Gastric Inhibitory Polypeptide Release Research Articles

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs.

It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models for preterm infants. Pigs were given either total parenteral nutrition (TPN, n = 14) or slowly advancing volumes (16-64 ml·kg(-1)·day(-1)) of preterm infant formula (IF, n = 15) or bovine colostrum (BC, n = 13), both given as adjunct to parenteral nutrition. On day 5, both enteral diets increased intestinal mass (27 ± 1 vs. 22 ± 1 g/kg) and glucagon-like peptide 2 release, relative to TPN (P < 0.05). The incidence of mild NEC lesions was higher in IF than BC and TPN pigs (60 vs. 0 and 15%, respectively, P < 0.05). Only the IF pigs showed reduced gastric emptying and gastric inhibitory polypeptide release, and increased tissue proinflammatory cytokine levels (IL-1β and IL-8, P < 0.05) and expression of immune-related genes (AOAH, LBP, CXCL10, TLR2), relative to TPN. The IF pigs also showed reduced intestinal villus-to-crypt ratio, lactose digestion, and some plasma amino acids (Arg, Cit, Gln, Tyr, Val), and higher intestinal permeability, compared with BC pigs (all P < 0.05). Colonic microbiota analyses showed limited differences among groups. Early feeding with formula induces intestinal dysfunction whereas bovine colostrum supports gut maturation when mother's milk is absent during the first week after preterm birth. A diet-dependent feeding guideline may be required for newborn preterm infants.

Glycemic responses, appetite ratings and gastrointestinal hormone responses of most common breads consumed in Spain. A randomized control trial in healthy humans.

The present study was carried out to determine the glycemic index (GI), glycemic load (GL), insulinemic index (InI), appetite ratings and postprandial plasma concentrations of gastrointestinal hormones related to the control of food intake after the ingestion of the five most common breads consumed in Spain with different compositions and manufacturing processes. Twenty-two healthy adults participated in a randomized crossover study. The breads tested were Ordinary, Precooked-Frozen, Candeal-flour, Alfacar whites and Wholemeal. All breads portions were calculated to supply 50 g of available carbohydrates. In addition, 50 g of glucose was used as a reference. A linear mixed-effects model was used to compare data calculated for all breads with glucose load. The GI value varied from 61 for the Wholemeal, to Alfacar 68, Ordinary 76, and 78 and 86 for the Precooked-Frozen and Candeal-flour breads, respectively. Wholemeal and Alfacar had lower GI than glucose. All tested breads had a lower GL (ranged 9 to 18) compared with glucose. Wholemeal GL was similar to Alfacar, but lower than the other white breads. InI were significantly lower for all breads (ranged 68 to 73) compared with glucose, and similar among them. The intake of the Wholemeal bread led to a higher release of gastric inhibitory polypeptide compared with the Ordinary and Precooked breads and to a higher release of pancreatic polypeptide compared with the Precooked-Frozen bread. All breads affected appetite ratings similarly. In conclusion, based on GL, the Wholemeal bread would be expected to exert a favorable glycemic response.

Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion.

Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K cells in response to nutrient intake, especially fat. GIP is one of the contributing factors inducing fat accumulation that results in obesity. A recent study shows that fatty acid-binding protein 5 (FABP5) is expressed in murine K cells and is involved in fat-induced GIP secretion. We investigated the mechanism of fat-induced GIP secretion and the impact of FABP5-related GIP response on diet-induced obesity (DIO). Single oral administration of glucose and fat resulted in a 40% reduction of GIP response to fat but not to glucose in whole body FABP5-knockout (FABP5(-/-)) mice, with no change in K cell count or GIP content in K cells. In an ex vivo experiment using isolated upper small intestine, oleic acid induced only a slight increase in GIP release, which was markedly enhanced by coadministration of bile and oleic acid together with attenuated GIP response in the FABP5(-/-) sample. FABP5(-/-) mice exhibited a 24% reduction in body weight gain and body fat mass under a high-fat diet compared with wild-type (FABP5(+/+)) mice; the difference was not observed between GIP-GFP homozygous knock-in (GIP(gfp/gfp))-FABP5(+/+) mice and GIP(gfp/gfp)-FABP5(-/-) mice, in which GIP is genetically deleted. These results demonstrate that bile efficiently amplifies fat-induced GIP secretion and that FABP5 contributes to the development of DIO in a GIP-dependent manner.

Adaptation of the Secretion of Gastric Acid and Gastric Inhibitory Peptide in Response to Propylthiouracil

The purpose of this study was designed to investigate the effects of the intravenous (IV) infusion of propylthiouracil (PTU) on basal and pentagastrin-stimulated gastric acid secretion (GAS), as well as plasma concentrations of gastric inhibitory polypeptide (GIP), and calcium (Ca(superscript 2+)). The polyethylene (PE) tubes were inserted into the esophagus, pylorus, right femoral and jugular veins as luminal and vascular exits respectively in adult male rats. Basal GAS was collected for 45 min before IV infusion of alkaline saline (2 ml/h, control group) or PTU (20 mg/ml/ 300 g BW, experimental group) for 45 min. Infusion of pentagastrin (8 μg/ml/300 g BW) was added for 90 min following infusion of alkaline saline or PTU for an additional 45 min. IV infusion of PTU increased the concentrations of plasma thyroid-stimulating hormone (TSH) and GIP but decreased the level of plasma Ca(superscript 2+) in male rats. Neither the basal nor the pentagastrin-evoked levels of gastric acid secretion were altered by the IV infusion of PTU. These results suggested that the unchanged gastric acid secretion in male rats after IV administration of PTU was at least in part due to an adaption of gastric acid secretion to PTU caused by increased release of GIP and decreased level of plasma calcium.

Engineered Enteroendocrine Cells Secrete Insulin in Response to Glucose and Reverse Hyperglycemia in Diabetic Mice

Type 1 diabetes is a metabolic disorder caused by loss of insulin-producing pancreatic beta-cells. Expression of insulin in non-beta-cells to create beta-cell surrogates has been tried to treat type 1 diabetes. Enteroendocrine K cells have characteristics similar to pancreatic beta-cells, such as a glucose-sensing system and insulin-processing proteases. In this study, we genetically engineered an enteroendocrine cell line (STC-1) to express insulin under the control of the glucose-dependent insulinotropic polypeptide promoter. We screened clones and chose one, Gi-INS-7, based on its high production of insulin. Gi-INS-7 cells expressed glucose transporter 2 (GLUT2) and glucokinase (GK) and secreted insulin in response to elevated glucose levels in vitro. To determine whether Gi-INS-7 cells can control blood glucose levels in diabetic mice, we transplanted these cells under the kidney capsule of streptozotocin (STZ)-induced diabetic mice and found that blood glucose levels became normal within 2 weeks of transplantation. In addition, glucose tolerance tests in mice that became normoglycemic after transplantation with Gi-INS-7 cells showed that exogenous glucose was cleared appropriately. These results suggest that engineered K cells may be promising surrogate beta-cells for possible therapeutic use for the treatment of type 1 diabetes.

Biology of Incretins: GLP-1 and GIP

This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The published literature was reviewed, with emphasis on recent advances in our understanding of the biology of GIP and GLP-1. GIP and GLP-1 are both secreted within minutes of nutrient ingestion and facilitate the rapid disposal of ingested nutrients. Both peptides share common actions on islet beta-cells acting through structurally distinct yet related receptors. Incretin-receptor activation leads to glucose-dependent insulin secretion, induction of beta-cell proliferation, and enhanced resistance to apoptosis. GIP also promotes energy storage via direct actions on adipose tissue, and enhances bone formation via stimulation of osteoblast proliferation and inhibition of apoptosis. In contrast, GLP-1 exerts glucoregulatory actions via slowing of gastric emptying and glucose-dependent inhibition of glucagon secretion. GLP-1 also promotes satiety and sustained GLP-1-receptor activation is associated with weight loss in both preclinical and clinical studies. The rapid degradation of both GIP and GLP-1 by the enzyme dipeptidyl peptidase-4 has led to the development of degradation-resistant GLP-1-receptor agonists and dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes. These agents decrease hemoglobin A1c (HbA1c) safely without weight gain in subjects with type 2 diabetes. GLP-1 and GIP integrate nutrient-derived signals to control food intake, energy absorption, and assimilation. Recently approved therapeutic agents based on potentiation of incretin action provide new physiologically based approaches for the treatment of type 2 diabetes.

Effect of GIP, GLP-1, insulin and gastrin on ghrelin release in the isolated rat stomach

Ghrelin release in man depends on the macronutrient composition of the test meal. The mechanisms contributing to the differential regulation are largely unknown. To elucidate their potential role, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), insulin, gastrin and somatostatin were examined on isolated rat stomach ghrelin secretion, which offers the advantage of avoiding systemic interactions. Basal ghrelin secretion was in a range that did not permit to consistently evaluate inhibiting effects. Therefore, the effect of gastrointestinal hormones and insulin was analyzed during vagal prestimulation. GLP-1(7–36)amide 10 −8 and 10 −7 M decreased ghrelin secretion significantly. In contrast, GIP 10 −8 and 10 −7 M augmented not only prestimulated, but also basal ghrelin secretion ( p<0.05). Insulin reduced ghrelin at 10 −10, 10 −8 and 10 −6 M ( p<0.05). Both gastrin 10 −8 M and somatostatin 10 −6 M also significantly inhibited ghrelin secretion. These data demonstrate that GLP-1(7–36)amide, insulin, gastrin and somatostatin are potential candidates to contribute to the postprandially observed inhibition of ghrelin secretion with insulin being the most effective inhibitor in this isolated stomach model. GIP, on the other hand, could attenuate the postprandial decrease. Because protein-rich meals do not effectively stimulate GIP release, other as yet unknown intestinal factors must be responsible for protein-induced stimulation of ghrelin release.

Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy.

Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown. An interesting model for the study of hormonal perturbations accompanying marked insulin resistance without concomitant diabetes is myotonic dystrophy (DM1). The work was carried out in an out-patient setting. An oral glucose tolerance test was performed in 18 males with DM1 and 18 controls to examine the release of incretins and counter-regulatory hormones. Genetic analyses were also performed in patients. We found that the increment in GLP-1 after oral glucose was significantly greater in patients, while there was no significant difference in GIP or glucagon responses between patients and controls, although long CTG repeat expansions were associated with a more pronounced GIP response. Interestingly, the GLP-1 response to oral glucose correlated with the insulin response in patients but not in controls whereas, in controls, the insulin response closely correlated with the GIP response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions. This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1 patients and that CTG triplet repeats are linked to GIP release. These abnormalities may contribute both to the severe insulin resistance and hyperinsulinemia in DM1 and to the preservation of adequate islet function, enabling glucose tolerance to be normal in spite of this marked insulin resistance in DM1.

Misoprostol-Inhibited Rat Gastric Emptying Is Independent of Gastric Inhibitory Polypeptide Release

We studied the effects of orally or intraperitoneally administrated misoprostol on rat gastric emptying and looked what was the role of gastric inhibitory polypeptide (GIP) in this emptying. The rats initially received oral misoprostol at doses of 1, 10, 50, and 100 μg/kg. Another group of rats received misoprostol intraperitonally at doses of 10, 50, 250, and 500 μg/kg. Using an oral radiochromium motility marker, the liquid gastric emptying was measurement 30 min after misoprostol treatment. The plasma GIP levels were measured by a home-made radioimmunoassay kit. Oral treatments at the doses of 1 and 10 μg/kg did not influence emptying, whereas other doses delayed emptying (p < 0.01). Except the 10- μg/kg injection, other doses exhibited a dose-dependent inhibition in emptying (p < 0.01). Neither oral feeding nor intraperitoneal injection changed plasma GIP levels. We conclude that liquid gastric emptying is disturbed after various routes of misoprostol treatment; GIP appears less important in the misoprostol-mediated gastric emptying.

GLP-1 Release in Man after Lower Large Bowel Resection or Intrarectal Glucose Administration

Background: This study addresses the question whether the insulinotropic gut hormone, glucagon-like peptide-1 (GLP-1), is released from the lower large bowel upon oral or rectal glucose uptake. Methods: It was evaluated whether rectum or sigmoid colon resection alters glucose homeostasis or the plasma levels of the insulinotropic gut hormone, gastric inhibitory polypeptide (GIP), or GLP-1. Six men and 3 women (age 63 ± 8 years, BMI 25.4 ± 4.0 kg/m²) with normal preoperative fasting glucose values were treated before and after resection of large bowel segments. Fasting oral glucose tolerance (OGT, 75 g glucose/300 ml) tests were performed both before and 10 days postoperatively. Another approach aimed to clarify whether luminal glucose stimulation in the rectum/sigmoid colon increases GLP-1 plasma levels. Ten healthy volunteers (4 males, 6 females, age 25 ± 2 years, BMI 22.1 ± 2.4 kg/m²) received enemas with both saline and, 7 days later, 1 g/kg body weight glucose (70% glucose solution) intrarectally. Results: Neither rectum nor sigmoid colon resection led to significant changes in the pre- and postoperative glucose responses to OGT testing, or insulin, GIP and GLP-1 release. Intrarectal glucose instillation increased blood glucose by about 10 mg/dl with parallel small elevations in immunoreactive insulin and immunoreactive C peptide. However, plasma GLP-1 levels remained unaltered. Conclusion: Our data make it unlikely that GLP-1 derived from the lower large bowel contributes significantly to maintain normal glucose tolerance.

Inhibitory effects of hyperglycaemia on fed jejunal motility: potential role of hyperinsulinaemia

Acute hyperglycaemia is known to inhibit jejunal interdigestive motility. This study was undertaken to establish the effects of hyperglycaemia on fed jejunal motility and small intestinal transit time, and to establish if the effects of hyperglycaemia are mediated in part by hyperinsulinaemia. Nine healthy male volunteers were studied in random order using three experimental conditions: (a) euglycaemic clamp [glucose 5 mmol L(-1)]; (b) hyperglycaemic clamp [glucose 15 mmol L(-1)]; and (c) euglycaemic hyperinsulinaemic clamp [glucose 5 mmol L(-l)]. Fed jejunal motility was induced by an intrajejunal perfusion of lipid (Lipofundin medium-chained triglyceride 10%) at 1.5 mL min(-1) [1.5 kcal min(-1)] for 180 min through the most proximal port of a manometry catheter (eight ports spaced at 2-cm intervals) located just distal to the ligament of Treitz. One minute after starting the lipid perfusion, 15 g of lactulose dissolved in 20 mL of tap water was infused. Small intestinal transit time was measured by the hydrogen breath test. Acute hyperglycaemia reduced the total number of jejunal contractions and progradely propagated contractions, the motility index (P < 0.05) and the mean amplitude of contractions and delayed intestinal transit time. Hyperinsulinaemia reduced the total number of jejunal contractions, motility index (P < 0.05) and intestinal transit time. Thus, hyperinsulinaemia may contribute to the inhibitory effects of hyperglycaemia on jejunal motility. In addition, this study demonstrated that intrajejunal infusion of lipid stimulates sustained glucagon-like peptide-1 release. In contrast to fat-induced gastric inhibitory polypeptide release, this glucagon-like peptide-1 release is not inhibited by exogenous or endogenous hyperinsulinaemia (P = 0.59).

Chronic bile diversion to the urinary bladder enhances cholecystokinin release and suppresses gastric inhibitory polypeptide release in dogs.

The role of intestinal luminal bile on cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) release was examined in dogs with chronic external bile diversion. In 6 mongrel dogs, cholecysto-jejuno-cystostomy (C-J-C) was performed using a small segment of the middle small intestine interposed between the gallbladder and urinary bladder with section of the common bile duct. Butter dissolved in 30 ml of lukewarm water was orally ingested before surgery, and same amount of butter solution with or without graded volumes of canine bile were orally ingested between four to six weeks after C-J-C surgery. Increases in both plasma triglyceride and GIP levels after butter ingestion were almost completely abolished by C-J-C, but they were restored by oral bile feeding in a volume-dependent manner. Both basal and fat-stimulated CCK release were enhanced significantly by C-J-C, and oral bile feeding inhibited fat-stimulated CCK release by bile in a dose dependent manner. These data suggest that intraluminal bile regulates basal and fat-stimulated CCK release and fat-stimulated GIP release in dogs.

Gastric inhibitory polypeptide release from a tumor-derived cell line.

A cell line derived from intestinal tumors of transgenic mice (STC-1) was subcloned to produce a stable line with approximately 30% immunoreactive gastric inhibitory polypeptide (irGIP)-containing cells (STC 6-14). High-performance liquid chromatography (HPLC) of STC 6-14 extracts indicated that the tumor cell-derived irGIP had the same retention time as synthetic porcine GIP-(1-42) (pGIP). Approximately 30% of the cells also contained immunoreactive somatostatin (irSS), which eluted as a single peak on HPLC, corresponding with SS-(1-14). On average, each well of extracted cells (5.0 x 10(5) cultured 4 days) contained 33.3 +/- 1.4 ng irGIP and 18.4 +/- 1.5 ng irSS. Basal release of irGIP in the presence of 5 mM glucose was 733 +/- 58 pg.ml cells-1.2h-1 (2.20 +/- 0.17% of total cell content; TCC) and doubled at 20 mM glucose (4.20 +/- 0.42% TCC). The response to glucose was augmented by addition of a SS neutralizing antibody (SOMA-10) and suppressed by 10 nM SS. Basal release of irSS in 5 mM glucose was 377 +/- 35 pg.ml cells-1.2h-1 (2.05 +/- 0.19% TCC) and was increased by glucose (> or = 15 mM) and the addition of pGIP (> or = 1 nM). The STC 6-14 cell line represents a model to study the synthesis, storage, and release of GIP and SS in a controlled environment.

Secretion of gastric inhibitory polypeptide in patients with bile duct obstruction.

The direct contribution of bile to gastric inhibitory polypeptide (GIP) release and the role of bile in regulating GIP secretion in response to fat ingestion are still obscure. The present study was aimed to clarify the influence of bile on GIP release. Seven patients with obstruction of the common bile duct and nine volunteers participated in the study. Fifty milliliters of Lipomul was ingested, and GIP was measured serially for 180 min. After intraduodenal instillation of pooled autologous bile for 2 days, the same study was carried out. The fat-stimulated GIP response was significantly lower in the patients than in the controls. The basal GIP level did not change on bile instillation, but the GIP response to fat ingestion was significantly increased on bile instillation compared with that in the absence of bile. Intraluminal bile alone does not stimulate the secretion of GIP, but it promotes GIP secretion in response to fat ingestion.

Release of gastric inhibitory polypeptide from cultured canine endocrine cells.

Canine intestinal duodenal and jejunal epithelial cell preparations enriched for endocrine cells were obtained by sequential collagenase digestion and centrifugal elutriation and maintained in culture for a 40-h period. Adherent cells contained a total cell content (TCC) of 11.5 +/- 2.5 ng (mean +/- SE) immunoreactive gastric inhibitory peptide (IRGIP)/well and 1.4 +/- 0.2 ng immunoreactive somatostatin (IRS)/well. Release experiments were performed by incubation of the cells with various stimuli over a 2-h period. Basal release of IRGIP in 5 mM glucose-5 mM K+ was 2.7 +/- 0.4% TCC. Incubation with concentrations of K+ > 20 mM or glucose > 15 mM significantly increased IRGIP release, as did the addition of a somatostatin immunoneutralizing antibody to the basal media. The addition of the Ca2+ ionophore, A-23187 (10 microM), or the adenylate cyclase activator, forskolin (100 microM), resulted in an IRGIP output greater than four times basal. Porcine gastrin-releasing peptide (GRP), at 1-100 nM, significantly stimulated IRGIP release in a concentration-dependent fashion. IRS release was increased significantly by 55 mM K+, 20 mM glucose, 10 microM A-23187, 100 nM GRP, or 100 microM forskolin.

Gastric Inhibitory Polypeptide and Insulin Responses to Orally Administered Amino Acids in Genetically Obese Hyperglycemic (ob/ob) Mice

The effects of oral administration of eight L-amino acids (alanine, arginine, cysteine, glycine, histidine, hydroxyproline, lysine and threonine) individually or as an amino acid mixture on plasma gastric inhibitory polypeptide (GIP), insulin and glucose concentrations were examined in 18-h fasted obese hyperglycemic (ob/ob) mice. At a dose of 5.4 mmol/kg body weight, arginine, cysteine, histidine and the amino acid mixture were equipotent in terms of increasing plasma GIP and insulin concentrations. Alanine, hydroxyproline and lysine also increased plasma GIP, but insulin concentrations were unchanged. In contrast, threonine failed to affect either GIP or insulin concentrations. There was no correlation between either the incremental or integrated GIP and insulin responses, and none of the amino acids administered affected circulating glucose concentrations. The results indicate that a range of essential and nonessential neutral and basic amino acids stimulate the release of GIP in ob/ob mice. However, GIP made only a modest contribution to the stimulation of insulin secretion following administration of amino acids in the presence of basal glycemia.

Hyperglycaemia but not hyperinsulinaemia prevents the secretion of glucagon-like peptide-1 (7-36 amide) stimulated by fat ingestion

The effect of insulin and glucose on fat-induced gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1 (7-36 amide)) was studied in five healthy subjects during continuous glucose infusion (Protocol 1) and during hyperinsulinaemic euglycaemic blood glucose clamp (Protocol 2). In Protocol 1, 50 g fat was orally ingested and glucose was infused at a rate of 0.7 g/kg/h for 2 h continuously from the time of fat ingestion. Either glucose infusion alone or fat ingestion alone was carried out in the same subjects as the control. The release of GIP and GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state. In protocol 2, 50 g of fat was ingested and insulin was infused at a rate of 0.1 U/kg/h with an artificial pancreas system to obtain the normoglycaemic hyperinsulinaemic state. The release of GIP was significantly suppressed in the normoglycaemic hyperinsulinaemic state as well as in the hyperglycaemic hyperinsulinaemic state. However, the release of GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state but not in the euglycaemic hyperinsulinaemic state. Thus, it is concluded that insulin inhibits fat-induced GIP, but not GLP-1 (7-36 amide), secretion and that glucose is likely to inhibit GLP-1 (7-36 amide) secretion.

Terbutaline, A β2-Adrenoreceptor agonist, inhibits gastric acid secretion and stimulates release of peptide YY and gastric inhibitory polypeptide in dogs

Terbutaline, a beta 2-adrenoreceptor agonist, inhibits pentagastrin-stimulated gastric acid secretion. The purpose of this study was to examine the effect of intravenous administration of terbutaline on plasma levels of peptide YY (PYY) and gastric inhibitory polypeptide (GIP), both of which are known to inhibit gastric acid secretion. Seven dogs with gastric and duodenal fistulas were given pentagastrin (1 microgram/kg/hr) intravenously for 150 min in combination with terbutaline (10 or 20 micrograms/kg/hr) or saline during the 60- to 120-min period of pentagastrin infusion. Pentagastrin-stimulated gastric acid secretion was significantly (P less than 0.05) inhibited by intravenous administration of terbutaline. Terbutaline significantly increased plasma PYY levels, 24% in response to terbutaline at 10 micrograms/kg/hr, and 59% at 20 micrograms/kg/hr. Plasma GIP levels were also increased significantly, 24% with terbutaline at 10 micrograms/kg/hr, and 39% at 20 micrograms/kg/hr. Our data suggest that terbutaline-induced inhibition of pentagastrin-stimulated gastric acid secretion is mediated, at least in part, by the release of PYY and GIP. The adrenergic nervous system may influence gastric acid secretion through the release of PYY and GIP.

GIP and insulin release in relation to gastric emptying of a mixed meal in man

To clarify the role of GIP (gastric inhibitory polypeptide) as an incretin, we related temporally the gastric emptying of fat, protein and glucose to plasma levels of glucose, GIP and insulin in man. Five healthy volunteers with a multiple lumen duodenal tube ingested a mixed meal with phase-specific markers for the the aqueous phase, liquid fat and the solid protein phase. Duodenal passage was determined by intraduodenal infusion of a second set of phase-specific non-absorbable markers. Plasma insulin rose rapidly from a basal value of 59 pM to 300 pM at 60 min, and then declined to reach basal levels after 180 min. By contrast, plasma GIP rose more slowly than insulin, from a basal value of 9.4 pM, and remained elevated, in the range of 14–18 pM, throughout the 240 min observation period. The time course of plasma insulin concentration paralleled gastric emptying of the aqueous phase, containing most of the meal's glucose ( r = 0.952, P < 0.001). The time course of plasma GIP concentrations paralleled the gastric emptying of fat and protein ( r = 0.763−0.834; P < 0.01−0.05). Plasma insulin concentrations showed no correlation to the rate of emptying of fat and protein ( r = 0.142−0.420; n.s.) and to plasma levels of GIP ( r = 0.365; n.s.). The threshold for plasma glucose at which GIP would exert an incretin effect was only reached at one time point, 30 min after ingestion of the meal. Our findings of simultaneously tracked gastric emptying of meal nutrients, hormone release and plasma glucose levels do not support an important physiological role for GIP as an insulinotropic hormone after ingestion of mixed meals in man.

Stimulation of Gastric Inhibitory Polypeptide Release in ob/ob Mice by Oral Administration of Sugars and Their Analogues

The effect of oral administration of sugars and their analogues (glucose, galactose, fructose, mannose, sucrose, N-acetylglucosamine, 2-deoxyglucose, 3-O-methylglucose and alpha-methyl-glucoside) on plasma gastric inhibitory polypeptide (GIP) concentration was examined in 18-h fasted ob/ob mice. Administration of sucrose (5.52 mol/kg body wt), or the monosaccharides (11.04 mol/kg body wt) glucose, galactose or fructose, elicited prompt GIP responses that peaked at 30 min. Similar effects were induced by 3-O-methylglucose or alpha-methyl-glucoside, but the stimulatory action of 2-deoxyglucose was delayed. In contrast to the other sugars, N-acetylglucosamine decreased plasma GIP concentration, while mannose exerted no effect. The results suggest that sugars using the Na+ glucose contransporter at the luminal brush border stimulate GIP release without the necessity of being metabolized or removed from the cell by the glucose transporter at the basolateral membrane. The ability of fructose to stimulate GIP release in ob/ob mice suggests that the Na+-glucose contransporter does not represent an exclusive trigger for sugar-induced GIP secretion.