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Suppression of growth hormone by means of somatostatin has been suggested as a possible adjunct therapy in Type 1 diabetes. To assess the acute effect of the somatostatin analogue SMS 201-995 on kidney function in uncomplicated Type 1 diabetes, 13 normoalbuminuric, normotensive diabetic patients were investigated before and during IV infusion of SMS 201-995 (8 micrograms h-1). A control experiment with infusion of carrier only was also performed. The SMS infusion induced a reduction in the glomerular filtration rate (clearance of 125I-iothalamate) and renal plasma flow (131I-hippuran) from 140 +/- 15 (mean +/- SD) and 550 +/- 69 to 131 +/- 14 (2p less than 0.005) and 492 +/- 73 ml min-1 1.73-m-2 (2p less than 0.001), while filtration fraction and total renal resistance rose (both 2p less than 0.001). Urinary albumin excretion rate, blood pressure, and blood glucose concentration were unchanged. Plasma growth hormone and glucagon were significantly suppressed. The reduction in glomerular filtration rate and renal plasma flow correlated with the fall in glucagon concentration (r = 0.57, 2p = 0.04, and r = 0.63, 2p = 0.02). The urinary flow rate was markedly reduced, urine osmolality increased, and fractional excretion of sodium, calcium, and phosphate were reduced. Arginine vasopressin, atrial natriuretic peptide, angiotensin II, and aldosterone were unchanged by the SMS infusion. Thus SMS 201-995 acutely reduces glomerular filtration rate and renal plasma flow in uncomplicated Type 1 diabetes and has an antidiuretic effect. The effects may be related to suppression of glucagon secretion.

The influence of somatostatin (a bolus injection of 250 micrograms i.v. followed by 6 micrograms/min for 40 min) on the plasma cyclic AMP, insulin, glucose and non-esterified fatty acid (NEFA) responses to i.v. adrenaline (0.07 micrograms/kg body-weight/min for 20 min) and the plasma cyclic AMP, insulin and glucose responses to a bolus injection of i.v. glucagon (0.01 mg/kg BW) were studied in normal subjects. Somatostatin suppressed the insulin response to glucagon and inhibited the insulin rebound observed on termination of adrenaline infusion. The plasma glucose response to glucagon was exaggerated by somatostatin, reflecting insulin deficiency. Neither the plasma glucose or plasma non-esterified fatty acid responses to adrenaline were influenced by somatostatin. Adrenaline produced a three-fold and glucagon a twenty-fold rise in plasma cyclic AMP and 15 min. This was not influenced by concurrent somatostatin infusion, indicating that somatostatin is not a universal inhibitor of hormone stimulated adenylate cyclase activity. This is supported by the failure of somatostatin to inhibit the metabolic actions of glucagon and adrenaline thought to be mediated by cyclic AMP.

Injection of somatostatin, the hypothalamic growth-hormone-inhibiting factor, lowered basal plasma-insulin levels. In intravenous glucose-tolerance tests in five normal subjects, glucose-induced insulin release was markedly suppressed and the glucose-disappearance rate was lowered after somatostatin. Perfusion experiments on the isolated canine pancreas showed that somatostatin acts directly on the beta cells, causing suppression of the initial and the late sustained insulin release phase.