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PubMed1992

Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-1-diabetic patients after successful combined pancreas and kidney transplantation.

The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1-diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas-kidney-transplanted patients (by 88%; P = 0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and - to a lesser degree - also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P = 0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P = 0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas-kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Hormonal regulation of key gluconeogenic enzymes and glucose release in cultured hepatocytes: effects of dexamethasone and gastrointestinal hormones on glucagon action.

Hormonal regulation of key gluconeogenic enzymes and glucose release by glucagon, dexamethasone, secretin and somatostatin was evaluated in maintenance cultured rat hepatocytes. (i) Phosphoenolpyruvate (PEP)-carboxykinase activity declined rapidly during the first 24 h in serum- and hormone-free culture with a further slight decay during the following 2 days. Dexamethasone and glucagon independently increased PEP-carboxykinase and acted synergistically when added in combination. Glucose-6-phosphatase activity declining linearly during hormone-free culture was stimulated by glucagon. Dexamethasone itself was without significant effects but completely abolished glucagon action. Fructose-1,6-diphosphatase was maintained at its initial level during the first day under control conditions and declined thereafter. Neither glucagon nor dexamethasone affected total activity or substrate (fructose-1,6-diphosphate) affinity of this enzyme. In short-term experiments on cells cultured under control conditions, protein synthesis-dependent stimulation of PEP-carboxykinase by glucagon and the permissive action of dexamethasone was demonstrated. Glucose-6-phosphatase and fructose-1,6-diphosphatase were not altered by hormones within this period. (ii) Stimulation by glucagon of gluconeogenesis was independent of its action on PEP-carboxykinase. Dexamethasone inhibited glycogenolysis but maintained glucose release at control levels probably by stimulation of gluconeogenesis. When added in combination, the glycogen-preserving action of dexamethasone acutely reduced the glucose release in response to glucagon. Glucagon sensitivity remained unchanged. (iii) The gastrointestinal hormones secretin and somatostatin were ineffective in modulating basal or glucagon-stimulated glucose release and gluconeogenic key enzymes. They are therefore unlikely to play a physiological role in hepatic glucose metabolism.

Animals↗

PubMed1976

[Gastrointestinal hormones and blood circulation in the gastric mucosa].

The gastrointestinal hormones influence gastric mucosal blood flow in different ways. Gastrin, secretin and pancreocymin increase gastric mucosal blood flow, glucagon, vip and somatostatin decrease it. Motilin has a special position. Given alone motilin improves gastric mucosal blood flow, wheras it reduces gastric mucosal blood flow after previous administration of pentagastrin or histamin.

Cholecystokinin↗

PubMed1995

Postprandial mesenteric blood flow in humans: relationship to endogenous gastrointestinal hormone secretion and energy content of food.

OBJECTIVE: To examine the relationship between postprandial superior mesenteric arterial blood flow (SMABF) and endogenous gastrointestinal hormone secretion after liquid meals of varying energy content. METHODS: Six healthy volunteers received four isovolumetric meals of differing energy content. SMABF was measured before and for 120 min after feeding using duplex ultrasound; plasma levels of gastrointestinal hormones and noradrenaline were measured. RESULTS: Results are given as means +/- SEM. Postprandial SMABF increased after each meal; the peak mean percentage increment occurred at 28 +/- 8 min, varying from 106 +/- 26% (P < 0.05) with the 800 kj meal to 240 +/- 62% (P < 0.05) with the 4800 kj meal. The rise was sustained and correlated with energy content (r = 0.969; P = 0.031). The subjects' pulse rate increased after each meal and the increment appeared to be related to meal size (r = 0.990; P = 0.008). Blood pressure did not change. The postprandial concentration of N-terminal neurotensin peaked between 30 and 120 min. The mean peak concentration increased from a baseline value of 30.9 +/- 3.5 ng/l by 19.3 ng/l after 800 kj, 31 ng/l after 1600 kj, 38 ng/l after 2400 kj and 64.3 ng/l after the 4800 kj meal (all differences P < 0.05). The rise was sustained and correlated with energy content (r = 0.967; P = 0.033). Plasma noradrenaline concentration also increased significantly after each meal and was related to energy content (r = 0.90; P = 0.036). Plasma insulin concentration showed a similar postprandial response but had no relationship to energy content. Gastrin concentration increased transiently but changes in the concentration of glucagon, vasoactive intestinal polypeptide and neurokinin A were not significant. CONCLUSIONS: The results indicate a relationship between meal energy content, postprandial SMABF and pulse rate increments. Postprandial increases in N-terminal neurotensin and noradrenaline concentration were also related to energy content and may indicate a role for these hormones in the control of SMABF after feeding.

Adult↗

PubMed2006

Postprandial gastrointestinal hormone production is different, depending on the type of reconstruction following total gastrectomy.

OBJECTIVES: The present study examines the differences in gastrointestinal hormone production at 3 different reconstruction types after total gastrectomy. BACKGROUND DATA: Total gastrectomy causes significant weight loss, mainly due to a reduced caloric intake probably because of a lack of initiative to eat or early satiety during meals. Behind this phenomenon a disturbed gastrointestinal hormone production can be presumed. METHODS: Patients participating in a randomized study were recruited for the clinical experiment. Seven patients with simple Roux-en-Y reconstruction, 11 with aboral pouch (AP) construction, and 10 with aboral pouch with preserved duodenal passage (APwPDP) reconstruction, as well as 6 healthy volunteers were examined. Blood samples were taken 5 minutes before and 15, 30, and 60 minutes after ingestion of a liquid test meal. Plasma concentrations for insulin, cholecystokinin, and somatostatin were determined by radioimmunoassay analysis. RESULTS: Postprandial hyperglycemia was observed in patients after total gastrectomy most prominently in groups with duodenal exclusion (Roux-en-Y and AP) compared with healthy controls. Postprandial insulin curves reached significantly higher levels in all operated groups compared with controls, however, with no difference according to reconstruction type. Significantly higher cholecystokinin levels and higher integrated production of cholecystokinin were observed in Roux-en-Y and AP groups compared with APwPDP and control. Postprandial somatostatin levels were significantly different between the 4 groups, and highest levels and integrated secretions were reached in AP group, lowest in APwPDP and normal groups. CONCLUSION: A disturbed glucose homeostasis was observed in gastrectomized patients most prominently in the Roux-en-Y group. Also, cholecystokinin and somatostatin response differed significantly in favor of duodenal passage preservation after total gastrectomy. Cholecystokinin levels close to physiologic found at APwPDP reconstruction may contribute to a physiologic satiation in reconstructions with preserved duodenal passage after total gastrectomy.

Anastomosis, Roux-en-Y↗

PubMed2002

[Regulation of the functional status of the lower esophageal sphincter with gastrointestinal hormones in cardiospasm and reflux esophagitis].

A role of gastrointestinal hormones in the regulation of the lower esophageal sphincter was studied in 22 patients with cardiospasm and 21 with reflux esophagitis. The levels of gastrin, vasoactive intestinal polypeptide (VIP), glucagon, insulin, and c peptide were determined by radioactive assay before and after surgical treatment. In opposite abnormalities (cardiospasm and reflux esophagitis), there is a different degree of VIP secretion both at the beginning and after functional exercises. Before and after functional exercises, the level of VIP was higher than in those with cardiospasm. The value of VIP on fasting and after functional exercises may be an additional information to establish the diagnoses of cardiospasm and reflux esophagitis and to evaluate the efficiency of the treatment performed.

Esophageal Achalasia↗

PubMed1980

The effect of metformin treatment on gastric acid secretion and gastrointestinal hormone levels in normal subjects.

Gastric acid secretion and gastrointestinal hormone levels were measured in healthy non-diabetic subjects after metformin treatment (1.5 g/day). The maximum acid output was increased from 15.7 +/- 3.9 mmol/h (mean +/- SEM) to 30.0 +/- 7.1 mmol/h (p < 0.05) and the peak acid output was increased from 16.4 +/- 4.1 mmol/h to 31.7 +/- 7.2 mmol/h (p < 0.05) after two weeks treatment. Serum insulin, gastric inhibitory polypeptide and secretin levels were normal. After treatment for one week, however, there was a significant increase in fasting vasoactive intestinal peptide (VIP) from 83 +/- 6 ng/1 to 102 +/- 9 ng/1 (p < 0.02) and in stimulated VIP from 58 +/- 5 ng/1 to 79 +/- 5 ng/1 (p < 0.05). Stimulated glucagon-like immunoreactivity (GLI) was also increased from 82 +/- 10 ng/1 to 174 +/- 24 ng/1 (p < 0.01) after one week's treatment. It is suggested that metformin acts as a weak histamine agonist.

Adult↗

PubMed1978

Effect of gastrointestinal hormones on isolated bovine parathyroid cells.

The effects of gastrointestinal hormones on cAMP accumulation and parathyroid hormone (PTH) release were investigated in dispersed bovine parathyroid cells. Secretin (10 (-7) M) caused a 4- to 6-fold increase in cAMP accumulation, while glucagon, vasoactive intestinal peptide, and gastrin caused little if any stimulation. Cholecystokinin caused a 2- to 3-fold increase in cAMP accumulation at 10(-6) M, but this effect may be related to contamination with endogenous secretin since synthetic cholecystokinin octapeptide had no effect. Maximal intracellular cAMP accumulation due to 10(-7) M secretin was reached within 5 min and returned to control over the next 30-60 min, concomitant with a progressive rise in extracellular cyclic nucleotide. cAMP accumulation was half-maximally stimulated by 5 x 10(-9) to 1 x 10(-8) M secretin and was unaffected by alpha- or beta-adrenergic or dopaminergic blockers. Parallel effects were noted on PTH release : 10(-8) M secretin caused a 20-50% increment in PTH release at 15 min which persisted for up to 2 h; PTH release was stimulated half-maximally by approximately 6--8 x 10(-9) m secretin. The specificity of the observed results for secretin and the lack of effect of adrenergic antagonists suggest the presence of a receptor for secretin on dispersed bovine parathyroid cells. These results also suggest the possibility that secretin may modulate parathyroid function in vivo in the cow.

Animals↗

PubMed1997

[Anders Jahres PRIZE 1996. Current biological and clinical aspects of gastrointestinal hormones].

1996, the great Jahre Prize for medical research was shared by Professor Jens F Rehfeld of Copenhagen and Professor Mårten Wikström of Helsinki. Jens Rehfeld is one of the world's leading experts on peptide hormones and neuropeptides, and his research has contributed much to our understanding of diseases of the gastrointestinal tract and central nervous system. So many gastrointestinal hormones have now been recognised, that the alimentary canal is considered to constitute the body's largest endocrine organ. Moreover, many hormones occur in several molecular forms and are also synthesised as neurotransmitters in the brain and the peripheral nervous system, and both in classic endocrine cells and cells of the common mucosa. Finally, a number of common tumours also synthesise intestinal peptides that function as growth factors. Gastrointestinal hormones should therefore be interpreted as being intercellular regulators, that are possibly more crucially involved in cancer, diabetes and neuropsychological diseases than in disorders of gastrointestinal secretion and motility.

Awards and Prizes↗

PubMed1990

[The field of endocrinology-gastrointestinal hormones: radioimmunoassay and regulation of plasma levels].

Radioimmunoassay is still by far the most reliable tool for the measurement of plasma gastrointestinal hormones. However, various factors in plasma, without proper control, can give rise to erroneous results in radioimmunoassay. It contains 1) proteolytic enzymes which degradation the peptide 2) plasma nonspecific interference 3) cross reaction of various peptides of similar structure 4) molecular species which the antibody recognizes, and so on. We reviewed the mechanism of increase in plasma levels of pancreatic polypeptide (PP) measured by radioimmunoassay. Its secretion in the basal state as well as after meals in normal humans and dogs is governed mainly by vagal cholinergic mechanism. However, bile acid and other gastrointestinal hormones (Insulin and CCK) play a part in the postprandial PP response in experimentally induced diabetic and total biliary diversion dogs. The production of hydrochloric acid or secretin is not requisite for plasma PP response to an ingested meal.

Animals↗

PubMedDate not supplied

[Gastrointestinal hormones].

Recently, knowledge about the physiological and physiopathological role of some already known gastrointestinal hormones has been increased. At the same time, new biologically active substances (peptides) have been isolated from the gastrointestinal tract and pancreas. Some hormones that were thought to be restricted to the digestive system have been identified in the brain and some peptides localized in the nervous terminals in the myenteric plexuses, actively participate in the biological process of the gut. These findings have made the comprehension of this field more complicated. As a consequence of this, the term of "gastrointestinal endocrinology" is emerging. In this article we will discuss some general concepts of gastrointestinal and pancreatic hormonal physio-pathology and individually, about the role of some hormones and peptides in the normal and abnormal biological process. We emphasize the importance of biochemical diagnosis of those abnormalities.

Gastrointestinal Hormones↗

PubMed1988

[Pathophysiology following biliary reconstruction procedures, with special reference to gastric acid secretion, peptic ulcer, metabolism of carbohydrate and fat, and gastrointestinal hormone release].

Pathophysiological effects following biliary tract reconstruction for benign biliary diseases were investigated from the standpoint of gastric acid secretion, metabolism of nutrients and gastrointestinal hormone release. Patients undergoing Roux-Y hepaticojejunostomy showed a significant increase in maximum acid output at follow-up, although only one case of peptic ulcer was observed. In addition, the frequency of cases showing gastric acid hypersecretion was higher than for jejunal interposition hepaticoduodenostomy. Two kinds of test meals (carbohydrate-rich or fat-rich) were given, on different days, to each patient before and about four weeks after surgery. Plasma concentrations of gastrointestinal hormones and glucose or triglyceride were determined. Fasting concentrations of gut hormones (gastrin, GIP, insulin and GLI) were similar to those before surgery, and increased after the ingestion of the test meals. Gastrin and total GLI levels tended to be higher in the Roux-Y than in the interposition group, and vice versa for both insulin and GIP. The changes in plasma glucose and triglyceride, following the Roux-Y procedure, suggest disturbances in carbohydrate tolerance, fat digestion, and in the anabolic phase of absorbed fat. Patients undergoing the Roux-Y procedure should be carefully followed up, since gastric acid hypersecretion induced by a postprandial augmented release of gastrin was observed.

Adult↗

PubMed1982

Structural similarities among gastrointestinal hormones and related active peptides.

The amino acid sequences of gastrointestinal hormones were compared in fragments of variable spans. Similarities within each of three peptide groups are extensive, but non-unique alignments were also noticed in the glucagon group. Use of different spans demonstrated that structural similarities are unevenly distributed in the gastrin family. Correct phasing was detected even for proteins with few identities and multi-shifted alignments (alcohol dehydrogenases). Tests for alignments among different groups of peptides revealed similarities between bombesin and glucagon or secretin, as well as between caerulein and litorin. Recently determined extended structures suggested the presence of a few deletions/insertions close to the middle of the molecules (two such positions missing in the gastrin-releasing peptide in relation to glucagon). The alignments appear to structurally link large groups of peptide hormones and active peptides. Similarities concentrate in the C-terminal parts, and gaps in the middle. These facts are consistent with known correlations with bioactivities. They also suggest the possibility of evolutionary connections among different peptides as well as corresponding relationships among their receptors.

Amino Acid Sequence↗

PubMed1983

Adenylate cyclase in gastric mucosal biopsies from patients with achlorhydria. Stimulation by PGE2, histamine and gastrointestinal hormones.

Activation of adenylate cyclase (AC) by PGE2, histamine and gastrointestinal hormones was studied in parietal cell-free gastric biopsy specimens from the corpus of patients with proven high gastrin achlorhydria. PGE2, somatostatin, VIP, pentagastrin and secretin activated AC in a concentration-dependent manner both in normal and in atrophic mucosa. Histamine activated AC only in normal gastric mucosa, being entirely ineffective in mucosa devoid of parietal cells. The results indicate that histamine-sensitive AC disappears in patients with achlorhydria, probably due to their loss of parietal cells. Enzyme activity in response to somatostatin, VIP, pentagastrin, secretin and PGE2 remains unchanged in these patients indicating AC localization in nonparietal cells, e.g. chief or mucous cells.

Achlorhydria↗

PubMed2003

Gastrointestinal hormone secretion after surgery in neonates with congenital intestinal anomalies during starvation and introduction of enteral nutrition.

BACKGROUND/PURPOSE: Gastrointestinal hormones modulate gut function in response to enteral nutrition. Infants with a congenital intestinal anomaly with loss of bowel length either pre-or postnatal, who are on total parenteral nutrition for prolonged periods after surgery, are especially prone to a disturbed secretion of gut hormones. The aim of this study was to determine whether circulating gut hormones were altered in these patients and to collect baseline data for future studies in short bowel patients using different enteral substrates. METHODS: Gastrin, cholecystokinin, and peptide YY were measured in 14 operated neonates who had a congenital intestinal anomaly during starvation and introduction of enteral nutrition. None of the neonates had a short bowel. Fourteen neonates who underwent surgery for other major congenital anomalies served as age-matched controls. Gut hormones were measured with radioimmunoassays. RESULTS: Postprandial gut hormone values were higher than basal gut hormone values within both groups. Compared with the controls, postprandial gastrin and cholecystokinin were significantly higher in the patients. CONCLUSIONS: Neonates with a congenital intestinal anomaly in the absence of a short bowel have a similar secretion pattern of gastrointestinal hormones as neonates with a structurally normal intestinal tract, both during starvation and enteral nutrition.

Anastomosis, Surgical↗

PubMed1976

The structure of gastrointestinal hormones.

The primary and secondary structure of the three kinds of gastrointestinal hormones, i.e. gastrin, cholecystokinin-pancreozymin and secretin are discussed.

Amino Acid Sequence↗

PubMed1989

[Gastrointestinal hormones--clinical significance].

The author gives an account of clinical syndromes which develop as a result of overproduction of gastrointestinal hormones. From the various diagnostic approaches, which are not always available or are expensive, the author summarizes the importance of thin-needle biopsy under sonographic control, the argentaffine technique (Grimelius) and histoenzymatic examination for neuron specific enolase. In addition to surgical treatment treatment with streptozotocine, 5-FU, dimethyl triazenoimidazole carboxamide and somatostatin is possible. The author draws attention to the possibility of using somatostatin not only in the treatment of apudomas but also of haemorrhage into the gastrointestinal tract and in the treatment of fistulae. Neuroendocrine factors probably play a significant role in the pathophysiology of irritable colon, Crohn's disease, achalasia and Hirschsprung's disease.

Gastrointestinal Diseases↗

PubMed2005

Dose-related effects of lauric acid on antropyloroduodenal motility, gastrointestinal hormone release, appetite, and energy intake in healthy men.

We recently reported that intraduodenal infusion of lauric acid (C12) (0.375 kcal/min, 106 mM) stimulates isolated pyloric pressure waves (IPPWs), inhibits antral and duodenal pressure waves (PWs), stimulates release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), and suppresses energy intake and that these effects are much greater than those seen in response to isocaloric decanoic acid (C10) infusion. Administration of C12 was, however, associated with nausea, confounding interpretation of the results. The aim of this study was to evaluate the effects of different intraduodenal doses of C12 on antropyloroduodenal (APD) motility, plasma CCK and GLP-1 concentrations, appetite, and energy intake. Thirteen healthy males were studied on 4 days in double-blind, randomized fashion. APD pressures, plasma CCK and GLP-1 concentrations, and appetite perceptions were measured during 90-min ID infusion of C12 at 0.1 (14 mM), 0.2 (28 mM), or 0.4 (56 mM) kcal/min or saline (control; rate 4 ml/min). Energy intake was determined at a buffet meal immediately following infusion. C12 dose-dependently stimulated IPPWs, decreased antral and duodenal motility, and stimulated secretion of CCK and GLP-1 (r > 0.4, P < 0.05 for all). C12 (0.4 kcal/min) suppressed energy intake compared with control, C12 (0.1 kcal/min), and C12 (0.2 kcal/min) (P < 0.05). These effects were observed in the absence of nausea. In conclusion, intraduodenal C12 dose-dependently modulated APD motility and gastrointestinal hormone release in healthy male subjects, whereas effects on energy intake were only apparent with the highest dose infused (0.4 kcal/min), possibly because only at this dose was modulation of APD motility and gastrointestinal hormone secretion sufficient for a suppressant effect on energy intake.

Adult↗