Opposite effects of bombesin on insulin and gastrin response to food in humans.

Abstract

SUMMARY The effect of bombesin on insulin and gastrin response to a standard labelled meal was studied in eight healthy male volunteers. The gastric emptying of solids was simultaneously evaluated. During intravenous infusion of the peptide (5 ng/kg/min) the insulin release after eating was greatly reduced whereas food stimulated gastrin release was significantly enhanced. Both effects of bombesin are likely to be connected with the marked inhibition of gastric emptying induced by the peptide.Bombesin is a frog skin tetradecapeptide which has been found to have similar immunologically charactensed counterparts in mammalian gut. 1-3 An heptacosapeptide has been isolated from porcine non-antral gastric tissue: the so called gastrin releasing peptide (GRP).4 The homology of its C-terminal decapeptide with C-terminal decapeptide of bombesin is impressive. As a consequence, both these peptides have the same spectrum of biological actions, although some qualitative differences have been reported.Many radioimmunological and immunocytochemical observations indicate that bombesin like peptides are confined to neurones and fibres of the intramural plexus of the gUt.6 7 As a consequence, they have been put forward as putative neurotransmitters in mammalian gut.Bombesin was shown to be a potent and polivalent releaser of several gastrointestinal hormones both in animals and humans.8 Its gastrin releasing effect, first demonstrated in dogs, was repeatedly confirmed in other animal species including man.8 10 On the contrary, results concerning its effect on insulin secretion have been contradictory. A stimulation of insulin release was observed in dogs," cats,12 and man13 14 whereas an inhibition was reported in rats.'5 In vitro studies have provided conflicting results, as well. In fact, whereas bombesin stimulates insulin secretion in isolated and perfused pancreas from dogs'6 and rats17 it inhibits the hormone release from isolated rat pancreatic islets.'8 The recent discovery of bombesin like immunoreactivity in the human pancreas13 suggests that this peptide may also affect human pancreatic secretion. Therefore we decided to study in man its effect on insulin response to food. Because bombesin was shown to affect gastric emptying,19 the effect of the peptide on emptying rate was simultaneously evaluated.Preliminary results of the present investigation have been presented at the Italian Society of Gastroenterology (June 1981) and appeared in abstract form. Methods

Effect of Bombesin on Glucose-Induced Insulin Release in Humans

“…This finding was not unexpected, taking into account our previous results con cerning meal-stimulated insulin release [41], The lack of postprandial hyperglycemia and the consequent inhibition of insulin release are likely to be connected with the strong inhibition of gastric emptying, the delay of which slows the entry of glucose into the small bowel. In accordance with our results, Salera et al [39] recently reported that dur ing bombesin administration to healthy vol unteers, the oral glucose load was followed by a flattened glucose curve and a significant inhibition of insulin release.…”

“…In this investigation, the delaying effect ex erted on the gastric emptying of liquids (glu cose solution) by bombesin was confirmed using a different (radioisotopic) technique. Looking at the emptying half-times for solids (previously obtained [41]) and liquids (re ported here), one can realize that the effects exerted by the peptide on the gastric emptying of liquids and solids are equally important, and this suggests that both the proximal and the distal stomach are involved in the action of bombesin on gastric emptying [31]. Although no effect on basal insulin levels was observed after bombesin administra tion, a clear-cut enhancement of insulin re lease was evident when glucose was injected intravenously.…”

“…In a previous paper [41] we studied the effect of bombesin on the insulin response to food in humans and found that the meal-induced insulin re lease was markedly inhibited when bombe sin was infused intravenously. This effect was indirect and connected with the marked inhibition of gastric emptying induced by the peptide [41,44], In this investigation, the effect of bombesin on insulin levels was studied in healthy volunteers to whom glu cose was administered by oral or intrave nous route. In addition, an intraduodenal glucose load was used as a stimulus for insu lin release in order to exclude the bombesin effect on gastric emptying.…”

Different effects of bombesin on glucose‐ and tolbutamide‐induced insulin release in man

“…In previous papers, we have shown that bombesin affects the insulin response to mixed meal (Scarpignato & Micali, 1986) and to oral as well as intravenous glucose load (Scarpignato et al, 1987b). However, no effect on basal insulin levels was observed.…”

Bombesin - The Most Stimulating Peptide of Human Gastric Smooth Muscle

“…(2) Bombe sin delays gastric emptying [11][12][13]. Many of the effects of bombesin on motility appear to be indirectly mediated and bombesin may be an excitatory transmitter of an enteric inter neuron.…”