Plasma Peptide YY Concentrations Research Articles

Glucagon-Like Peptide-1 7-36 Amide and Peptide YY Have Additive Inhibitory Effect on Gastric Acid Secretion in Man

Background: Glucagon-like peptide-1 7-36 amide (GLP-1) and peptide YY (PYY) are colocalized in the L-cell of the ileal mucosa, and both peptides may function as enterogastrone hormones. However, it is not known whether they interact with regard to the effect on acid secretion. Methods: The effect of intravenous infusion of GLP-1 and PYY, either alone or in combination, on pentagastrin-induced acid secretion in eight healthy volunteers was examined. The peptides were infused at two different rates: 0.25 pmol/kg/min (low rate) and 0.5 pmol/kg/min (high rate). Results: Given alone, GLP-1 and PYY inhibited acid secretion by 26 ± 5% and 18 ± 5% (low rate) and 45 ± 8% and 38 ± 7% (high rate), respectively. Combined infusion resulted in an inhibition of 32 ± 5% (low rate) and 62 ± 7% (high rate). Both infusion rates resulted in GLP-1 and PYY plasma concentrations below or similar to postprandial levels. Conclusion: The present study suggests that the interaction between GLP-1 and PYY in man is of the additive type. The results indicate that GLP-1 and PYY have an important role in the physiologic control of gastric acid secretion.

Ileal release of glucagon-like peptide-1 (GLP-1)

There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II, N = 6), and during endogenous stimulation by intraduodenal essential amino acid perfusion, N = 6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P < 0.01), and endogenously stimulated output by 68%, respectively (P < 0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80-100% (all P < 0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Adrenaline Concentration is Lower in Post-Obese than in Never-Obese Women in the Basal State, in Response to Sham-Feeding and after Food Intake

1. Plasma pancreatic polypeptide, plasma catecholamine, blood glucose, plasma insulin and plasma peptide YY concentrations were studied to assess differences between eight formerly obese and eight never-obese control women during 25 min of sham-feeding (with the sight and smell of an English breakfast) and for 5 h after they had ingested the meal (3514 kJ, 50% fat, 35% carbohydrate). The post-obese women had maintained their normal body weight for at least 3 months before the study. 2. The plasma noradrenaline concentration was not different between the groups either during fasting (post-obese women 0.08 +/- 0.01 ng/ml versus control women 0.10 +/- 0.01 ng/ml) or in the significant postprandial increase (P < 0.001). The plasma adrenaline concentration increased significantly during sham-feeding in the control group from 0.024 +/- 0.004 ng/ml to 0.033 +/- 0.004 ng/ml (P = 0.02) in contrast with the post-obese women, who had significantly lower plasma concentrations of adrenaline in the fasting state (post-obese 0.016 +/- 0.003 ng/ml versus control women 0.024 +/- 0.004 ng/ml, P = 0.003), during sham-feeding (post-obese women 0.018 +/- 0.002 ng/ml versus control women 0.033 +/- 0.004 ng/ml, P = 0.003) and in the postprandial increase (P = 0.003). The maximal postprandial response concentrations recorded 5 h after the meal were 0.025 +/- 0.003 ng/ml in post-obese women and 0.035 +/- 0.004 ng/ml in control subjects (P = 0.04). There were no significant differences in plasma pancreatic polypeptide, plasma peptide YY, plasma insulin, or blood glucose concentrations between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Peptide YY is a physiological regulator of water and electrolyte absorption in the canine small bowel in vivo

Background : Peptide YY (PYY), a hormone released following a meal, is one potential mediator of intestinal absorption. Although PYY inhibits 5′-cyclic adenosine monophosphate (cAMP)-stimulated small intestinal secretion in vitro, its effects on fluid and electrolyte transport in vivo are unknown. Methods : This study examines the effects of physiological doses of PYY in dogs (n = 6) with jejunal and ileal exteriorized, neurovascularly intact intestinal loops (Thiry-Vella fistulas). Results : Plasma PYY levels increased after a meal from 155 ± 15 to 324 ± 26 pmol/L at 30 minutes and remained elevated for 2 hours. PYY infused intravenously in unfed animals at 25, 50, 100, and 200 pmol · kg −1 · h −1, produced a dose-dependent increase in plasma PYY levels. At 100 pmol · kg −1 · h −1, PYY plasma concentrations were similar to those of fed animals (317 ± 39 pmol/L). PYY infusion resulted in a dose-dependent increase in water and electrolyte absorption at all doses in both the jejunum and ileum. Although the relative increase in absorption was similar, the magnitude was greater in the ileum. Conclusions : Physiological concentrations of PYY produced an increase in small bowel absorption of water and electrolytes in vivo. The postprandial release of PYY may mediate the increase in absorption following a meal. Such a proabsorptive agent may have considerable potential for clinical use in malabsorptive states.

Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon.

Peptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.

Fat-induced heal brake in humans: A dose-dependent phenomenon correlated to the plasma levels of peptide YY

Background: Upper gastrointestinal motility is reguated by the presence of nutrients in the distal gut. The present study evaluated whether lipid-induced ileal brake on gastric empting (1) can be elicited by low fat concentrations; (2) is a dose-dependent phenomenon; and (3) is related to gastrointestinal peptide release. Methods: Seven patients were studied in the defunctionalized stage of total colectomy, on three separate occasions. On each study day, patients ate a meal labeled in the solid component; 30 minutes later, one of the following solutions was randomly infused into the ileal pouch: 0.9% saline, 2% oleic acid, and 20% oleic acid. Plasma concentrations of peptide YY (PYY), enteroglucagon, neurotensin, and motilin were measured. Results: Both oleic acid solutions slowed gastric emptying compared with saline (P < 0.001), the effect being dose dependent (P < 0.001). Ileal infusions did not modify neurotensin and enteroglucagon levels but induced a dose-dependent increase of PYY (P < 0.01) and a borderline decrease of motilin (P = 0.05) levels. Slower rates of gastric emptying were related to increased plasma concentrations of PYY (r = 0.615; P < 0.05). Conclusions: This study shows that (1) the ileal brake on gastric emptying can be evoked by low doses of lipids in the distal ileum; (2) the delay of gastric emptying is related to the release of PYY; and (3) both phenomena are dose dependent.

Influence ofin situ neural isolation of jejunoileum on postprandial pancreatobiliary secretion and gastric emptying

Our aims were to examine the influence of neural isolation of the jejunoileum on postprandial pancreatobiliary secretion. In four dogs, duodenal perfusion and aspiration catheters were implanted, and serosal electrodes were placed along the proximal small bowel. Control studies of gastric emptying, output of bile acids and amylase, and plasma concentrations of peptide YY and neurotensin were performed on three occasions following ingestion of a 340-kcal mixed-nutrient liquid meal. The dogs then underwent our model of in situ jejunoileal neural isolation, and the meal studies were repeated. Neural isolation, when compared to control, did not affect either postprandial conversion of intestinal myoelectric activity to the "fed" pattern, gastric emptying (T1/2, X +/- SE of the liquid meal (74 +/- 6 vs 79 +/- 7 min; P greater than 0.05), or cumulative amylase output (373 +/- 59 vs 305 +/- 66 kU; P greater than 0.05). Neural isolation decreased cumulative postprandial bile acid output from 6.6 +/- 0.9 mM to 3.4 +/- 1.1 mM (P less than 0.05) and increased postprandial plasma concentrations of peptide YY and neurotensin. Our findings suggest that the jejunoileal denervation that accompanies the in situ neural isolation of the jejunoileum is not associated with changes in postprandial motility patterns, gastric emptying, or pancreatic amylase secretion. Loss of this innervation, however, may decrease postprandial output of bile acids and lead to a compensatory increase in the postprandial release of neurotensin and peptide YY.

Intracolonic fat inhibits gastric acid secretion independent of gastrin release in the dog

The purpose of this study was to examine the effect of perfusion of the colon with a fatty acid (oleic acid) on peptone-stimulated gastric acid secretion and release of gastrin in conscious dogs. Gastric acid secretion was monitored by continuous intragastric titration. Perfusion of the colon with sodium oleate (24 mmol/hr) inhibited gastric acid secretion (14.2 +/- 2.6 meq/hr) stimulated by a peptone meal (1%) significantly (P less than 0.05) when compared to perfusion of the colon with saline alone (20.1 +/- 1.6 meq/hr). The serum elevation in gastrin in response to intragastric instillation of the peptone meal was not affected by the colonic perfusion of oleic acid. Plasma concentrations of peptide YY (PYY) increased significantly in response to perfusion of the colon with saline or sodium oleate, and the integrated release of PYY in response to sodium oleate [6.9 +/- 2.8 ng (60-120) min/ml] was significantly greater than the response to saline [3.1 +/- 0.7 ng (60-120) min/ml]. The results of this study indicate that inhibition of gastric acid secretion by perfusion of the colon with fat is not due to an inhibition of gastrin release. In addition, because PYY is an inhibitor of gastric acid secretion, it is possible that PYY participates as an inhibitor of gastric acid secretion by the colon.

Elevated plasma peptide YY in human neonates and infants.

Plasma concentrations of peptide YY (PYY) were measured in cord blood and at 6, 12, and 18 days of postnatal life in 24 healthy preterm neonates, from cord blood of eight full-term neonates, and from peripheral blood of 13 infants 9 months old. Concentrations were high in cord blood (73 +/- 9 pmol/liter versus adult fasting 10.4 +/- 1.3, p less than 0.001) and rose postnatally in the premature infants to 399 +/- 48 pmol/liter at 6 days, 489 +/- 42 at 12 days, and fell to 414 +/- 43 at 18 days. Plasma PYY concentrations were much lower in infants 9 months old (32 +/- 3 pmol/liter), suggesting that the postnatal surge of plasma PYY is a feature of early adaptation to extrauterine life. Gel permeation chromatograms revealed that the major circulating form of PYY in the neonate eluted in a position identical to that of the pure 36 amino acid peptide. There was, however, evidence of two larger molecular forms that may be precursor molecules. Because PYY is a peptide that exhibits potent effects on gastrointestinal secretion and motility in humans, these observations suggest that this candidate gut hormone may be important in the adaptation to enteral nutrition in the neonate.

Peptide YY abnormalities in gastrointestinal diseases

Plasma concentrations of peptide YY (PYY), a newly isolated peptide produced by ileal and colonic endocrine cells, were measured in several groups of patients with digestive disorders after a standardized normal breakfast. Peptide YY levels were found to be grossly elevated in patients with steatorrhea due to small intestinal mucosal atrophy (tropical sprue). Basal levels in these patients were 79 ± 18 pM, which was nearly 10-fold higher than those seen in healthy controls (8.5 ± 0.8 pM). Patients with steatorrhea due to chronic destructive pancreatitis also had substantially increased basal PYY levels (47.5 ± 6.3 pM), and their postprandial response was also greater than that of normal subjects. Moderately elevated plasma PYY concentrations were seen in patients with inflammatory bowel disease and patients recovering from acute infective diarrhea. In contrast, patients with diverticular disease, duodenal ulcer, and functional bowel disease had normal PYY responses. These changes in the secretion of PYY, which appear to result from malabsorption, may shed light on the physiologic role of this newly discovered peptide and on intestinal adaptation to common digestive disorders.