These studies were designed to elucidate the mechanism of inhibitory action of somatostatin (SRIF) on glucagon (IRG) and insulin (IRI) secretion. Studies were carried out in the unrecirculated isolated rat pancreas perfusion with arginine 19.2 mM and glucose 5.5 mM as stimulus primarily for IRG but also IRI secretion. The effects of excess Ca ++ (15.2 mEq/L) and excess K + (12.8 mEq/L) on IRG, IRI, and the SRIF inhibited pancreas were studied. Ca ++ excess in 5 perfusions strikingly stimulated IRG secretion (+92%) but only stabilized IRI secretion compared with control perfusions. K + excess (in 7 perfusions) markedly inhibited IRG secretion (-39%) while stimulating IRI secretion (+16%). Restoration of normal concentration of K + resulted in a rebound of IRG to levels 120% that of controls. SRIF, at concentrations from 0.1 to 20 ng/ml, produced inhibition of both IRG and IRI. In 11 perfusions, with SRIF at 10 ng/ml, IRG decreased more than IRI (-75.2% IRG and -46.9% IRI). In 5 perfusions, addition of Ca ++ (15.2 mEq/l) 10 min after SRIF was started resulted in a reversal of IRG inhibition to 69.4% and IRI to 73.2% of the arginine controls. The reversal by Ca ++ of SRIF effect on IRG was greater at higher concentrations of Ca ++, suggesting some form of competition. In 4 perfusions, excess K + reversed SRIF induced IRI inhibition. Studies in vitro with isolated islets revealed that SRIF (2 μg/ml) inhibited 45Ca uptake of islets as did epinephrine (10 -5 M). It was concluded that SRIF induced inhibition of hormone release appears related to an action on Ca ++ uptake.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism