Reduced Postprandial Hyperglycemia After Subcutaneous Injection of a Somatostatin-Analogue (SMS 201-995) in Insulin-dependent Diabetes Mellitus

Abstract

The effect of a new octapeptide analogue of somatostatin (SMS 201-995) on blood glucose and gut hormone levels was studied in 10 C-peptide-negative, insulin-dependent diabetic (IDDM) subjects. On separate days, either 50 or 100 μg SMS or placebo was s.c. injected simultaneously with an identical insulin dose 30 min before a mixed meal. Postprandial blood glucose decreased after 100 μg SMS s.c. within 30 min from 8.9 ± 0.7 to 7.8 ± 0.6 mmol/L (P < 0.001) and remained at similar levels during 180 min. In contrast, postprandial blood glucose concentration increased after placebo from 9.9 ± 0.8 to 13.8 ± 0.9 mmol/L (SMS versus placebo P < 0.001). Plasma glucagon decreased rapidly after SMS to the limit of detection (P < 0.001) and remained lowered during 180 min; in contrast, glucagon levels increased after the meal during the placebo study (SMS versus placebo P < 0.001). Plasma growth hormone concentrations were significantly lower after SMS than after placebo (P < 0.05). SMS abolished completely the postprandial increase in plasma gastrin and pancreatic polypeptide (PP) concentrations. Plasma free fatty acid (FFA) and triglyceride concentrations decreased after SMS, reaching significantly lower levels than after placebo (P < 0.05 and P < 0.01), respectively). Plasma SMS concentration increased rapidly after s.c. administration of SMS; its appearance preceded that of plasma free insulin after s.c. insulin injection. Fifty micrograms SMS was similarly effective as 100 μg in decreasing blood glucose, triglycerides, glucagon, and gut hormone concentrations. The data demonstrate that in contrast to native somatostatin whose action is known to be relatively weak and shortlived after s.c. administration, this somatostatin analogue results in diminished postprandial blood glucose and plasma triglyceride concentrations and in prolonged suppression of gut hormone levels after s.c. injection.