Enteroglucagon

Abstract: Incretins are intestinal factors that stimulate postprandial insulin secretion in preparation for subsequent rises in plasma levels of ingested nutrients. Glucose-dependent insulinotropic peptide (GIP), a duodenal endocrine peptide, is ideally located for such a function. In contrast, the intestinal proglucagon-derived peptide (PGDP), truncated GLP-1 [GLP-1(7-37) or tGLP-1] is equipotent to GIP in insulinotropic activity, but due to its localization in the distal ileum, appears to be poorly situated to fulfill an incretin role in response to direct nutrient stimulation. Despite its distribution, rapid increments in plasma levels of tGLP-1 have been noted in response to nutrient ingestion. We have recently reported that GIP (but not other nutrient-stimulated duodenal endocrine peptides) can stimulate intestinal PGDP secretion in vitro, and therefore hypothesized that GIP might regulate secretion of the intestinal PGDPs, including tGLP-1, in response to nutrient ingestion in vivo in the rat. Placement of either fat or glucose directly into the ileal lumen was demonstrated to significantly stimulate secretion of the intestinal PGDPs (P < 0.05), whereas fat or glucose in the duodenal lumen significantly increased plasma levels of GIP (P < 0.05). In addition, however, duodenal fat treatment also increased the secretion of intestinal PGDPs into the circulation (P < 0.05), with levels rising to same extent as observed after direct administration of fat into the ileum. The rise in plasma GIP levels in response to duodenal fat treatment occurred slightly before the increments in intestinal PGDP levels, suggesting a relationship between the two peptides. Intravenous infusion of GIP to give concentrations similar to those observed after duodenal fat administration induced a 2-fold increase in plasma levels of intestinal PGDPs that was independent of glycemic levels (P < 0.05). No increment in intestinal PGDPs was found in response to infusion of another duodenal endocrine peptide, cholecystokinin. Thus, these data demonstrate a specific effect of GIP to stimulate secretion of the intestinal PGDPs in vivo in the rat. This enteroendocrine loop between the duodenal peptide GIP and the ileal PGDPs may account for some of the early rises in secretion of tGLP-1 observed in response to nutrient ingestion.

Abstract: . Previously we have identified multiple surges in plasma concentrations of gut hormones post-natally in enterally fed term and preterm infants. In this study on 104 preterm infants we have shown that such surges are induced after ingestion of very small quantities of human milk. Whereas 6-day-old exclusively parenterally fed infants showed no postnatal elevation in enteroglucagon, gastrin, GIP, motilin and neurotensin, infants recovering from hyaline membrane disease who had received restricted enteral nutrition had similar hormone surges to those seen in well infants on full enteral feeds. Significant elevations in enteroglucagon, gastrin and GIP occurred after a cumulative mean enteral feed volume since birth of only 24 ml (12 ml/kg body weight) had been consumed and after a mean total intake of 96 ml (50 ml/kg) the response was maximal. Greater feed volumes were required to produce a neurotensin or motilin surge, but even these volumes were substantially lower than those required for full enteral feeding. In view of the proposed roles of gut hormones in the adaptation to extrauterine nutrition these data have implications for mammalian biology and raise the possibility that ‘minimal enteral feeding’ might have a clinical therapeutic role in infants undergoing prolonged parenteral nutrition.