peptide-yy and Diarrhea

Inhibition of diacylglycerol acyltransferase 1 (DGAT1) is a potential treatment modality for patients with type 2 diabetes mellitus and obesity, based on preclinical data suggesting it is associated with insulin sensitization and weight loss. This randomized, placebo-controlled, phase 1 study in 62 overweight or obese men explored the effects and tolerability of AZD7687, a reversible and selective DGAT1 inhibitor.. Multiple doses of AZD7687 (1, 2.5, 5, 10 and 20 mg/day, n = 6 or n = 12 for each) or placebo (n = 20) were administered for 1 week. Postprandial serum triacylglycerol (TAG) was measured for 8 h after a standardized 45% fat meal. Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured and a paracetamol challenge was performed to assess gastric emptying.. Dose-dependent reductions in postprandial serum TAG were demonstrated with AZD7687 doses ≥5 mg compared with placebo (p < 0.01). Significant (p < 0.001) increases in plasma GLP-1 and PYY levels were seen at these doses, but no clear effect on gastric emptying was demonstrated at the end of treatment. With AZD7687 doses >5 mg/day, gastrointestinal (GI) side effects increased; 11/18 of these participants discontinued treatment owing to diarrhoea.. Altered lipid handling and hormone secretion in the gut were demonstrated during 1-week treatment with the DGAT1 inhibitor AZD7687. However, the apparent lack of therapeutic window owing to GI side effects of AZD7687, particularly diarrhoea, makes the utility of DGAT1 inhibition as a novel treatment for diabetes and obesity questionable.

Topics: Acetates; Adult; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Diacylglycerol O-Acyltransferase; Diarrhea; Dose-Response Relationship, Drug; Gastric Emptying; Glucagon-Like Peptide 1; Humans; Intestinal Absorption; Male; Middle Aged; Obesity; Peptide YY; Pyrazines; Treatment Outcome; Weight Loss

Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood.. We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS.. Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined.. Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group.. Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.

Topics: Adult; Analysis of Variance; Case-Control Studies; Catheterization; Cholecystokinin; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Dietary Fats; Female; Humans; Male; Middle Aged; Motilin; Neuropeptide Y; Pain Threshold; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Pressure; Statistics, Nonparametric; Stomach; Vasoactive Intestinal Peptide

We investigated the effect of acarbose, an alpha-glucosidase and pancreatic alpha-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 (r = 0.68, P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.

Topics: Acarbose; Administration, Oral; Adult; Area Under Curve; Blood Glucose; Cholecystokinin; Diarrhea; Dietary Carbohydrates; Energy Intake; Enzyme Inhibitors; Flatulence; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Male; Peptide Fragments; Peptide YY; Protein Precursors; Sucrose

Previous studies showed increased plasma motilin and substance P concentrations and accelerated motor function in the small bowel and colon in patients with carcinoid diarrhea. Octreotide is beneficial in patients with carcinoid syndrome. Our hypothesis was that octreotide inhibits accelerated motility and gut neuropeptides in carcinoid syndrome.. In 12 patients with metastatic carcinoid syndrome, we investigated the effect of octreotide 50 microg s.c. t.i.d (n = 6) or placebo (n = 6) on postprandial symptoms, GI transit, colonic motility, and circulating levels of selected circulating peptides and amines.. Octreotide reduced postprandial flushing (p = 0.03) but not pain. Octreotide significantly retarded overall colonic transit and proximal colonic emptying (p < 0.05); it tended to prolong small bowel transit time (p = 0.13) and to reduce postprandial colonic tone (p = 0.08) compared with placebo. Octreotide also reduced circulating levels of peptide YY, neurotensin, vasoactive intestinal polypeptide, and substance P but had no effect on plasma motilin, neuropeptide Y, calcitonin gene-related peptide, or histamine after meal ingestion.. Octreotide ameliorates gut motor dysfunctions that characterize carcinoid diarrhea; the potential role of specific antagonism of serotonin, substance P, and vasoactive intestinal polypeptide alone or in combination with agents that inhibit their release in carcinoid diarrhea deserves further study.

Topics: Aged; Antineoplastic Agents, Hormonal; Calcitonin Gene-Related Peptide; Colon; Colonic Diseases; Diarrhea; Digestion; Double-Blind Method; Female; Flushing; Gastrointestinal Agents; Gastrointestinal Motility; Gastrointestinal Transit; Histamine; Humans; Intestine, Small; Male; Malignant Carcinoid Syndrome; Middle Aged; Motilin; Neuropeptide Y; Neuropeptides; Neurotensin; Octreotide; Peptide YY; Placebos; Serotonin Antagonists; Substance P; Vasoactive Intestinal Peptide

The consumption of contaminated shellfish with okadaic acid (OA) group of toxins leads to diarrhoeic shellfish poisoning (DSP) characterized by a set of symptoms including nausea, vomiting and diarrhoea. These phycotoxins are Ser/Thr phosphatase inhibitors, which produce hyperphosphorylation in cellular proteins. However, this inhibition does not fully explain the symptomatology reported and other targets could be relevant to the toxicity. Previous studies have indicated a feasible involvement of the nervous system. We performed a set of in vivo approaches to elucidate whether neuropeptide Y (NPY), Peptide YY (PYY) or serotonin (5-HT) was implicated in the early OA-induced diarrhoea. Fasted Swiss female mice were administered NPY, PYY(3-36) or cyproheptadine intraperitoneal prior to oral OA treatment (250 µg/kg). A non-significant delay in diarrhoea onset was observed for NPY (107 µg/kg) and PYY(3-36) (1 mg/kg) pre-treatment. On the contrary, the serotonin antagonist cyproheptadine was able to block (10 mg/kg) or delay (0.1 and 1 mg/kg) diarrhoea onset suggesting a role of 5-HT. This is the first report of the possible involvement of serotonin in OA-induced poisoning.

Topics: Animals; Cyproheptadine; Diarrhea; Enzyme Inhibitors; Female; Mice; Neuropeptide Y; Okadaic Acid; Peptide Fragments; Peptide YY; Serotonin; Serotonin Antagonists; Shellfish Poisoning; Time Factors

To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients.. Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software.. The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 ± 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 ± 0.4, 6.6 ± 0.4, and 7.2 ± 0.4, respectively. The density of serotonin cells in the ileum was 40.6 ± 3.6 cells/mm² in the controls, and 11.5 ± 1.2, 10.7 ± 5.6, 10.0 ± 1.9, and 13.9 ± 1.4 cells/mm² in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P < 0.0001, P = 0.0001, P = 0.0001, and P < 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 ± 1.6 cells/mm(2) in the controls, and 33.1 ± 1.4, 27.5 ± 1.4, 34.1 ± 2.5, and 41.7 ± 3.1 cells/mm² in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and < 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells.. The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.

Topics: Adolescent; Adult; Aged; Biomarkers; Biopsy; Case-Control Studies; Colonoscopy; Constipation; Diarrhea; Endocrine Cells; Female; Glucagon-Like Peptides; Humans; Hyperalgesia; Ileum; Image Interpretation, Computer-Assisted; Immunohistochemistry; Irritable Bowel Syndrome; Male; Middle Aged; Pain Measurement; Pancreatic Polypeptide; Peptide YY; Serotonin; Somatostatin; Somatostatin-Secreting Cells; Surveys and Questionnaires; Visceral Pain; Young Adult

The gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients.. To investigate a possible abnormality in the colonic endocrine cells of IBS patients.. A total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis.. Serotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin-immunoreactive cells were too few to enable reliable quantification.. The cause of these observations could be primary genetic defect(s), secondary to altered serotonin and/or PYY signaling systems and/or subclinical inflammation. Serotonin activates the submucosal sensory branch of the enteric nervous system and controls gastrointestinal motility and chloride secretion via interneurons and motor neurons. PYY stimulates absorption of water and electrolytes, and inhibits prostaglandin (PG) E2, and vasoactive intestinal peptide, which stimulates intestinal fluid secretion and is a major regulator of the "ileal brake". Although the cause and effect relationship of these findings is difficult to elucidate, the abnormalities reported here might contribute to the symptoms associated with IBS.

Topics: Adolescent; Adult; Aged; Colon; Constipation; Diarrhea; Female; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Peptide YY; Serotonin; Young Adult

Peptide YY (PYY) antisecretory effect on intestinal epithelia is well established, whereas less is known about its actions to influence colonic motility in conscious animals. We characterized changes in basal function and stimulated colonic motor function induced by PYY-related peptides in conscious mice. PYY(3-36), PYY, and neuropeptide Y (NPY) (8 nmol/kg) injected intraperitoneally inhibited fecal pellet output (FPO) per hour during novel environment stress by 90%, 63%, and 57%, respectively, whereas the Y(1)-preferring agonists, [Pro(34)]PYY and [Leu(31),Pro(34)]NPY, had no effect. Corticotrophin-releasing factor 2 receptor antagonist did not alter PYY(3-36) inhibitory action. PYY and PYY(3-36) significantly reduced restraint-stimulated defecation, and PYY(3-36) inhibited high-amplitude distal colonic contractions in restrained conscious mice for 1 h, by intraluminal pressure with the use of a microtransducer. PYY suppression of intraperitoneal 5-hydroxytryptophan induced FPO and diarrhea was blocked by the Y(2) antagonist, BIIE0246, injected intraperitoneally and mimicked by PYY(3-36), but not [Leu(31),Pro(34)]NPY. PYY(3-36) also inhibited bethanechol-stimulated FPO and diarrhea. PYY(3-36) inhibited basal FPO during nocturnal feeding period and light phase in fasted/refed mice for 2-3 h, whereas the reduction of food intake lasted for only 1 h. PYY(3-36) delayed gastric emptying after fasting-refeeding by 48% and distal colonic transit time by 104%, whereas [Leu(31),Pro(34)]NPY had no effect. In the proximal and distal colon, higher Y(2) mRNA expression was detected in the mucosa than in muscle layers, and Y(2) immunoreactivity was located in nerve terminals around myenteric neurons. These data established that PYY/PYY(3-36) potently inhibits basal and stress/serotonin/cholinergic-stimulated propulsive colonic motor function in conscious mice, likely via Y(2) receptors.

Topics: 5-Hydroxytryptophan; Acute Disease; Animals; Arginine; Benzazepines; Bethanechol; Colon; Consciousness; Diarrhea; Eating; Efferent Pathways; Gastric Emptying; Gastrointestinal Motility; Male; Mice; Mice, Inbred C57BL; Myenteric Plexus; Neuropeptide Y; Parasympathomimetics; Peptide Fragments; Peptide YY; Receptors, Neuropeptide Y; Restraint, Physical; Stress, Physiological

Peptide YY (PYY)(3-36), a neuropeptide Y (NPY) Y2 receptor agonist, is a powerful inhibitor of intestinal secretion. Based on this anti-secretory effect, NPY Y2 receptor agonists may be useful as novel anti-diarrheal agents, but anti-diarrheal efficacy has yet to be determined. We therefore examined the anti-diarrheal efficacy of PYY(3-36) and a selective Y2 receptor agonist, N-acetyl-[Leu28, Leu31]-NPY(24-36), in experimental mouse models of diarrhea. Intraperitoneal administration of PYY(3-36) (0.01-1mg/kg) and N-acetyl-[Leu28, Leu31]-NPY(24-36) (10mg/kg) significantly inhibited diarrhea (increase in wet fecal weight and diarrhea score) induced by dimethyl-prostaglandin E2, 5-hydroxytryptamine, and castor oil. Anti-diarrheal activities of PYY(3-36) and N-acetyl-[Leu28, Leu31]-NPY(24-36) were comparable to the effects of loperamide (1mg/kg), a widely used anti-diarrheal drug. To clarify the anti-diarrheal mechanisms of NPY Y2 receptor agonists, we investigated the effects of PYY(3-36) and N-acetyl-[Leu28, Leu31]-NPY(24-36) on intestinal fluid secretion and colonic transit. PYY(3-36) (1mg/kg) and N-acetyl-[Leu28, Leu31]-NPY(24-36) (10mg/kg) significantly reduced dimethyl-prostaglandin E2-induced intestinal fluid accumulation in conscious mice, suggesting that NPY Y2 receptor agonists inhibit diarrhea, at least in part, by reducing intestinal secretion. In addition, PYY(3-36) (0.01-1mg/kg) and N-acetyl-[Leu28, Leu31]-NPY(24-36) (10mg/kg) potently inhibited normal fecal output, suggesting that NPY Y2 receptor activation inhibits colonic motor function and NPY Y2 receptor agonists inhibit diarrhea partly by slowing colonic transit. These results indicate that NPY Y2 receptor agonists inhibit diarrhea in mice by not only reducing intestinal fluid secretion, but also slowing colonic transit, and illustrate the therapeutic potential of NPY Y2 receptor agonists as effective treatments for diarrhea.

Topics: Animals; Antidiarrheals; Diarrhea; Disease Models, Animal; Gastrointestinal Transit; Humans; Intestinal Secretions; Loperamide; Male; Mice; Mice, Inbred C57BL; Peptide Fragments; Peptide YY; Receptors, Neuropeptide Y

To evaluate the effects of diarrhea on appetite among Peruvian children age 12 to 71 months and to assess whether elevated plasma levels of peptide YY, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta contribute to anorexia in this population.. A total of 46 Peruvian children with diarrhea and 46 healthy controls underwent an observed feeding trial that was repeated when cases were healthy. Blood samples were obtained from 30 cases and 30 controls at the first trial and from 30 cases at the second trial and assayed for peptide YY, TNF-alpha, and IL-1beta.. In the cases, mean consumption was less when sick than when healthy. The mean plasma level of peptide YY was higher for cases than controls and higher for cases when sick than when healthy. TNF-alpha levels were higher in cases than controls at visit 1 and also higher in cases when sick than when healthy. There were no differences in IL-1beta levels between cases and controls or between cases when sick and healthy. Peptide YY levels in children with diarrhea correlated with the likelihood of them eating less when sick than when healthy.. Elevated serum peptide YY may be a mechanism for anorexia in children with diarrhea.

Topics: Anorexia; Appetite; Case-Control Studies; Child, Preschool; Diarrhea; Female; Gastrointestinal Hormones; Humans; Infant; Interleukin-1beta; Intestinal Mucosa; Male; Peptide YY; Treatment Outcome; Tumor Necrosis Factor-alpha

Peptide YY (PYY) is produced by endocrine cells in the lower gastrointestinal tract. The main functions of PYY are antisecretory effects in the colon and inhibition of gastrointestinal motility. We chose PYY as an index of the intrinsic factor in diarrhea and examined the influence of changes induced in a diarrhea rat model by administration of 4 types of laxative and loperamide hydrochloride (loperamide) as an agent for the treatment of diarrhea. A specific radioimmunoassay was performed to determine plasma and intestinal mucosal PYY concentrations. PYY in the rat intestinal tissue extract was distributed at a high density in the lower intestinal mucosa. In the diarrhea rat model, multiple changes in PYY concentrations in the intestinal mucosa and plasma were observed. In rats administered castor oil and sodium picosulfate, the intestinal mucosal PYY levels significantly decreased in a dose-dependent manner. Plasma PYY levels significantly decreased only in rats administered magnesium citrate. Next, we examined the influence of loperamide administration on the intestinal mucosa and plasma PYY concentrations in these rats. Loperamide administration resulted in multiple changes in plasma and intestinal mucosa PYY concentrations, along with an improvement in the diarrhea. Our research showed that the endocrine hormone PYY is involved in the onset of diarrhea, the course of the condition, and the manifestation of medicinal effects in the lower intestine.

Topics: Animals; Antidiarrheals; Diarrhea; Disease Models, Animal; Dose-Response Relationship, Drug; Gastrointestinal Motility; Intestinal Mucosa; Loperamide; Peptide YY; Radioimmunoassay; Rats; Rats, Wistar

To assess the levels of gut peptides involved in gastrointestinal motor, secretory and sensory function in colonic biopsies in irritable bowel syndrome (IBS) patients and healthy controls.. We studied 34 patients with IBS and 15 subjects without gastrointestinal symptoms. The predominant bowel pattern in the IBS patients was constipation in 17 patients (IBS-C) and diarrhoea in 17 patients (IBS-D). With radioimmunoassay, the levels of vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and peptide YY (PYY) were analysed in biopsies from the descending colon and ascending colon obtained during colonoscopy.. The IBS patients had lower levels of PYY in the descending colon than the controls, but the levels in the ascending colon did not differ. The NPY levels were lower in IBS-D than in IBS-C, both in the ascending colon and in the descending colon. Low levels of VIP were more common in IBS patients, but mean levels did not differ between groups. No group differences were observed for substance P. The levels of VIP, substance P and NPY were higher in the ascending colon than in the descending colon, whereas the opposite pattern was seen for PYY.. IBS patients demonstrate lower levels of PYY in the descending colon than controls. Colonic NPY levels differ between IBS subgroups based on the predominant bowel pattern. These findings may reflect the pathophysiology of IBS and the symptom variation within the IBS population.

Topics: Adult; Aged; Biopsy; Case-Control Studies; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Female; Humans; Male; Middle Aged; Neuropeptide Y; Peptide YY; Substance P; Vasoactive Intestinal Peptide

The aim of the study was to investigate the effect of ileojejunal transposition, in which the distal ileum is interposed isoperistaltically into the proximal jejunum, on gastric emptying, gastrointestinal motility, and fecal water content in dogs with total colectomy.. Dogs were divided into three groups: dogs with intact colons (control), total colectomy alone (sham operated group), or total colectomy and ileojejunal transposition group. The alimentary tract was reconstructed by ileal J-pouch-rectal anastomosis. Gastric emptying was measured by a validated freeze-drying method, and gastrointestinal motility was measured by strain gauge force transducers. Plasma peptide YY was measured by specific radioimmunoassay. Fecal water content was measured in dogs with total colectomy.. Gastric emptying of solids in the ileojejunal transposition group was delayed longer than 120 minutes after meal ingestion compared with that in the sham operated group. The duration of the digestive state was prolonged in the ileojejunal transposition group, only when compared with the control group. Plasma peptide YY was increased in the ileojejunal transposition group compared with the sham operated group. Fecal water content was decreased in the ileojejunal transposition group compared with the sham operated group.. Ileojejunal transposition delays gastric emptying of solids and decreases fecal water content in dogs with total colectomy, indicating that ileojejunal transposition might be able to improve intractable watery diarrhea after total colectomy.

Topics: Animals; Colectomy; Colon; Diarrhea; Disease Models, Animal; Dogs; Feces; Gastric Emptying; Gastrointestinal Motility; Ileum; Jejunoileal Bypass; Jejunum; Peptide YY; Time Factors

Gastric emptying was measured in female non-obese diabetic (NOD) mice with a duration of diabetes of 28-35 days. As controls, age- and sex-matched BLAB/cJ mice were used. Gastric emptying of diabetic mice was significantly slower than that of controls. The faeces weight and water content were significantly higher in diabetic mice than controls. The endocrine cells known to correlate with gastric emptying, namely secretin, serotonin, peptide YY (PYY) and enteroglucagon cells, were identified by immunocytochemistry and quantified by computer image analysis. The densities of duodenal secretin, serotonin and colonic PYY cells in NOD mice were significantly higher than that of control mice. Changes in these three endocrine cell types may play a role in delayed gastric emptying and in the manifestation of diarrhoea in this animal model of human diabetes type 1.

Topics: Animals; Colon; Diabetes Mellitus, Type 1; Diarrhea; Duodenum; Endocrine Glands; Feces; Female; Gastric Emptying; Mice; Mice, Inbred NOD; Peptide YY; Reference Values; Secretin; Serotonin; Water

Peptide YY is an ileocolonic peptide known to inhibit postprandial and cholecystokinin-induced pancreatic exocrine secretion. It has also been shown to increase intestinal water and electrolyte absorption. These findings implicate PYY as being potentially useful for controlling watery diarrhea. Although its inhibitory effect on stimulated pancreatic secretion has been well established, PYY effects on interdigestive, unstimulated pancreatic secretion is not known. This study was designed to evaluate the effect of PYY on basal pancreatic exocrine secretion in a conscious rat. Male Sprague-Dawley rats were prepared with catheters for internal biliary bypass, pancreatic juice collection, and intraduodenal reinfusion of pancreatic juice. Jugular and carotid catheters were inserted for drug infusions and blood sampling. After overnight recovery, fasting rats were infused over 6 hours with saline or PYY (400 or 800 pmol/kg/hr). Pancreatic juice was measured and sampled at 60-minute intervals for volume and its protein and bicarbonate content. The remainder was reinfused into the duodenum. Before and after the experiment, pancreatic juice was automatically reinfused by a photocell-controlled peristaltic pump system. Intraductal pancreatic secretion was not affected by PYY at a dose of 400 pmol/kg/hr. PYY at a dose of 800 pmol/kg/hr significantly reduced the volume of pancreatic secretion and its protein and bicarbonate content. Pancreatic secretory response normalized within 24 hours. In conclusion, unstimulated pancreatic exocrine secretion can be inhibited by exogenous PYY in the rat.

Topics: Amylases; Animals; Bicarbonates; Body Water; Cholecystokinin; Diarrhea; Digestion; Electrolytes; Gastrointestinal Hormones; Infusion Pumps; Injections, Intravenous; Intestinal Mucosa; Intestines; Male; Pancreatic Juice; Pancreatin; Peptide YY; Peptides; Proteins; Rats; Rats, Sprague-Dawley

To investigate whether peptide YY (PYY) has a role in minimising fluid loss during diarrhoea, its effect on hypersecretion induced by vasoactive intestinal peptide (VIP) was studied in seven subjects with ileostomies. An isotonic electrolyte solution containing polyethylene glycol 4000 was infused directly into the duodenum and the effluent was collected for 40 min (baseline), then VIP was infused intravenously at 5 pmol.kg-1.min-1 for 500 min. PYY was infused intravenously at low doses (0.4 and 0.2 pmol.kg-1.min-1) for 100 min each during the continuous VIP infusion. Small-intestinal secretion was assessed by effluent weight and by polyethylene glycol dilution, which gave similar results. Plateau ileal output was 501 (SEM 33) ml/h during VIP infusion. PYY caused significant falls in secretion--to 404 (48) ml/h for the lower dose and to 323 (75) ml/h for the higher. It also prolonged small-bowel transit. These findings suggest that PYY is a natural inhibitor of diarrhoea and that its therapeutic potential merits investigation.

Topics: Diarrhea; Female; Gastrointestinal Transit; Humans; Ileostomy; Ileum; Infusions, Intravenous; Intestinal Absorption; Male; Middle Aged; Peptide YY; Peptides; Random Allocation; Stimulation, Chemical; Vasoactive Intestinal Peptide

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 responses. These changes in the secretion, may shed light on the physiologic role of this newly discovered peptide and on intestinal adaptation to common digestive disorders.

Topics: Adult; Aged; Celiac Disease; Chromatography, Gel; Colitis, Ulcerative; Colonic Diseases, Functional; Crohn Disease; Diarrhea; Diverticulitis; Duodenal Ulcer; Female; Food; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Intestinal Absorption; Male; Middle Aged; Pancreatitis; Peptide YY; Peptides; Radioimmunoassay