EFFECTS OF THE NEW SOMATOSTATIN ANALOG (BIM-23014) ON BLOOD-GLUCOSE HOMEOSTASIS IN NORMAL MEN

Changes in blood glucose homeostasis induced by the new somatostatin analogue BIM 23014 (BIM) were studied. Eight normal men (study 1) received either vehicle or 1000, 2000 and 3000 mug BIM as a 24 h s.c. infusion. Blood glucose, plasma insulin, C-peptide, glucagon and growth hormone (GH) were measured before treatment and then hourly for 24 h. In five normal men (study 2) an oral glucose tolerance test (OGTT) was performed during vehicle infusion and then on days 1 and 7 of a continuous s.c. infusion of 2000 mug BIM daily for 7 days. The same biological parameters as in study 1 were measured before OGTT and then twice-hourly for 5 h. Dose-dependent and transient glucose intolerance was observed in the first half of study 1. Except for glucagon, BIM significantly (P < 0.01) reduced plasma insulin, C-peptide and GH levels. In study 2 BIM infusion induced glucose intolerance and a drop in plasma insulin and C-peptide on day 1 which disappeared on day 7 of infusion. Higher on day 7 than on day 1, plasma GH secretion was significantly (P < 0.01) reduced throughout BIM infusion. In contrast plasma glucagon levels were not modified at any time. Side-effects were abdominal cramps and diarrhoea which were observed in most subjects when increasing BIM daily dose. In conclusion, BIM infusion induced transient changes in glucose homeostasis and insulin secretion in normal men. By contrast, plasma GH levels remained reduced throughout the treatment. BIM appears to be a useful tool to selectively inhibit GH secretion.