Intravenous and subcutaneous administration of a long-acting somatostatin analogue: effects on glucose metabolism and splanchnic haemodynamics in healthy subjects

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Abstract
The effect of SMS 201-995, a long-acting somatostatin analogue, on splanchnic blood flow and glucose metabolism, was investigated in five groups of healthy subjects. Groups A (n = 4), B (n = 5), C (n = 5) and D (n = 5) were studied before, during and after a 60-min intravenous infusion of SMS (1.7, 0.8, 0.2 and 0.1 .mu.g min-1, respectively). Group E (n = 6) was investigated before and for 6 h after a subcutaneous injection of 25 .mu.g of SMS. The splanchnic blood flow decreased by 20-25% in all groups in response to SMS and remained low during the entire observation periods. Arterial concentrations of glucose showed a 15-20% decline during SMS infusion in Groups A and B (P < 0.05-0.01) and a less pronounced decrease in the other groups. Fifteen minutes after the end of infusion the glucose levels started to rise and in group A, the levels were significantly higher than basal (+25%, P < 0.05-0.01) at 90-180 min after the end of infusion. The net splanchnic glucose production, determined in groups A and B, decreased by 65-75% in response to SMS infusion. Towards the end and immediately after the infusions, however, the net glucose output increased, but decreased again at 30-60 min after the end of infusion. Arterial, insulin and glucagon concentrations decreased significantly during infusion in all groups. This decline was more pronounced for insulin (50%) than for glucagon (20-25%) and insulin concentrations remained low for a longer period after the end of infusions. After subcutaneous injection both insulin and glucagon levels were low for up to 6 h. Arterial ammonia concentrations decreased and the concentrations of threonine, serine, glutamine, glycine, valine, leucine, phenylalanine, lysine and histidine all rose after i.v. infusion of SMS. It is concluded that SMS exerts a similar, but more prolonged, influence on splanchnic blood flow and the secretion of insulin and glucagon as compared to somatostatin. In addition, the high circulating levels of glucose after the end of infusion, in the face of low splanchnic glucose output, suggests that SMS has a direct effect on peripheral glucose uptake.