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Gastric inhibitory polypeptide: a gut hormone with anabolic functions.

The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), has been isolated and characterized because of its enterogastrone-type effects. It is also named glucose-dependent insulinotropic polypeptide and is actually considered to be the main incretin factor of the entero-insular axis. Besides these well-described effects on gastric secretion and pancreatic beta cells, it also has direct metabolic effects on other tissues and organs, such as adipose tissue, liver, muscle, gastrointestinal tract and brain. In adipose tissue it is involved in the activation and regulation of lipoprotein lipase (LPL); it also inhibits glucagon-induced lipolysis and potentiates the effect of insulin on incorporation of fatty acids into triglycerides. It may play a role in the development of obesity because of the hypersensitivity of adipose tissue of obese animals to some of these actions. In the liver it does not modify insulin extraction, and its incretin effects are due only to the stimulation of insulin secretion and synthesis. It reduces hepatic glucose output and inhibits glucagon-stimulated glycogenolysis. It might increase glucose utilization in peripheral tissues such as muscle. GIP also has an effect on the volume and/or electrolyte composition of intestinal secretion and saliva. The functional importance of its effect on the hormones of the anterior pituitary lobe remains to be established, as it has never been detected in the brain. Its links with insulin are very close and the presence of insulin is sometimes necessary for the greater efficiency of both hormones. GIP can be considered as a true metabolic hormone, with most of its functions tending to increase anabolism.

Adipose Tissue↗

Neurohormonal control of intestinal transit.

This review shows that numerous neuropeptides and hormones are involved in the regulation of intestinal transit. Many gastrointestinal hormones known to act on smooth muscle to influence muscle contractility also play a role in the genesis of abrupt changes associated with alimentary behaviour. In many monogastrics and ruminants, the cyclic occurrence of the migrating motor complex (MMC) is linked to peripheral hormonal factors only slightly influenced by the nature of food. Motilin is the major hormone involved in triggering the gastric migrating motor complex while somatostatine and enkephalins are implicated in the propagation along the small intestine. Other hormones, like CCK8, insulin, gastrin, and neurotensin, trigger the development of an intestinal feed pattern but CCK released at the central nervous system ventromedial hypothalamus is involved in maintaining the postprandial type of activity. Gastrointestinal transit may be altered in physiopathological situations in which CRF, TRH and some cytokines (IL1 beta, TNF alpha) play an important role.

Animals↗

[Hormone producing gastrointestinal neoplasms].

1. Due to their common origin from the neural crest the hormonogenic cells of the intestinal tract show similar cyto-chemical and ultra-structural characteristics. 2. Hyperplasiae and tumors of these cells lead to excessive hormone production with its consequences on the reacting organs. 3. Hormone producing tumors can be confined to one organ only, but as multiple endocrine adenomatosis they can afflict several organs. 4. Diagnosis of most hormone producing tumors is possible with the adequate radio-immunologic tests. Radiologic and endoscopic examinations can contribute to the localization of the tumor. 5. Surgical resection of the tumor or of the reacting organs impaired by the overproduction of hormones from the tumor is the indicated therapy. Medicamentous therapy is rarely successful. 6. The growth of most hormonogenic tumors is relatively slow. Rates of survival of up to 30 years have been known, even after formation of metastases of the tumor. Effects of hormone overproduction on other organs can reduce the prognosis.

Adenoma↗

Gut hormones ghrelin, PYY, and GLP-1 in the regulation of energy balance [corrected] and metabolism.

The first hormone discovered in the gastrointestinal tract was secretin, isolated from duodenal mucosa. Some years later, two additional gastrointestinal hormones, gastrin and cholecystokinin (CCK), were discovered, but it was not until the 1970s that gastrointestinal endocrinology studies became more prevalent, resulting in the discovery of many more hormones. Here, we examine the role of gut hormones in energy balance regulation and their possible use as pharmaceutical targets for obesity.

Animals↗

The effect of oral alcohol on gastroenteropancreatic hormones in volunteers.

This study has examined changes in gastrointestinal hormones induced by alcohol. Ten normal volunteers consumed an orange and carbohydrate-containing drink on two separate occasions, with and without 50g alcohol. There was a significant hyperglycaemia associated with alcohol ingestion but no difference was noted in insulin or gastric inhibitory polypeptide in the two groups. Gastrin release was stimulated by alcohol but pancreatic polypeptide release and N-terminal glucagon release were both suppressed by alcohol. There was no difference in release of secretin or C-terminal glucagon in either group.

Administration, Oral↗

[Multiple analysis on the gastric impetus associated factors in patients with liver cirrhosis].

OBJECTIVE: To investigate mechanism and relation of some disorder motive forces of digest system in patients with liver cirrhosis. METHODS: Plasma vasoactive intestinal peptide (VIP), gastrin and motilin (MTL), electrogastrogram (EGG) and pH value of gastric juice in 24 hours; gastric elimination time by isotope. All above factors have been determined in patients with liver cirrhosis and analyzed with multiple linear regressions. While a group of normal cases has been observed as control. RESULTS: Compared to the control group, higher level of VIP and Gastrin and lower MTL down were observed in liver cirrhosis group (Plasma VIP, Gastrin and MTL are 14.8+/-4.8, 58.6+/-29.8 and 360+/-54.2 separately, t=5.181, 0.05, t=3.871, 0.01 and t=5.529, 0.05 separately). The EGG dominant frequency (DF) and dominant power (DP) decreased around diet; normal slow wave number (N%) decreased and gastric excretion time prolonged, lower bradygastrias (B%) and pH value of 24 hours gastric juice denoted the incline of return movement, there are remarked different with 0.05 or 0.01 separately. Throughout analyzing these factors with multiple linear regressions, there are remarkable relationship between liver cirrhosis and pH value of gastric juice; gastrointestinal hormone and EGG with 0.05 or 0.01. CONCLUSION: (1) There are remarkable gastro esophageal function abnormal which has been conveyed by disorder gastric electric physiology and gastric elimination time in patients with liver cirrhosis. It is suggested that unusual gastrointestinal hormone played an important role during these abnormal process. (2) There is remarkable changing of pH value of 24 hours gastric juice denoted the opposite movement of gastroduodenal juice in patients with liver cirrhosis.

Female↗

Accelerated gastric emptying during hypoglycaemia is not associated with changes in plasma motilin levels.

This study examined whether or not changes in plasma concentrations of motilin and other gastrointestinal hormones known to affect gastric motility are associated with the accelerated gastric emptying seen during hypoglycaemia. While studying gastric emptying by scintigraphy in eight healthy subjects, the plasma concentrations of glucagon, adrenaline, motilin, gastrin, neuropeptide Y and somatostatin were measured during normoglycaemia and hypoglycaemia with simultaneous infusion of either atropine or saline. Blood glucose concentrations were checked by an insulin-glucose clamp. The plasma levels of glucagon and adrenaline increased markedly during both hypoglycaemic examinations compared with normoglycaemia. Neither motilin nor any of the other hormones displayed considerable changes during hypoglycaemia with and without atropine compared with normoglycaemia. No further information about the mechanisms behind the accelerated gastric emptying rate during hypoglycaemia was obtained by analysing motilin and the other gastrointestinal hormones.

Adult↗

[Amino acids as a modulator of hormone secretion].

Amino acids stimulate or inhibit the releases of some pituitary, pancreatic and gastrointestinal hormones by oral or intravenous administration. These effects are clinically used as amino acid loading tests to examine the reserve of hormones, including growth hormone, insulin, glucagon, somatostatin, etc., and of use for the diagnosis of endocrine and gastrointestinal diseases. The mechanism of pituitary hormone release, induced by amino acids, has been explained by their actions on peptidergic and monoaminergic systems in the brain but it is still not known as for pancreatic and gastrointestinal hormones.

Amino Acids↗

Reduced serum cholecystokinin and increase in body fat during oral contraception.

This investigation was undertaken to explore a possible role of the "satiety peptide" cholecystokinin and some other gastrointestinal hormones for changes in appetite and weight during oral contraception. Ten young healthy women attending a youth health care center for contraceptive counseling volunteered for the study. A standardized meal test was used for recordings of appetite and gastrointestinal hormone response before and after 5 months of treatment with a monophasic combined oral contraceptive. Body fat was calculated from measurements of skin-fold thickness. Oral contraceptives caused a suppression of basal levels of serum cholecystokinin, which was correlated to an increase in body fat. Meal-related response of cholecystokinin and appetite were not affected. Serum levels of gastrin and insulin were also unchanged, whereas triglycerides and postprandial glucose levels were elevated. The results suggest a role of cholecystokinin in regulation of body composition. Cholecystokinin stimulates the release of insulin and stimulates lipolysis in adipose tissue. Reduced cholecystokinin levels may, therefore, be related to mild impairment of glucose tolerance and promote body fat storage during oral contraception.

Adipose Tissue↗

Pancreatic reg gene expression is inhibited during cellular differentiation.

BACKGROUND AND OBJECTIVE: Factors that control pancreatic regenerating (reg I) gene expression are unknown, but it is believed that its expression may correspond with cellular differentiation. The authors recently demonstrated that reg I is expressed in AR42J, a rat acinar cell line whose state of differentiation can be modulated by dexamethasone. They used this line to study reg I expression during cellular proliferation and differentiation. METHODS: After treatment of cells with 10 nmol/L dexamethasone, proliferation was assayed by thymidine incorporation; differentiation by expression of elastase I mRNA. Reg I mRNA levels were measured using a rat reg I cDNA probe, and reg I protein levels assayed by enzyme-linked immunosorbent assay of cellular lysates with a polyclonal antibody. The effect of gastrin, cholecystokinin and glucagon on reg I expression was also studied. RESULTS: When compared with controls, treatment with dexamethasone caused thymidine incorporation to decrease and elastase mRNA levels to increase. Reg I mRNA decreased from controls of 100 +/- 16% to 40 +/- 18% (p < 0.05), and reg I protein levels decreased as well. Gastrointestinal hormones had no significant effect on either elastase or reg I gene expression. CONCLUSIONS: Expression of reg I inversely correlates with the level of cellular differentiation, can be modulated via the glucocorticoid receptor, and is a potential marker of gastrointestinal epithelial differentiation. Despite its presence within a pancreatic acinar cell line, reg I gene expression is not modulated by gastrointestinal hormones.

Animals↗

Antroduodenal motility and small bowel transit during continuous intraduodenal or intragastric administration of enteral nutrition.

BACKGROUND: Gastrointestinal intolerance is observed more frequently during intraduodenal (ID) tube feeding than during intragastric (IG) feeding, possibly because it evokes a stronger gastrointestinal response and accelerates small bowel transit. We have investigated whether the accelerated small bowel transit during ID feeding results from alterations in antroduodenal motility pattern. DESIGN: The effect of IG and ID infusion of a polymeric diet (Nutrison, 125 kcal h-1) on antroduodenal motility, small bowel transit time (SBTT) and gastrointestinal hormone release was studied in nine healthy subjects. These subjects were studied on three occasions for 6 h during fasting, continuous IG or ID feeding. RESULTS: Phase III recurrence time was significantly prolonged during IG feeding compared with fasting (240 +/- 51 vs. 136 +/- 24 min; P < 0.05). None of the subjects had recurrence of phase III during ID feeding; the fed motor pattern remained present. Parameters of fed motility (mean amplitude and motility index) were not significantly different between IG and ID feeding, although the frequency of antral and duodenal contractions was lower during ID than during IG feeding. SBTT was significantly accelerated during ID compared with IG feeding and with fasting (58 +/- 8 vs. 73 +/- 9 and 83 +/- 10 min respectively; P < 0.05). Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were significantly higher during ID than during IG feeding. Peptide YY (PYY) levels were significantly higher during ID than during fasting, but not during IG feeding CONCLUSIONS: During intraduodenal feeding, a fed motility pattern is preserved, whereas during intragastric feeding transition from a fed to a fasting motor pattern is observed in over 50% of the subjects. These differences may be related to augmented hormone release during intraduodenal feeding.

Adult↗

GIP increases insulin receptor affinity and cellular sensitivity in adipocytes.

Glucose ingestion has been previously shown to rapidly increase both the affinity of the insulin receptor and the cellular sensitivity of target tissues for insulin. We now demonstrate that gastric inhibitory polypeptide (GIP), a gastrointestinal hormone released by glucose ingestion, can mimic these effects in vitro. Incubation of rat adipocytes with GIP (10-100 ng/ml) resulted in both a displacement to the left of the insulin binding isotherm (i.e., increased receptor affinity) and potentiated insulin-mediated glucose uptake at insulin concentrations less than 1 ng/ml (i.e., increased cellular insulin sensitivity). Cholecystokinin, another gastrointestinal hormone, did not alter the insulin receptor binding characteristics or glucose uptake of the adipocytes in vitro. We suggest that GIP, a known potentiator of glucose-stimulated insulin secretion, may also modulate the effects of insulin by directly altering target tissue sensitivity to insulin.

Adipose Tissue↗

Catabolic effects of gastric bypass in a diet-induced obese rat model.

PURPOSE OF REVIEW: In the USA, 8-10 million people are morbidly obese, which is associated with a high frequency of comorbidities. The most effective treatment is surgery. Of around 180,000 bariatric operations performed in 2005, 80% were Roux-en-Y gastric bypass, consisting of a small gastric pouch to minimize food intake and a Roux-en-Y of distal small bowel bypassing the upper gastrointestinal tract. The precise mechanisms whereby Roux-en-Y gastric bypass achieves sustained weight loss remain unknown. To gain insight into the catabolic events of sustained weight loss we developed a diet-induced obese Roux-en-Y gastric bypass rat model. We review our rat model data from the novel viewpoint of the catabolic state, comparing it with the limited human data available and the catabolic events occurring in cancer anorexia/cachexia syndrome. RECENT FINDINGS: Current data suggest the involvement of mechanisms other than restrictive and malabsorptive factors of the Roux-en-Y gastric bypass, classically thought of as the mechanisms responsible for weight loss. Based on available data, gastrointestinal hormones and cytokines play a key role in reducing food intake and regulating energy homeostasis. Because of the cross talk between peripheral modulators and the hypothalamus, a critical role for their interaction in the outcome of Roux-en-Y gastric bypass is emerging. SUMMARY: In our Roux-en-Y gastric bypass rat model many of the changes in gastrointestinal hormones, adipokines and cytokines as well as in hypothalamic neuropeptides and neurotransmitters resemble the changes observed in the anorexia/cachexia rat model, suggesting that Roux-en-Y gastric bypass triggers a catabolic state responsible for loss of appetite and prolonged body weight reduction.

Animals↗

New directions in the irritable bowel syndrome.

The irritable bowel syndrome (IBS) is an umbrella for the diagnosis of heterogeneous conditions that are awaiting better identification of specific manometric causes. This article focuses on the concept that future therapy for IBS will rely on identification of subgroups and in turn tailor the specific therapeutic approaches to an appreciation of the pathophysiology and symptom predominance of these subgroups. Future therapies will rely on the following principles: (1) prokinetic agents to coordinate upper gastrointestinal and colonic motility as well as improve the propulsive nature of colonic contractions; (2) gastrointestinal hormone agonists such as erythromycin and antagonists such as sandostatin and cholecystokinin antagonists; (3) spasmolytic therapy incorporating calcium channel blocking and anticholinergic agents; (4) inhibition of ovulatory cycle changes in circulating concentrations of gonadal hormones in women, who tend to dominate the IBS population; (5) incorporation of concepts relating to the role of subtypes of 5-hydroxytryptamine receptors in control of neural and myogenic function; (6) reassessment of food intolerance and sensitivity; and (7) incorporation of concepts relating to psychologic profiles and psychologic treatment approaches. IBS is a rich and fertile area for application of the exciting new pharmacologic advances relating to gastrointestinal smooth-muscle and neural innervation of the gut. Improvement in the understanding and treatment of IBS will be one of the major accomplishments of this decade.

Colonic Diseases, Functional↗

Immunocytochemical localization of serotonin in embryos, larvae and adults of the lancelet, Branchiostoma floridae.

Serotonin (5-hydroxytryptamine) is a biogenic amine distributed throughout the metazoans and has an old evolutionary history. It is involved as a developmental signal in the early morphogenesis of both invertebrates and vertebrates, whereas in adults it acts mainly as a neurotransmitter and gastrointestinal hormone. In vertebrates, serotonin regulates the morphogenesis of the central nervous system and the specification of serotonergic as well as dopaminergic neurons. The present study uses, as an experimental model, an invertebrate chordate, the lancelet Branchiostomafloridae, characterized by its remarkable homologies with vertebrates that allows the 'bauplan' of the probable ancestor of vertebrates to be outlined. In particular, the involvement of serotonin as a developmental signal in embryos and larvae, as well as a neurotransmitter and gastrointestinal hormone in adult specimens of Branchiostoma floridae, gives further support to a common origin of cephalocordates and vertebrates.

Animals↗

Effects of gastrointestinal and related hormones on glycogenolysis and gluconeogenesis in cultured liver cells.

When isolated rat liver cells were incubated for 15 min in the presence of vasoactive intestinal peptide, secretin, gastrin, caerulein or glucagon at concentrations ranging from 0.2 microgram to 2 microgram per ml, glycogenolysis was stimulated. Among the gastrointestinal hormones or peptides tested, vasoactive intestinal peptide had the highest stimulatory activity. However, somatostatin was inhibitory for liver glycogenolysis. Combination experiments showed that somatostatin also inhibited the stimulatory effects of vasoactive intestinal peptide and secretin, but not that of glucagon, while glucagon and vasoactive intestinal peptide, or glucagon and secretin showed additive effects on glycogenolysis, but secretin and vasoactive intestinal peptide did not. The results suffest that the receptor site of glucagon is different from those of secretin and vasoactive intestinal peptide. Slight but significant stimulation of gluconeogenesis was also observed by vasoactive intestinal peptide and secretin. The evidence presented in this paper indicates that the so-called enterohepatic axis, in which a part of serum glucose levels is regulated directly by gastrointestinal hormones, exists and that the axis is inhibited by somatostatin.

Animals↗