Inhibitory regulation of rat exocrine pancreas by peptide YY and pancreatic polypeptide

Abstract

Peptide YY (PYY) and pancreatic polypeptide (PP) have been shown to inhibit exocrine pancreatic secretion in vivo in a variety of species. This study evaluates the type of stimulation inhibited by PYY and PP by examining, in urethan-anesthetized rats, the inhibition of pancreatic secretion when stimulated to a comparable extent by cholecystokinin (CCK), 2-deoxy-D-glucose (2DG), bethanecol, and electrical vagal nerve stimulation. PYY at maximal infusion rates inhibited stimulation by CCK by 83%, bethanecol by 55%, and electrical nerve stimulation by 40%. The inhibition of CCK stimulation was half maximal at 250 pmol.kg-1.h-1. By contrast, PYY totally inhibited 2DG-stimulated secretion with half-maximal inhibition at 10 pmol. kg-1.h-1. PP acted similarly to PYY in inhibiting CCK and 2DG-stimulated pancreatic protein secretion but was fivefold weaker in each case. These findings indicate that PYY and PP have multiple actions but preferentially inhibit neurally mediated pancreatic secretion at a preacinar cell locus, possibly at a central site of action.

Gastric protective effect of peripheral PYY through PYY preferring receptors in anesthetized rats

“…The present study showed 1) that r/pPYY infused intravenously and injected intracisternally exerts a gastroprotective effect against intragastric administration of 45% ethanol-induced mucosal lesions in urethane-anesthetized rats; 2) PYY antibody injected intravenously prevented the gastric protective effect of intravenous but not intracisternal administration of PYY; 3) the gastroprotective action of intravenous PYY is independent of the vagal pathway; and 4) r/p[Pro 34 ]PYY decreased the formation of gastric lesions induced by intragastric administration of 45% ethanol, whereas p[Leu 31 , Pro 34 ]NPY and r/pPYY-(3-36) infused at the same dose had no effect.…”

“…34 ]PYY (75 pmol ⅐ kg Ϫ1 ⅐ h Ϫ1 iv) significantly decreased 45% ethanol-induced gastric lesions to 3.5 Ϯ 1.0% (P Ͻ 0.01) compared with 18.6 Ϯ 3.3% in the intravenous vehicle group. In contrast, p[Leu 31 , Pro 34 ] NPY and r/pPYY-(3-36) infused at the same dose had no effect on gastric lesions (15.9 Ϯ 3.9 and 22.5 Ϯ 4.3%, respectively; Fig. 4).…”

“…Ethanol (45%, 5 ml/kg) was administered intragastrically 30 min after the start of PYY infusion, and rats were euthanized 60 min later to monitor gastric lesions. 34 ]PYY, p[Leu 31 , Pro 34 ]NPY, r/pPYY-(3-36) (75 pmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ), or vehicle (0.1% BSA/ saline) was infused intravenously from 30 min before to 60 min after intragastric administration of ethanol (45%, 5 ml/kg). Rats were euthanized 60 min later, and the gastric lesions were monitored.…”

“…Doses of PYY infused intravenously, reproducing the circulating postprandial peak levels, are in the range of 50-120 pmol ⅐ kg Ϫ1 ⅐ h Ϫ1 in rats (19,34). Intravenous infusion of PYY at doses within this range inhibits stimulated gastric acid secretion (1,16,28,30) and gastric emptying (3,29) in humans and dogs and exocrine pancreatic secretion in rats and dogs (19,31,37) and interrupts intestinal propagation in rats (2). PYY is assumed to act as a physiological inhibitor of upper gastrointestinal functions when nutrients reach the distal small intestine (36).…”

Asymmetrical distribution of δ and PP cells in human pancreatic islets

“…Nevertheless, somatostatin has been shown to inhibit both insulin and glucagon secretions (Schuit et al 1989) and thus participates, albeit indirectly, in glucose homeostasis. Pancreatic polypeptide is mostly involved in satiety (Batterham et al 2003) and in the regulation of pancreatic exocrine secretion (Putnam et al 1989, Morisset 2008, but is known to exhibit some glucose regulatory function as well, for instance by modulating insulin receptor expression in hepatocytes (Seymour et al 1996) and inhibiting glucagon release in mouse pancreatic islets (Aragon et al 2015). It is generally accepted that local interactions between the different islet hormones play fundamental roles in the islet physiology, and some definite interactions are facilitated by the specific positioning of cell types within the islets (Hauge-Evans et al 2009, Unger & Orci 2010, Rodriguez-Diaz et al 2011, Koh et al 2012.…”