gastrin-releasing-peptide and Hyperglycemia

Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.

Topics: Amylases; Animals; Bombesin; DNA; Food, Formulated; Gastrin-Releasing Peptide; Gene Expression Regulation; Hyperglycemia; Islets of Langerhans; Lipase; Male; Mice; Mice, Inbred ICR; Pancreas, Exocrine; Pancreatic Hormones; Parenteral Nutrition

Gastrin-releasing peptide (GRP) mediated signals in the central nervous system (CNS) influence many functions associated with energy metabolism. The purpose of the present study was to investigate the central effect of GRP on glucose metabolism in the male rat. Intracerebroventricular (icv) administration of GRP caused an immediate hyperglycaemia which was sustained till the end of the infusion. The rise in plasma glucose levels was accompanied by an increase in endogenous glucose production (EGP), as well as increases in plasma glucagon and insulin concentrations. Furthermore, no differences in plasma corticosterone levels were noted between control and GRP treated rats. These results demonstrate that central GRP increases plasma glucose levels, probably by stimulating pancreatic glucagon release and concomitantly or subsequently endogenous glucose production.

Topics: Analysis of Variance; Animals; Blood Glucose; Corticosterone; Gastrin-Releasing Peptide; Gastrointestinal Agents; Glucagon; Humans; Hyperglycemia; Injections, Intraventricular; Insulin; Male; Rats; Rats, Wistar; Time Factors