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[Hormonal and pharmacological modification of the ileocecal sphincter].

Ileocecal shincter (ICS) pressure was evaluated in response to hormonal and pharmacological stimuli in rabbits. The effect of exogeneous gastrin (pentagastrin) and glucagon, metoclopramide and neostigmin on the ICS pressure was studied. Gastrin, glucagon and metoclopramide increased the pressure whereas neostigmin lowered it. These results suggest that this junctional zone is not only a valve but a real shincter, which is affected by gastrointestinal hormones and pharmacological substances. Further examinations are necessary to study the role of the ICS after gastrointestinal surgery.

Animals↗

Somatostatin: a historical perspective.

Following the discovery and biochemical characterization of natural somatostatin its action profile has been thoroughly investigated. Although the name somatostatin was coined in virtue of its growth hormone release-inhibiting properties, a number of central and peripheral endocrine and paracrine actions have been ascribed to this peptide. Its inhibitory effect on a series of pituitary and gastrointestinal hormones has characterized somatostatin as a classical brain-gut hormone. Circulating and tissue levels of somatostatin and its possible physiological role are analyzed and clinical implications are drawn.

Animals↗

Effect of hyperglycemia on gastrointestinal and gallbladder motility.

Gastrointestinal motor abnormalities occur frequently in patients with diabetes mellitus. The gastrointestinal motor dysfunction in these patients has been associated with the presence of autonomic neuropathy. Recently, however, several studies have shown that the gastrointestinal motor responses to various stimuli are impaired during acute hyperglycemia in both healthy subjects and diabetic patients. It has been demonstrated that acute hyperglycemia impairs esophageal peristalsis, reduces the lower esophageal sphincter pressure, delays gastric emptying, slows intestinal transit, and reduces the gallbladder contraction in response to various stimuli in healthy subjects. In diabetic patients gastric emptying and gallbladder contraction have been shown to be impaired during hyperglycemia. With regard to the mechanisms of action, it has been suggested that hyperglycemia may affect gastrointestinal function through vagal-cholinergic inhibition, by alterations in serum osmolality, or perhaps by alterations in gastrointestinal hormone secretion.

Diabetes Mellitus↗

Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors.

Ghrelin is a novel gastrointestinal hormone produced by rat and human gastric X-like neuroendocrine cells, which strongly stimulates GH secretion and influences energy balance, gastric motility, and acid secretion. Ghrelin is expressed in pituitary and gastrointestinal endocrine tumors. It binds to the GH secretagogue receptor (GHS-R), which is present in a wide variety of central and peripheral human tissues. The aim of the present study was 2-fold: 1) to determine, by immunohistochemistry and mRNA analysis, whether pancreatic islet cells produce ghrelin and express GHS-R; and 2) to investigate ghrelin and GHS-R expression in pancreatic endocrine tumors. Seven cases of nonneoplastic pancreatic tissue and 28 endocrine tumors were studied. In pancreatic islets, ghrelin immunoreactivity was present in all cases and confined to beta-cells. Eleven of the 28 (39%) endocrine tumors were immunoreactive for ghrelin. In situ hybridization and RT-PCR confirmed the immunohistochemical data for both tumors and islets but also revealed ghrelin mRNA in 8 and 11 additional tumors, respectively. GHS-R 1a and 1b mRNAs were present in 7 of 28 and 14 of 28 tumors, respectively, studied by RT-PCR. These findings demonstrate that ghrelin production is not restricted to the stomach but is also present in pancreatic beta-cells and endocrine tumors (regardless of the type of pancreatic hormone produced, if any). Expression of GHS-R in some of the endocrine tumors studied indicates that autocrine/paracrine circuits may be active in neoplastic conditions.

Adult↗

Development of digestive functions in the newborn ruminant.

To assess the progress of developing digestive functions accurately, it is necessary to evaluate the relative changes of certain variables. Observations have been reported on anatomical, biochemical and physiological changes that occur during the digestive adaptation of the neonatal lamb or calf to the extra-uterine life. For example, chymosin, a milk-clotting acid protease, is maintained by the milk diet at a high level until weaning in calves, as a result of the stimulation by casein of the rate of chymosin synthesis.

Action Potentials↗

[Motor and endocrine function disturbances of the gastrointestinal tract in patients with chronic renal failure (CRF)].

In the chronic renal failure (CRF) there are several upper gastrointestinal symptoms, which result from both disturbed motor function (associated with the delayed gastric emptying) and myoelectrical one (associated with abnormal electrogastrography registration). In patients suffering from CRF, disturbances of the endocrine digestive system function were also demonstrated, which are related to the observations of many gastrointestinal hormones increased levels.

Animals↗

The gastrocolic response: evidence for a neural mechanism.

The aim of this study is to determine the effect of anticholinergic therapy on the gastrocolonic response to a standard meal or its major constituent fat. A rapid increase in rectosigmoidal spike activity occurs after ingesting the standard meal or the fat meal (P less than 0.01). Distal colonic motility returns to fasting levels 50 min after both meals. There is no further increase in spike activity after the 1000-calorie meal, but spike activity increases again 70 min after ingesting the fat (P less than 0.02). The anticholinergic drug, clidinium bromide, inhibits the early increase in spike activity after both meals. However, the anticholinergic has no effect on the delayed peak of activity following the ingestion of fat. This study suggests that (a) the early gastrocolic response to a standard meal and a fat meal is cholinergically mediated and (b) the late increase in rectosigmoidal motility occurs only after fat ingestion and may be controlled by other neural mediators or possibly the gastrointestinal hormones.

Adult↗

Pathophysiology of infection with Ostertagia ostertagi in cattle.

Infection with the abomasal nematode, Ostertagia ostertagi, is an important cause of impaired productivity in young cattle in temperate parts of the world. Such losses have been associated with marked changes in feed intake, gastrointestinal function, protein, energy and mineral metabolism, and in body composition. The reduction in feed intake is an important factor in the pathogenesis of infection and may account for a large part of the difference in weight gain between ad libitum fed control and infected calves. Despite the obvious importance of inappetance, only recently has an association been made between reduced intake, altered gut motility and elevated levels of certain gastrointestinal hormones, such as gastrin. It has been suggested that the elevated gastrin levels accompanying abomasal parasitism may impair reticulo-ruminal motility and slow down abomasal emptying, leading to a stasis of ingesta and a reduction in feed intake. The rise in blood gastrin levels may also be partly responsible for the marked hyperplasia of the fundic mucosa seen in abomasal infections. Pronounced changes in protein metabolism have also been associated with Ostertagia infection. Radioisotopic studies have demonstrated increased losses of albumin into the gastrointestinal tract which are accompanied by an increase in the rate of synthesis in the liver. Dietary protein breakdown in the abomasum is also likely to be impaired, although there is evidence of a compensatory increase in protein digestion in the lower gut of parasitised calves. Increased losses of albumin are not always accompanied by increases in faecal nitrogen, suggesting that albumin is broken down and recycled as ammonia. Radioisotopic studies in animals with intestinal nematode infections have demonstrated a marked reduction in muscle protein synthesis and an increase in protein synthesis in gastrointestinal tissue. Such changes in the balance of protein synthesis are likely to be brought about by alterations in the balance of certain metabolic hormones. Marked changes in energy metabolism also accompany Ostertagia infection. Parasitised calves exhibit a marked increase in non-esterified fatty acid levels, resulting from the mobilisation of adipose tissue, and a reduction in digestive efficiency of energy, probably associated with the increase in cycling of protein through the gastrointestinal tract and the compensatory increases in protein synthesis. Mineral metabolism may also be affected although relatively little work has been conducted in cattle. Changes in body composition reflect a reduction in deposition of muscle protein and fat, and an increase in bone content and water retention.

Animals↗

Hormones and receptors in gastrointestinal malignancies.

Receptors for several polypeptide hormones have been demonstrated in cells of the gastrointestinal tract and pancreas. Some of these polypeptides stimulate or inhibit cell division. Therefore, these receptors have been sought in carcinomas arising from these tissues, and several examples have been reported. In some instances, stimulation of tumor growth by the corresponding ligand has been demonstrated or blocked by a receptor antagonist. In experimental carcinogenesis, the incidence of tumors has been influenced by some of the same hormones. Receptors and binding proteins for steroid hormones also have been reported in carcinomas of the pancreas. Manipulation of sex steroid hormones has yielded both inhibition and enhancement of growth of human and rat pancreatic cancers. These observations imply that trophic or growth inhibiting polypeptide and steroid hormones may serve as promoters or inhibitors of carcinogenesis in gastrointestinal organs and may influence the growth of established carcinomas. Receptor blockers may provide a clinical approach for slowing the growth of some gastrointestinal cancers.

Animals↗

Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects.

CONTEXT: The mechanisms underlying weight loss after Roux-en-Y gastric bypass (RYGBP) are not well understood. OBJECTIVE: The objective of the study was to assess the changes in active glucagon-like peptide 1 (GLP-1) and total peptide YY (PYY) after RYGBP and examine their relationship with changes in hunger and satiety. DESIGN: This was a prospective study on the changes in active GLP-1, PYY, hunger, and satiety in response to a standardized test meal in nine normal-glucose-tolerant obese subjects [body mass index (BMI) 47.4 +/- 6.1 kg/m(2)] before and 6 wk after RYGBP. RESULTS: Before surgery, meal ingestion failed to stimulate GLP-1 and PYY secretion. Six weeks after surgery, despite subjects still being markedly obese (BMI 43.6 +/- 7.8 kg/m(2)), the area under the curve(0-120') of GLP-1 and of PYY in response to the standardized test meal were significantly elevated (P < 0.05 and P < 0.01, respectively). These hormonal responses were significantly larger (P < 0.01) than those observed in a group matched for the BMI attained 6 wk after surgery. The 2.9 +/- 1.2- and 1.6 +/- 1.9-fold increase, respectively, in the area under the curve(0-120') of GLP-1 and PYY were accompanied by a significant decrease in fasting (P < 0.05) and postprandial hunger (P = 0.05) and a significant increase in satiety (P < 0.05) after meal intake. Nevertheless, a significant correlation between changes in the hormonal and eating behavior parameters was not found. CONCLUSION: Our data show that RYGBP is associated with an improvement in the active GLP-1 and total PYY response to a liquid-meal intake. Moreover, we provide circumstantial evidence for a potential role of these gastrointestinal hormones on the decreased appetite after RYGBP.

Adult↗

Cholecystokinin- and gastrin-induced protein and amylase secretion from the parotid gland of the anaesthetized rat.

I.V. infusion of pentagastrin (20 microg/kg/h) or cholecystokinin (CCK)-8 (1 microg/kg/h) for 10 min caused secretion of salivary proteins from the parotid gland in the anaesthetized rat without any accompanying overt fluid secretion. This "occult" response was revealed by a subsequent wash-out injection of methacholine (5 microg/kg, I.V.) 10 min after the end of the infusion period (aiming at avoiding synergistic interactions). While the fluid response to methacholine was unaffected by the preceding infusion of pentagastrin and CCK-8, the output of protein increased by 147% (pentagastrin) and 74% (CCK-8) and that of amylase by 45% (CCK-8) compared to the responses to methacholine upon saline infusion. Those increases were abolished by the CCK-A receptor blocker (lorglumide), but not by the CCK-B receptor blocker (itriglumide). Evisceration, combined sympathetic and parasympathetic denervation of the glands and assay under adrenoceptor blockade excluded contribution from the gastro-intestinal tract, central or ganglionic mechanisms and circulating catecholamines to the increase in protein/amylase. Furthermore, Western blot demonstrated CCK receptors for both A and B subtypes in normal and chronically denervated glands. In the submandibular gland, both pentagastrin and CCK-8 evoked a trace secretion of saliva but, under the present experimental set-up, no statistically significant increase in protein output. Thus, in addition to the autonomic nervous system, gastrointestinal hormones may, in some types of glands, be involved in the secretion of salivary gland proteins.

Amylases↗

Renal function during bovine neurotensin infusion in man.

The peptide hormone neurotensin (NT) is found mainly in gut endocrine cells of the ileum, but has also been identified as a putative neurotransmitter in the central and peripheral nervous systems. It may have a dual role as a circulating gastrointestinal hormone and peripheral neurotransmitter. Its predominant effects are to reduce oesophageal sphincter tone, inhibit gastric secretion and emptying and inhibit intestinal motility, but stimulate intestinal and pancreatic exocrine secretion; NT-like immunoreactivity has been found in kidney and therefore NT may influence renal function. When infused i.v. in rabbits it causes antinatriuresis. We have studied its renal effects in 11 healthy males by i.v. infusion under conditions of altered dietary sodium. Postprandial circulating neurotensin levels were reproduced by infusion. There were no consistent systemic or renal haemodynamic effects. Plasma electrolytes and renin did not change. Only renal chloride excretion changed significantly, falling by ca. 30%, and recovering after infusion. There is no evidence for a specific renal tubular chloride transport mechanism, but coupled cotransport, Na+:K+:2CI-, may be hormonally regulated. NT might stimulate this process and contribute to the renal response to changes in dietary composition, especially sodium intake.

Adult↗

Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones.

Using animal models of acinar and ductal pancreatic cancer, we investigated the effect of analogs of hypothalamic hormones on tumor growth. In Wistar/Lewis rats bearing the acinar pancreatic tumor DNCP-322, chronic administration of [L-5-Br-Trp8]somatostatin-14 significantly decreased tumor weights and volume. Somatostatin-28 and the cyclic hexapeptide analog of somatostatin cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) failed to influence the growth of this tumor. The agonistic analog of luteinizing hormone-releasing hormone [D-Trp6]LH-RH also significantly decreased tumor weight and volume in this model and reduced testosterone levels and the weights of the ventral prostate and tests. In Syrian hamsters bearing ductal type of pancreatic carcinoma, chronic administration of [L-5-Br-Trp8]somatostatin diminished tumor weights and volume. The percentage change in tumor volume was significantly decreased when compared to control animals. In one experiment, cyclic hexapeptide of somatostatin also inhibited growth of this tumor. [D-Trp6]LH-RH, given twice daily or injected in the form of microcapsules for constant controlled release, significantly decreased tumor weight and volume and suppressed serum testosterone levels. Hamsters castrated 4 days after transplantation of the pancreatic tumors showed a significant decrease in weight and volume of these tumors. This suggests that pancreatic cancers may, at least in part, be sex hormone sensitive. [D-Trp6]LH-RH may decrease the growth of pancreatic carcinomas by suppressing androgens. Somatostatin analogs reduce the growth of pancreatic ductal and acinar cancers, probably by inhibiting the release or stimulatory action of gastrointestinal hormones on tumor cells (or both). Inhibition of animal models of pancreatic tumors by chronic administration of somatostatin analogs and [D-Trp6]LH-RH suggests that these compounds should be considered for the development of a new hormonal therapy for cancer of the pancreas.

Animals↗

Incretins and the development of type 2 diabetes.

The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are released in response to nutrient ingestion and potentiate glucose-stimulated insulin secretion from pancreatic beta cells. The augmentation of postprandial insulin secretion by such gastrointestinal hormones is called the incretin effect. The incretin effect is almost completely absent in patients with type 2 diabetes. This is due to 1) an approximate 15% reduction in postprandial GLP-1 secretion and 2) a near total loss of insulinotropic activity of GIP. This review article summarizes clinical studies on abnormalities in the secretion and insulinotropic effects of GIP and GLP-1 in patients with type 2 diabetes as well as in individuals at high risk. A significant proportion of first-degree relatives are characterized by a reduced insulinotropic response to exogenous GIP. Nevertheless, this phenomenon does not predispose to a more rapid deterioration in glucose tolerance or conversion to impaired glucose tolerance or diabetes. Therefore, although there are hints of early abnormalities in incretin secretion and action in prediabetic populations, it has not been proven that such phenomena are central to the pathogenesis of type 2 diabetes.

Animals↗

Octreotide enhances the accelerating effect of erythromycin on gastric emptying in healthy subjects.

BACKGROUND: Erythromycin exhibits gastrokinetic properties through cholinergic pathways. Reports regarding the action of octreotide on gastric emptying are conflicting. AIM: : To assess: (i) the hypothesis that serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying; and (ii) any modification of the gastrokinetic action of erythromycin induced by octreotide. SUBJECTS AND METHODS: Gastric emptying of a standard meal was estimated in 20 healthy subjects by scintigraphy on three different occasions in a double-blind, placebo-controlled manner and in random order: (i) after placebo; (ii) after 200 mg of intravenous erythromycin; and (iii) after 200 mg of intravenous erythromycin following pre-treatment with either 4 mg of intravenous ondansetron (10 subjects) or 50 micro g octreotide. RESULTS: Erythromycin significantly accelerated gastric emptying in all subjects by abolishing the lag phase. Pre-treatment with ondansetron abolished the accelerating effect of erythromycin by restoring the emptying times to placebo levels. Octreotide significantly enhanced the accelerating effect of erythromycin by reducing both the lag and post-lag phases of gastric emptying. CONCLUSIONS: Serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying. This effect seems to be enhanced by pre-treatment with octreotide, possibly as a result of the modification of the gastrointestinal hormonal environment.

Adult↗

Proximal gastric motor and sensory function in slow transit constipation.

BACKGROUND: Slow transit constipation may be part of a more generalized gastrointestinal motility disorder. METHODS: Gastric motor and sensory function were evaluated using a barostat in 17 patients with slow transit constipation and in 16 healthy controls. A step-wise isobaric distension procedure was performed, followed by a barostat procedure including a liquid meal. Symptoms were scored using visual analog scales. Plasma levels of gastrointestinal hormones were determined postprandially. RESULTS: Proximal gastric compliance was significantly reduced in the patients. Basal gastric volume did not differ between patients and controls. Postprandial fundus relaxation was significantly reduced in the patients and correlated significantly with daily upper gastrointestinal symptoms. Postprandial secretion of cholecystokinin and gastrin was reduced in the patients. CONCLUSIONS: In patients with slow transit constipation, proximal gastric compliance is reduced and postprandial fundus relaxation is impaired. These findings support the hypothesis that slow transit constipation may be part of a pan-enteric disorder.

Adult↗

Relationship between diseases of the pancreas and hyperplasia of Brunner's glands.

Examination of 105 duodeno-pancreatectomy specimens showed that 75% of the cases of chronic pancreatitis (n = 74) manifested diffuse hyperplasia of Brunner's glands. In pancreatitis involving part of the pancreas in the presence of ducts of the embryonic type (n = 6), in segmental pancreatitis (n = 16), and in pancreatic cancer (n = 23), no significant difference in the thickness of the layer of Brunner's glands was found as compared with normal specimens. There was no statistically significant correlation between the degree of hyperplasia of Brunner's glands and the degree of scarring of the exocrine pancreatic parenchyma. Nor was there any correlation between existence and extent of scarring of the duodenal wall, inflammatory infiltration of the duodenal mucosa, duration of disease, consumption of alcohol and history of gall stones and ulcers in patients with and without hyperplasia of Brunner's glands. Diffuse hyperplasia of the duodenal glands is probably an adaptive reaction to the exocrine insufficiency of the pancreas or the changes in gastric function (hyperacidity, accelerated emptying of the stomach) caused by chronic pancreatitis. A fact which supports this statement is that the inhibitor hormone urogastrone--an inhibitor of gastric acid secretion--is formed in Brunner's glands. The question is also discussed whether chronic pancreatitis and hyperplasia of Brunner's glands might not also develop simultaneously in the presence of disturbances of the gastrointestinal hormones, themselves either primary or due to alcohol consumption.

Alcoholism↗