Meal‐induced peptide tyrosine tyrosine inhibition of pancreatic secretion in the rat

Abstract

In the present studies we examined the distribution, release, and biological actions of peptide tyrosine tyrosine (PYY) in the rat. The concentration and distribution of PYY was highest in the ileum and colon as determined by both radioimmunoassay of rat tissue extracts and immunocytochemistry. An ultrastructural comparison of rat and dog colonic PYY cells revealed a bipolar distribution of peptide-containing secretory granules in both species. Serum PYY and pancreatic exocrine secretory responses were monitored after presentation of a meal to meal-trained rats (n = 12). A significant increase in PYY concentrations was not observed until 120 min after meal presentation, a delayed response similar to that previously observed in the dog. PYY responses were also observed in rats after perfusion of the intestine at the level of the duodenum and ileum with an 80 mOsm micellar solution of sodium oleate. Duodenal instillations of the fatty acids resulted in a maximum PYY response after 120 min, whereas rats subject to ileal perfusion of fat exhibited maximum PYY release within the first hour. In other experiments, infusion of exogenous PYY at 100 pmol.kg-1.h-1, which reproduced plasma PYY levels observed after a meal and perfusion of the gut with fat, significantly inhibited CCK-stimulated bile pancreatic volume (P less than 0.02), protein (P less than 0.01), and amylase (P less than 0.01) output. These studies demonstrate a bipolar distribution of PYY-containing secretory granules in cells of the jejunal, ileal, and colonic mucosa, and show that PYY is released in response to a meal in amounts sufficient to inhibit cholecystokinin-stimulated pancreatic secretion. Evidence is presented that PYY may mediate the delayed inhibition of pancreatic secretion that is observed in the rat after ingestion of a meal.

Peptide YY and Neuropeptide Y Induce Villin Expression, Reduce Adhesion, and Enhance Migration in Small Intestinal Cells through the Regulation of CD63, Matrix Metalloproteinase-3, and Cdc42 Activity

“…Concomitantly, PYY induces I-FABP in hBRIE 380i cells at a concentration and time course similar to those of PYY release in vivo in response to a meal (62). This suggests that nutrients such as long chain free fatty acids cause the endocrine release of PYY or the vagal release of NPY, leading to the activation of Y FIG.…”

Evidence for a Role of the Gut Hormone PYY in the Regulation of Intestinal Fatty Acid-binding Protein Transcripts in Differentiated Subpopulations of Intestinal Epithelial Cell Hybrids

“…These preliminary data demonstrated a maximal increase in mRNA of 1.35 Ϯ 1.23-fold (n ϭ 3) when the cells were incubated with 100 nM PYY for 6 h (Fig. 1B and Table I), a dose within the physiological range (12). Although the changes in mRNA levels were found to be consistently elevated after 6 h treatment, this increase in transcript expression level was too small when compared with control values to be of statistical significance.…”

“…The fusion protein was isolated from bacterial lysates by glutathione-Sepharose 4B affinity chromatography, eluted, and cleaved by the addition of thrombin (2980 units/mg) (Sigma) according to methods of the manufacturer. Isolated I-FABP was coupled to keyhole limpet hemocyanin (Sigma) using 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide (Sigma) according to the procedure described previously (12). Three guinea pigs were injected subcutaneously with the protein conjugate, corresponding to 40 g of protein per injection by methods described previously (33).…”

“…Tissue samples from the lower duodenum-upper ileum (50 cm from the pylorus) of the rat small intestine was prepared as described previously (12). The intestinal tissue segments (3-6 cm) were placed in fixative (4% paraformaldehyde in PBS, pH 7.4) for 3 h at 4°C.…”

“…Many of the reported effects of PYY on the gut, such as the inhibition of intestinal secretion, motility, and gastric acid secretion, occur as interdigestive events coordinated with release of PYY after a meal. We and others have demonstrated that luminal oleic acid induces the release of PYY in the dog (11), rat (12), and in isolated primary cultured PYY cells from the canine mucosa (13). Although it has been proposed that NPY acts centrally to initiate feeding (14), PYY seems to modify digestive processes to ensure efficient utilization of ingested food.…”