucose load loses its p recocious inhibitory effect on the GHRH-induced GH rise but maintains its late stimulatory effect on somatotrope secretion. These findings s uggest that the inhibitory and stimulatory effects of glucose load on GH secretion are unlikely to be due to biphasic modulation of hypothal amic somatostatin release, which seems selectively refractory to stimu lation by hyperglycemia in obesity.