Summary
In order to investigate the action of somatostatin-28 (SS-28) on the metabolic homeostasis of insulin-dependent diabetics, we compared its effects to those of somatostatin-14 (SS-14) in terms of insulin sparing, changes in dextrose demands, glucose fluctuations and behavior of growth hormone and glucagon secretion. Eight insulin-dependent subjects were connected to Artificial Endocrine Pancreas (Biostator®) for 84 hours during which they received intravenous infusions of either SS-14, SS-28 or isotonic saline in a randomized order, after a steady state of metabolism had been achieved. Five of the patients received SS-28 100 μg/h and SS-14 250 μg/h for 10 hours and three of them SS-28, 50 μg/h and SS-14 250 μg/h for 12 hours. Identical doses of both peptides were administered as bolus infusions prior to the continuous ones. Under SS-28 100 μg/h and SS-14 250 μg/h patients required 13.5±2.3 and 14.5±1.9 U of insulin respectively vs 40±5.6 U under isotonic saline infusion (mean±SEM, P < 0.005 and P < 0.01). At the same period the apparatus delivered 15 times more dextrose under SS-28 and 20 times more under SS-14. The magnitude of glucose fluctuations diminished from 64.6±2.47 mg% without to 41.4±2 mg% under SS-14 (P < 0.01) and 46±3.8 mg% under SS-28 (P < 0.02). Similar changes were observed in the remaining three patients who received SS-28 in the dose of 50 μg/h. Glucagon secretion was not inhibited in none of the cases by SS-14, whereas SS-28 caused a 50% inhibition. Growth hormone secretion was inhibited by almost 50% under SS-14 and completely under SS-28 (100 μg/h). These findings demonstrate that SS-28 presents at least double potency in comparison to SS-14 as far as decrease of insulin requirements in insulin-dependent diabetics is concerned and definitely stronger action in regard to smoothening of glucose curve, increase in dextrose demands and inhibition of hyperglycaemic hormones such as glucagon and growth hormone. Conceivably the octacosapeptide probably represents the main hormone, while the tetradecapeptide just a fragment of it.
Key-Words
Somatostatin-14
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Somatostatin-28
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Diabetes Mellitus
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Artificial Pancreas
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Growth Hormone
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Glucagon
