Somatostatin: Central nervous system (CNS) action on glucoregulation

Abstract

Somatostatin (SRIF) may potentially affect blood glucose concentrations by a variety of mechanisms. SRIF could alter hepatic glucose output by a direct effect on the liver 1 or by an effect on pancreatic insulin and glucagon secretion, which in turn could alter hepatic glucose output. 2 SRIF can also affect the pituitary secretion of growth hormone, which secondarily might alter blood glucose levels. Recently Unger et al. 3 have suggested that SRIF may play a role in controlling nutrient entry from the gut. The anatomic distribution of SRIF throughout the central nervous system (CNS) and gastrointestinal tract and the multiple potential sites of action of SRIF to affect glucoregulation at extra-CNS sites provide a rationale for questioning whether or not there are glucoregulatory sites of action of SRIF within the CNS. Since the studies of Bernard demonstrating that puncture of the floor of the fourth ventricle produced hyperglycemia, evidence has accumulated to support CNS control of glucose homeostasis. 4 We have recently demonstrated that the frog skin peptide, bombesin, when placed intracisternally (i.c.) evokes a rapid and sustained hyperglycemia in rats. 5 This action of bombesin was concluded to be mediated via the CNS since bombesin is 10,000 times more potent in producing hyperglycemia when given i.c. than when given intravenously (i.v.). 5 These findings provided a model in which to test whether or not SRIF could prevent the hyperglycemic action of bombesin and thus test whether or not SRIF might have glucoregulatory sites of action within the CNS. Bombesin is a tetradecapeptide isolated from the skin of the frog Bombina bombina. 6 Bombesin-like activity has been found in mammalian intestine 7–9 and brain 10,11 as determined by radioimmunoassay. Bombesin has been reported to have the following effects: increase blood pressure; stimulate the secretion of gastric acid, gastrin, and cholecystokinin; stimulate exocrine pancreatic secretion; and produce contraction of the gall bladder. 8 In addition, bombesin and bombesin-like peptides affect the CNS to lower body temperature, 12 to inhibit cold-induced thyrotropin secretion, 10 and to stimulate the secretion of growth hormone and prolactin 13 in the rat.