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PubMed1984

Effect of long-term fasting of obese patients on pancreatic exocrine function, gastrointestinal hormones and bicarbonate concentration in plasma.

The CCK- and secretin stimulated pancreatic volume, bicarbonate and enzyme secretion was investigated before and during fasting for 20 days in 12 obese subjects. Pancreatic function tests were performed at the start of the fasting period and on the 10th and 20th day. In an additional and comparable group of 8 obese patients plasma concentrations of cholecystokinin (CCK), gastrin and insulin as well as metabolic parameters (bicarbonate, beta-OH-butyrate and free fatty acids) have been measured before and during total fasting. During three weeks of total fasting the average overweight of the patients undergoing pancreatic function tests was reduced from 49 to 31% (-11.5 +/- 1,5 kg). A significant reduction of volume, bicarbonate, trypsin and amylase secretion occurred already after 10 days of total fasting. After 20 days these parameters were further significantly reduced compared to the 10th day. All mentioned parameters were found at the lower limit of the normal range at the end of the fasting period at 20 days. The only exception being lipase secretion; the decrease of this enzyme was not significant at the 5% level. No significant reduction of basal plasma concentrations could be observed for CCK and gastrin during the course of total fasting. The plasma insulin levels were significantly reduced after 7 days whereas at 10 and 20 days insulin concentration was not significantly lowered compared to day 1. A small but significant decrease in the blood bicarbonate concentration could be observed after 7 days of fasting which remained constant up to the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

PubMed1986

Long-term influence of a wheat-bran supplemented diet on secretion of gastrointestinal hormones and on nutrient absorption in healthy man.

Responses of gastric inhibitory polypeptide (GIP), gastrin and vasoactive intestinal polypeptide (VIP) to a test meal and also nutrient absorption were measured in five healthy men before and after 1, 3 and 7 weeks of daily ingestion of 20 g of wheat bran added to a normal balanced diet. Basal levels of the three hormones were not affected by bran ingestion. Bran ingestion induced a progressive decrease of GIP response to the test meal which became significant after 7 weeks at 30 min (373.9 +/- 71.4 vs 231.1 +/- 47.8 pg/ml, mean +/- s.e.m., P less than 0.05) and at 180 min (389.4 +/- 43.9 vs 262.2 +/- 37.9 pg/ml, P less than 0.01). Gastrin release did not change except for a slight but not significant decrease after 3 weeks. There was no VIP secretion after meal ingestion and addition of bran caused no change. Blood glucose response decreased with time with the greatest effects during the third week with fibre at 30 min (5.00 +/- 0.50 vs 7.38 +/- 0.05 mmol/l before bran), and at 60 min (3.88 +/- 0.34 vs 5.94 +/- 0.27 mmol/l before bran, P less than 0.05). Wet and dry weight of faeces increased by at least 60 per cent from the first week with bran onwards. Faecal nitrogen and fat also increased from 1.77 +/- 0.16 to 2.44 +/- 0.13 g/d for nitrogen (P less than 0.02) and threefold for fat (from 3.78 +/- 0.58 to 10.35 +/- 0.67 per cent dry weight, P less than 0.005) at the third week. Fat and nitrogen contents remained higher until the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1987

Effect of peptide YY on cephalic, gastric, and intestinal phases of gastric acid secretion and on the release of gastrointestinal hormones.

The objective of this study was to investigate the effects of a novel gut peptide, peptide YY (PYY), on the cephalic, gastric, and intestinal phases of gastric acid secretion and to explore the mechanisms involved. The cephalic phase of gastric acid secretion, stimulated by the intravenous injection of 2-deoxyglucose (75 mg/kg), was found to be inhibited by intravenous PYY (100, 200, 400 pmol/kg X h) in a dose-related fashion. Peptide YY (200 and 400 pmol/kg X h) also resulted in a significant dose-dependent inhibition of the gastric phase of acid secretion. On the other hand, PYY (400 pmol/kg X h) failed to affect the intestinal phase of gastric acid output. Serum gastrin levels were increased on infusion of 10% liver extract into stomach, but were unaffected on instillation of liver extract into duodenum. Peptide YY did not inhibit the release of gastrin in either the gastric or intestinal phase studies. Furthermore, PYY had no significant effect on either the basal release of secretin, gastric inhibitory polypeptide, pancreatic polypeptide, or neurotensin, or on the stimulated release of pancreatic polypeptide by 2-deoxyglucose. The specific binding of gastrin to its receptors on the fundic mucosa was also unaffected by PYY. These results indicate that PYY inhibits the cephalic and gastric phases of acid secretion independently, and that its actions are not mediated by either a negative effect on gastrin release or a positive effect on the release of some of the known acid inhibitors, or by an inhibition of gastrin binding to its receptors on the fundic cells. Our present findings (in combination with our previous findings of inhibition of pentagastrin- and bethanechol-stimulated gastric acid secretion by PYY, independent of the vagal cholinergic mechanism) indicate that the action of PYY is either direct on the parietal cells or is mediated by yet another, unidentified, inhibitor.

Animals↗

PubMed2003

Role of gastrointestinal hormones in postprandial reduction of bone resorption.

UNLABELLED: Collagen type I fragments, reflecting bone resorption, and release of gut hormones were investigated after a meal. Investigations led to a dose escalation study with glucagon like peptide-2 (GLP-2) in postmenopausal women. We found a dose-dependent effect of GLP-2 on the reduction of bone resorption. INTRODUCTION: The C-terminal telopeptide region of type I collagen as measured in serum (s-CTX) can be used to assess bone resorption. This marker of bone resorption has a significant circadian variation that is influenced by food intake. However, the mediator of this variation has not been identified. MATERIALS AND METHODS: We studied the release of the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2; a representative of the intestinal proglucagon-derived peptides) after ingestion of glucose, fat, protein, and fructose, as well as their effects after parenteral administration in relation to bone turnover processes in healthy volunteers. Furthermore, we studied the effect on bone turnover of a single subcutaneous injection of GLP-2 in four different dosages (100, 200, 400, or 800 microg GLP-2) or placebo in 60 postmenopausal women (mean age, 61 +/- 5 years). RESULTS: All macronutrients significantly (p < 0.05) reduced bone resorption as assessed by s-CTX (39-52% from baseline), and only the glucagon-like peptides were secreted in parallel. Parenteral administration of GIP and GLP-1 did not result in a reduction of the s-CTX level, whereas GLP-2 caused a statistically significant and dose-dependent reduction in the s-CTX level from baseline compared with placebo (p < 0.05). Urine DPD/creatinine, a marker of bone resorption, was significantly reduced by 25% from baseline in the 800-microg GLP-2 group (p < 0.01). An area under the curve (AUC(0-8h)) analysis for s-CTX after GLP-2 injection confirmed the dose-dependent decrease (ANOVA, p = 0.05). The s-osteocalcin level was unaffected by the GLP-2 treatment. CONCLUSION: These studies exclude both GIP and GLP-1 as key mediators for the immediate reduction in bone resorption seen after a meal. The dose-dependent reduction of bone resorption markers found after subcutaneous injection of GLP-2 warrants further investigation into the mechanism and importance of GLP-2 for the bone turnover processes.

Adult↗

PubMed1989

Plasma gastrointestinal hormones during spontaneous and induced menstrual cycles.

Plasma levels of secretin, vasoactive intestinal polypeptide (VIP), somatostatin (SRIH), motilin, and/or pancreatic polypeptide, as well as serum estradiol, progesterone, PRL, LH, FSH, and/or GH were measured during the follicular phase, midcycle, and luteal phase of a spontaneous menstrual cycle in eight women and during ovarian stimulation with clomiphene citrate/human menopausal gonadotropin and hCG for in vitro fertilization in nine women. Plasma SRIH concentrations were significantly (P less than 0.02) higher in the luteal phase of spontaneous menstrual cycles than in follicular phase and midcycle. Serum GH levels, however, did not change. Plasma motilin concentrations also were higher in the luteal phase than at mid-cycle (P less than 0.04). Plasma secretin, VIP, and pancreatic polypeptide concentrations did not change during the cycle. Throughout the spontaneous menstrual cycle we found significant positive correlations between plasma SRIH and serum progesterone (P less than 0.007; r = 0.5869), plasma motilin and serum progesterone (P less than 0.02; r = 0.5331), plasma secretin and serum estradiol (P less than 0.04; r = 0.4711), and plasma secretin and serum PRL (P less than 0.02; r = 0.5507). During ovarian stimulation both plasma secretin and VIP gradually increased to a peak on cycle days 0 and 1, respectively (day 0 = the day of hCG injection), whereas plasma SRIH did not change. Serum estradiol and PRL increased significantly, and both peaked on cycle day 1. During ovarian stimulation plasma secretin correlated significantly with serum estradiol (P less than 0.00001; r = 0.9333), serum PRL (P less than 0.03; r = 0.6521), and plasma VIP (P less than 0.03; r = 0.6534). In addition, plasma VIP and serum PRL both correlated significantly with serum estradiol (P less than 0.05; r = 0.6024 and P less than 0.04; r = 0.6384, respectively). These results indicate 1) a possible effect of progesterone on the release of SRIH and motilin during the spontaneous menstrual cycle; 2) the unaltered serum GH concentrations in the luteal phase of the spontaneous menstrual cycle despite elevated plasma SRIH levels are probably due to a stimulatory effect of both progesterone and motilin on GH release; and 3) the increase in plasma secretin and VIP concentrations during ovarian stimulation is probably secondary to the concomitant increase in serum estradiol and/or PRL. We suggest that estradiol and/or PRL beyond a certain threshold level stimulate the release of secretin, and possibly also VIP, into plasma.

Adult↗

PubMed1997

Gastrointestinal hormones and gastric emptying 20 years after jejunoileal bypass for massive obesity.

OBJECTIVE: Some studies have shown a more rapid gastric emptying in obese subjects. Six to twelve months after jejunoileal bypass (JIB) neurotensin (NT) and enteroglucagon have been shown to be elevated after food intake. These hormones, together with peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) have been implicated in the reduction of upper gastrointestinal motility seen after infusion of nutrients into the ileum. AIM: To study if the postprandial gut hormone pattern and gastric emptying is altered 20 y after JIB. SUBJECTS: Seven subjects operated with JIB a mean (s.d.) 20 +/- 3 y ago, with a BMI of 44 +/- 4 kg/m2 at the time of surgery and 31 +/- 4 at present. For comparison seven sex-matched non-operated obese controls (BMI 43 +/- 3) were studied. METHODS: Serial blood samples were obtained every 10 min after intake of a 280 kcal meal. Radioimmunoassays for motilin, cholecystokinin (CCK), NT, PYY and GLP-1 were performed. Gastric emptying of a solid meal was studied using a radioactively labelled omelette (of 310 kcal) for 120 min). RESULTS: After JIB postprandial motilin, CCK, NT, PYY and GLP-1 were elevated compared to non-operated obese subjects. Similarly, basal levels of CCK, motilin, GLP-1 and PYY were elevated in the operated group. No difference was observed in the rate of gastric emptying between the two groups. CONCLUSION: Both fasting and postprandial gut hormone levels are elevated 20 y after JIB. The impact of long-term rapid stimulation of the ileum and subsequent raised gut hormone levels on gastric emptying is not clear.

Cholecystokinin↗

PubMed1999

Quality of life, nutritional status and gastrointestinal hormone profile following the Whipple procedure.

Pancreatic cancer is the second commonest gastrointestinal cancer, after colorectal cancer, in Canada, and most other European and North American countries. Unfortunately, most patients present with advanced locoregional or metastatic disease. For the 10-20% of patients who have localized disease, pancreatic resection is generally the preferred treatment option. Because pancreaticoduodenectomy can be performed safely in expert hands, it has become a more accepted procedure for patients with pancreatic cancer. Furthermore, it has also meant that there is increasing scrutiny of the longterm outcome of patients, especially their nutritional status and quality of life. In a study of 25 unselected patients who had a Whipple procedure at least 6 months previously and were not known to have residual or recurrent disease, patients appeared to have few gastrointestinal symptoms compared to control patients. However, none of the subjects appeared to be clinically malnourished. Dietary intake and lean body mass were comparable to that of the control group. Quality of life was excellent in these patients. The mean utilities were 0.98 and 1.0 suggesting near normal wellbeing. Similarly, results using the SIP and GIQLI suggested no/minimal impairment in general wellbeing and gastrointestinal function. Two other studies suggest that median survival and performance status are improved in patients having a resection, but it may be due to their disease being more favorable rather than the treatment being beneficial. Further studies objectively assessing the quality of life of all patients undergoing treatment for pancreatic cancer at the various disease stages are required.

Humans↗

PubMed2000

Stimulated gastrointestinal hormone release and gallbladder contraction during continuous jejunal feeding in patients with pancreatic pseudocyst is inhibited by octreotide.

BACKGROUND: Continuous enteral feeding, the old-new therapeutic modality in the treatment of patients with acute pancreatitis and those with complications is considered to bypass the cephalic, the gastric, and (at least in part) the intestinal phase of pancreatic secretion. The aim of this study was to test the GI hormonal changes and gallbladder motility during CJF in patients with pancreatic pseudocysts following acute pancreatitis, with or without octreotide pretreatment. PATIENTS AND METHODS: In 15 patients with pancreatic pseudocysts, an 8-French (8F) nasojejunal catheter was positioned into the jejunum distal to the ligament of Treitz during duodenoscopy. On test d 1, blood samples were taken for CCK, gastrin, insulin-like immunoreactivity (IRI), glucagon, and glucose measurements prior to and at 20, 40, 60, and 120 min following jejunal saline infusion at a rate of 2 mL/min. The gallbladder volumes were determined simultaneously by ultrasonography. On test d 2, CJF (175 kcal/h) was started by the same route and at the same infusion rate. Analogous measurements were performed as indicated above. On test d 3, 100 microg of octreotide was administered subcutaneously and the previous procedure was repeated. The plasma level of CCK and glucagon and the serum levels of IRI and gastrin were determined by bioassay and radioimmunoassay (RIA), respectively. RESULTS: Significant changes in hormone levels were not observed during jejunal saline perfusion. However, the levels of CCK (5.7+/-0.9 pmol), gastrin (10.6+/-1.3 pmol/L), IRI (27.2+/-5.8 microIU/mL), glucagon (322.8+/-32.4 pg/mL), and glucose (5.8+/-1.0 mmol/L) were significantly increased at 20 min during CJF vs the saline controls (2.0+/-0.3 pmol, 6.8+/-1.1 pmol/L, 7.8+/-0.4 microIU/mL, 172.8+/-33.4 pg/mL, and 4.5+/-0.5 mmol/L, respectively) and remained elevated at 40, 60, and 120 min. Octreotide pretreatment eliminated the increases in CCK, gastrin, IRI, and glucagon levels observed during CJF alone. The significant decrease in gallbladder volume during CJF was also prevented by octreotide pretreatment. CONCLUSION: Continuous jejunal feeding (CJF) elicited significant increases in gastrointestinal (GI) regulatory hormone (cholecystokinin [CCK], gastrin, IRI, and glucagon) levels and evoked a consecutive gallbladder contraction. These biological responses are eliminated by octreotide pretreatment. Further clinical studies are needed to assess the eventual therapeutic effect of octreotide during CJF in patients with pancreatic pseudocyst.

Adult↗

PubMed2005

Gastrointestinal hormones and food intake.

Despite dramatic fluctuations in calorie intake, animals maintain a very stable body weight. The reason is that energy intake and expenditure are precisely matched. Long-term regulation of energy balance is dependent on the coordination and interpretation of signals such as those given by insulin and leptin indicating sufficient long-term energy stores as well as short-term, meal-related signals such as those given by cholecystokinin (CCK). Within the last 30 years, our knowledge of short-term signals has increased dramatically. Throughout the cephalo-caudal axis of the gastrointestinal system, discrete enteroendocrine cells respond to both mechanical and chemical stimulation. Meal-associated hormone release is dependent on the concentration and composition of the nutrients ingested. Released signals are transmitted neurally through vagal afferents or humorally as circulating ligands for specific receptor populations in the periphery and central nervous system. These signals are interpreted by the CNS and manifested as a behavioral modification of feeding. This review will present past and recent literature in support of gut hormones and their roles as mediators of satiety. Evidence from pharmacologic and physiologic studies involving both humans and rodents will be presented, along with a short section outlining the knowledge gained through the use of murine knockout models. Last, the contribution of satiety hormones as likely mediators of the effectiveness seen following obesity surgery will be reviewed. Although traditionally thought of as short-term, meal-related signals, enhanced, chronic hormone secretion and signaling resulting from gut reconstruction as seen with gastric bypass surgery most likely contributes to the superior efficacy of surgery as a treatment for obesity.

Animals↗

PubMed1984

Gastrointestinal hormones in birds: morphological, chemical, and developmental aspects.

Historically, the enterochromaffin cell was the first endocrine cell type detected in avian gut; subsequently, a number of types of such cells were distinguished on the basis of the ultrastructural features of the secretory granules. More recently, immunocytochemical procedures have revealed somatostatin-, pancreatic polypeptide (PP)-, polypeptide YY-, glucagon-, secretin-, vasoactive intestinal peptide (VIP)-, gastrin-, cholecystokinin-, neurotensin-, bombesin-, substance P-, enkephalin-, motilin-, and FMRFamide-like immunoreactivity in avian gastrointestinal endocrine cells. Most endocrine cells are located in the antrum; there are a number in the proventriculus and small intestine but few in the gizzard, cecum, and rectum. Several avian gastroenteropancreatic hormones, including glucagon, VIP, secretin, bombesin, neurotensin, and PP, have been isolated and sequenced. They resemble the equivalent mammalian peptides in terms of molecular size but differ in amino acid composition and sequence; some (e.g., VIP) differ only in minor respects, others (e.g., secretin) more radically. Gastrointestinal endocrine cells appear late in development; available data indicate that few types are recognized by either immunocytochemistry or electron microscopy before 16 days of incubation. Experimental evidence has shown that at least the majority of gut endocrine cells are of endodermal origin and are not derived from the neural crest or neuroectoderm as earlier proposed. In early embryos, the progenitors of gastrointestinal endocrine cells are more widespread than are the differentiated cells in chicks at hatching. This, along with other observations, raises the question of factors that might influence the differentiation of gut endocrine cells.

APUD Cells↗

PubMedDate not supplied

Intestinal, pancreatic, and hepatic effects of gastrointestinal hormones in a total parenteral nutrition rat model.

The adverse effects of long-term total parenteral nutrition (TPN) are well documented. Lack of gastrointestinal (GI) stimulation from oral feeding, reduction of GI hormone secretion, and interruption of enterohepatic circulation of bile may be found. TPN results in atrophy of the digestive system, intestinal bacterial overgrowth and translocation, liver cell damage, and gallstone formation. In addition, the increase incidence of sepsis of gut origin may lead to an increase in mortality. In some studies, results of the administration of GI hormones to patients receiving prolonged TPN suggest the possibility of reducing some of the adverse effects of long-term TPN. To evaluate the role of GI hormone in the prevention of adverse effects of TPN, we designed the following study: 50 young adult male Wistar rats, weighing approximately 200 g, were divided into five equal groups. All animals received identical TPN infusate for 7 days. GI hormone was added to the TPN infusate as follows: Group A (control) received no GI hormone, group B was given glucagon at a dosage of 330 micrograms/kg per day, group C was administered cholecystokinin 2 Ivy dog units twice a day, group D received secretin 2 clinical units twice a day, and group E was given both cholecystokinin and secretin at the dosages stated for groups C and D. Maintenance of mucosal brush-border hydrolase activity was found in group B. Neither atrophy of the pancreas nor hypoplasia of intestinal villi was observed in groups C and D. Group C showed improvement of liver function-associated tests, better weight gain, and acceleration of enterohepatic circulation of bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1970