Plasma Gastric Inhibitory Polypeptide Levels Research Articles

Glycemic control after metabolic surgery: a Granger causality and graph analysis.

The purpose of this study was to examine the contribution of nonesterified fatty acids (NEFA) and incretin to insulin resistance and diabetes amelioration after malabsorptive metabolic surgery that induces steatorrhea. In fact, NEFA infusion reduces glucose-stimulated insulin secretion, and high-fat diets predict diabetes development. Six healthy controls, 11 obese subjects, and 10 type 2 diabetic (T2D) subjects were studied before and 1 mo after biliopancreatic diversion (BPD). Twenty-four-hour plasma glucose, NEFA, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) time courses were obtained and analyzed by Granger causality and graph analyses. Insulin sensitivity and secretion were computed by the oral glucose minimal model. Before metabolic surgery, NEFA levels had the strongest influence on the other variables in both obese and T2D subjects. After surgery, GLP-1 and C-peptide levels controlled the system in obese and T2D subjects. Twenty-four-hour GIP levels were markedly reduced after BPD. Finally, not only did GLP-1 levels play a central role, but also insulin and C-peptide levels had a comparable relevance in the network of healthy controls. After BPD, insulin sensitivity was completely normalized in both obese and T2D individuals. Increased 24-h GLP-1 circulating levels positively influenced glucose homeostasis in both obese and T2D subjects who underwent a malabsorptive bariatric operation. In the latter, the reduction of plasma GIP levels also contributed to the improvement of glucose metabolism. It is possible that the combination of a pharmaceutical treatment reducing GIP and increasing GLP-1 plasma levels will contribute to better glycemic control in T2D. The application of Granger causality and graph analyses sheds new light on the pathophysiology of metabolic surgery.

Enteral supplementation with glutamine, fiber, and oligosaccharide modulates incretin and glucagon-like peptide-2 secretion.

Aims/IntroductionA dietary supplementation product enriched with glutamine, dietary fiber and oligosaccharide (GFO) is widely applied for enteral nutrition support in Japan. The aim of the present study was to evaluate the effects of GFO ingestion on secretion of incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2).Materials and MethodsWe carried out a cross-over study involving 20 healthy Japanese volunteers. The participants received GFO or 17 g of glucose, the equivalent carbohydrate in GFO as the control. Plasma glucose, serum insulin, and plasma total GIP, total GLP-1 and total GLP-2 levels during GFO or glucose loading were determined.ResultsGFO loading produced significantly higher plasma GLP-1 levels at 30 min and 60 min, area under the curve-GLP-1 value, and area under the curve-GLP-2 value after administration compared with those by glucose loading. In contrast, plasma GIP levels at both 30 and 60 min, and area under the curve-GIP value after glucose loading were significantly higher than those after GFO loading.ConclusionsThese results show that GFO ingestion stimulates GLP-1 and GLP-2 secretion, and reduces GIP secretion compared with glucose ingestion. Therefore, GFO could have an intestinotrophic effect as well as an ameliorating effect on metabolic disorders through modification of release of gut hormones.

Transcriptional Regulatory Factor X6 (Rfx6) Increases Gastric Inhibitory Polypeptide (GIP) Expression in Enteroendocrine K-cells and Is Involved in GIP Hypersecretion in High Fat Diet-induced Obesity

Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K-cells in response to nutrient ingestion. GIP potentiates glucose-stimulated insulin secretion and induces energy accumulation into adipose tissue, resulting in obesity. Plasma GIP levels are reported to be increased in the obese state. However, the molecular mechanisms of GIP secretion and high fat diet (HFD)-induced GIP hypersecretion remain unclear, primarily due to difficulties in separating K-cells from other intestinal epithelial cells in vivo. In this study, GIP-GFP knock-in mice that enable us to visualize K-cells by enhanced GFP were established. Microarray analysis of isolated K-cells from these mice revealed that transcriptional regulatory factor X6 (Rfx6) is expressed exclusively in K-cells. In vitro experiments using the mouse intestinal cell line STC-1 showed that knockdown of Rfx6 decreased mRNA expression, cellular content, and secretion of GIP. Rfx6 bound to the region in the gip promoter that regulates gip promoter activity, and overexpression of Rfx6 increased GIP mRNA expression. HFD induced obesity and GIP hypersecretion in GIP-GFP heterozygous mice in vivo. Immunohistochemical and flow cytometry analysis showed no significant difference in K-cell number between control fat diet-fed (CFD) and HFD-fed mice. However, GIP content in the upper small intestine and GIP mRNA expression in K-cells were significantly increased in HFD-fed mice compared with those in CFD-fed mice. Furthermore, expression levels of Rfx6 mRNA were increased in K-cells of HFD-fed mice. These results suggest that Rfx6 increases GIP expression and content in K-cells and is involved in GIP hypersecretion in HFD-induced obesity.

Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects

Low birth weight (LBW) is associated with an increased risk of insulin resistance and downregulation of oxidative phosphorylation (OXPHOS) genes when exposed to a metabolic challenge of high-fat overfeeding (HFO). To elaborate further on the differential effects of HFO in LBW subjects, we measured in vivo mitochondrial function, insulin secretion, hepatic glucose production, and plasma levels of key regulatory hormones before and after 5 days of HFO in 20 young LBW and 26 normal-birth-weight (NBW) men. The LBW subjects developed peripheral insulin resistance after HFO due to impaired endogenous glucose storage (9.42 ± 4.19 vs. 5.91 ± 4.42 mg·kg FFM(-1)·min(-1), P = 0.01). Resting muscle phosphorcreatine and total ATP in muscle increased significantly after HFO in LBW subjects only, whereas additional measurements of mitochondrial function remained unaffected. Despite similar plasma FFA levels, LBW subjects displayed increased fat oxidation during insulin infusion compared with normal-birth-weight (NBW) subjects after HFO (0.37 ± 0.35 vs. 0.17 ± 0.33 mg·kg FFM(-1)·min(-1), P = 0.02). In contrast to NBW subjects, the plasma leptin levels of LBW subjects did not increase, and the plasma gastric inhibitory polypeptide (GIP) as well as pancreatic polypeptide (PP) levels increased less in LBW compared with NBW subjects during HFO. In conclusion, HFO unmasks dissociation between insulin resistance and mitochondrial dysfunction in LBW subjects, suggesting that insulin resistance may be a cause, rather than an effect, of impaired muscle OXPHOS gene expression and mitochondrial dysfunction. Reduced increments in response to HFO of fasting plasma leptin, PP, and GIP levels may contribute to insulin resistance, lower satiety, and impaired insulin secretion in LBW subjects.

Plasma gastric inhibitory polypeptide and glucagon-like peptide-1 levels after glucose loading are associated with different factors in Japanese subjects.

Aims/Introduction: Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins that potentiate insulin secretion from pancreatic β-cells. The factors responsible for incretin secretion have been reported in Caucasian subjects, but have not been thoroughly evaluated in Japanese subjects. We evaluated the factors associated with incretin secretion during oral glucose tolerance test (OGTT) in Japanese subjects with normal glucose tolerance (NGT). We measured plasma GIP and GLP-1 levels during OGTT in 17 Japanese NGT subjects and evaluated the factors associated with GIP and GLP-1 secretion using simple and multiple regression analyses. GIP secretion (AUC-GIP) was positively associated with body mass index (P < 0.05), and area under the curve (AUC) of C-peptide (P < 0.05) and glucagon (P < 0.01), whereas GLP-1 secretion (AUC-GLP-1) was negatively associated with AUC of plasma glucose (P < 0.05). The insulinogenic index was most strongly associated with GIP secretion (P < 0.05); homeostasis model assessment β-cell was the most the strongly associated factor in GLP-1 secretion (P < 0.05) among the four indices of insulin secretion and insulin sensitivity. Several distinct factors might be associated with GIP and GLP-1 secretion during OGTT in Japanese subjects. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00078.x, 2011).

Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects.

Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important factors in the pathogenesis of type 2 diabetes and have a promising therapeutic potential. Alterations of their secretion, in vivo degradation, and elimination in patients with chronic renal insufficiency (CRI) have not yet been characterized. Ten patients with CRI (aged 47 +/- 15 years, BMI 24.5 +/- 2.2 kg/m(2), and serum creatinine 2.18 +/- 0.86 mg/dl) and 10 matched healthy control subjects (aged 44 +/- 12 years, BMI 24.9 +/- 3.4 kg/m(2), and serum creatinine 0.89 +/- 0.10 mg/dl) were included. On separate occasions, an oral glucose tolerance test (75 g), an intravenous infusion of GLP-1 (0.5 pmol. kg(-1). min(-1) over 30 min), and an intravenous infusion of GIP (1.0 pmol. kg(-1). min(-1) over 30 min) were performed. Venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1 (total and intact), and GIP (total and intact; specific immunoassays). Plasma levels of GIP (3-42) and GLP-1 (9-36 amide) were calculated. Statistics were performed using repeated-measures and one-way ANOVA. After the oral glucose load, plasma concentrations of intact GLP-1 and intact GIP reached similar levels in both groups (P = 0.31 and P = 0.87, respectively). The concentrations of GIP (3-42) and GLP-1 (9-36 amide) were significantly higher in the patients than in the control subjects (P = 0.0021 and P = 0.027, respectively). During and after the exogenous infusion, GLP-1 (9-36 amide) and GIP (3-42) reached higher plasma concentrations in the CRI patients than in the control subjects (P < 0.001 and P = 0.0033, respectively), whereas the plasma levels of intact GLP-1 and GIP were not different between the groups (P = 0.29 and P = 0.27, respectively). Plasma half-lives were 3.4 +/- 0.6 and 2.3 +/- 0.4 min for intact GLP-1 (P = 0.13) and 5.3 +/- 0.8 and 3.3 +/- 0.4 min for the GLP-1 metabolite (P = 0.029) for CRI patients vs. healthy control subjects, respectively. Plasma half-lives of intact GIP were 6.9 +/- 1.4 and 5.0 +/- 1.2 min (P = 0.31) and 38.1 +/- 6.0 and 22.4 +/- 3.0 min for the GIP metabolite (P = 0.032) for CRI patients vs. healthy control subjects, respectively. Insulin concentrations tended to be lower in the patients during all experiments, whereas C-peptide levels tended to be elevated. These data underline the importance of the kidneys for the final elimination of GIP and GLP-1. The initial dipeptidyl peptidase IV-mediated degradation of both hormones is almost unaffected by impairments in renal function. Delayed elimination of GLP-1 and GIP in renal insufficiency may influence the pharmacokinetics and pharmacodynamics of dipeptidyl peptidase IV-resistant incretin derivatives to be used for the treatment of patients with type 2 diabetes.

The entero-insular axis in type 2 diabetes--incretins as therapeutic agents.

The search for intestinal factors regulating the endocrine secretion of the pancreas started soon after the discovery of secretin, i.e. nearly 100 years ago. Insulinotropic factors of the gut released by nutrients and stimulating insulin secretion in physiological concentrations in the presence of elevated blood glucose levels have been named incretins. Of the known gut hormones only gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1 [7-36] amide) fulfill this definition.--The incretin effect (i.e. the ratio between the integrated insulin response to an oral glucose load and an isoglycaemic intravenous glucose infusion) is markedly diminished in patients with type 2 diabetes mellitus, while the plasma levels of GIP and GLP-1 and their responses to nutrients are in the normal range. Therefore, a reduced responsiveness of the islet B-cells to incretins has been postulated. This insensitivity of the diabetic B-cells towards incretins can be overcome by supraphysiological (pharmacological) concentrations of GLP-1 [7-36], however not of GIP. Accordingly, fasting and postprandial glucose levels can be normalized in patients with type 2 diabetes by infusions of GLP-1 [7-36]. Further studies revealed that this is partially due to the fact that GLP-1 [7-36]--in addition to its insulinotropic effect--also inhibits glucagon secretion and delays gastric emptying. These three antidiabetic effects qualify GLP-1 [7-36] as an interesting therapeutic tool, mainly for type 2 diabetes. However, because of its short plasma half life time natural GLP-1 [7-36] is not suitable for subcutaneous application. At present methods are being developed to improve the pharmacokinetics of GLP-1 by inhibition of the cleaving enzyme dipeptidyl peptidase IV (DPP-IV) or by synthesis of DPP-IV resistant GLP-1 analogues. Also naturally occurring GLP-1 analogues (for instance exendin-4) with a much longer half life time than GLP-1 [7-36] are being tested.--Thus, after 100 years of speculations and experimentations, incretins and their analogues are emerging as new antidiabetic drugs.

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.

Reduced gastric inhibitory polypeptide but normal glucagon-like peptide 1 response to oral glucose in postmenopausal women with impaired glucose tolerance.

The gastrointestinal hormones, gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are both released from the gut after oral glucose ingestion and stimulate insulin secretion. This study examined the release of these hormones in subjects with impaired glucose tolerance (IGT), which precedes the development of non-insulin-dependent diabetes. Six postmenopausal women with IGT, aged 59 years, underwent a 75 g oral glucose tolerance test and plasma levels of GIP and GLP-1 were determined regularly during the following 2 h. The results were compared with those in seven age- and weight-matched women with normal glucose tolerance (NGT). Basal plasma levels of GIP and GLP-1 were not different between the groups. In response to the oral glucose ingestion, plasma levels of both GIP and GLP-1 increased in both groups. The plasma GIP increase after glucose ingestion was, however, reduced in women with IGT. Thus, the GIP response as determined as the area under the curve for the 60 min after oral glucose was 34.8 +/- 3.2 pmol/l per min in women with IGT versus 56.4 +/- 7.8 pmol/l per min in those with NGT (P = 0.021). In contrast, the GLP-1 response to oral glucose was not different between the groups. By definition, the glucose response to oral glucose was markedly increased in women with IGT, and the insulin response during the second hour after glucose ingestion was exaggerated. The GIP response to oral glucose is impaired in postmenopausal women with IGT, whereas the plasma GLP-1 response is not affected.

Regulation of thyroid hormones in the secretion of insulin and gastric inhibitory polypeptide in male rats

The effect of thyroid hormones on glucose-induced secretion of gastric inhibitory polypeptide (GIP) and insulin was studied. Male rats were thyroidectomized (Tx) or sham Tx. Sham Tx rats were injected with either propylthiouracil ([PTU] 20 mg/kg intraperitoneally) or saline for 2 weeks. In addition, thyroid-intact rats were injected intravenously with triiodothyronine ([T 3] 5 μg/kg) or saline 10 minutes before an oral glucose load (3.2 g/kg). Blood samples were collected from each animal via a jugular catheter at 0, 10, 20, 30, 45, 60, and 90 minutes following glucose ingestion. Plasma levels of GIP and insulin were measured by specific radioimmunoassays (RIAs). Thyroidectomy-induced hypothyroidism increased the basal level of plasma GIP, but decreased that of insulin. Insulin levels at 10, 20, and 30 minutes following oral glucose were lower in hypothyroid rats than in euthyroid rats. Conversely, GIP levels at 60 and 90 minutes following glucose ingestion in PTU-induced hypothyroid rats were higher than those in euthyroid rats. Furthermore, glucose-stimulated insulin secretion was unaltered by pretreatment with T 3, whereas the glucose-induced increase in plasma GIP was completely abolished by preinjection of T 3 in thyroid-intact rats. These results suggest that thyroid functions are involved in the regulation of insulin and GIP secretion in rats.

The effect of GIP and glucagon-like peptides on intestinal basolateral membrane hexose transport.

The effect of gastric inhibitory polypeptide (GIP) and the related glucagon-like peptides-1 and -2 (GLP-1 and GLP-2) on jejunal basolateral membrane glucose transport was investigated to determine if the upregulation produced by luminal hexoses could be explained by the release of one or more of these peptides. Luminal perfusion of the rat jejunum for 4 h, under pentobarbital sodium anesthesia, with 100 mM D-glucose produced a significant increase in plasma GIP levels. Vascular infusion of saline containing 100-800 pM GIP also increased the maximal transport rate for carrier-mediated glucose uptake in jejunal basolateral membrane vesicles. The effect of vascular 400 pM GIP was maximal after 1 h and maintained out to 4 h. The effect of luminal glucose could be blocked by preinjection with anti-GIP antibodies, whereas an antineurotensin antibody had no effect. Vascular infusion with 800 pM GLP-1-(7-36) amide had no effect, but GLP-2 (400 and 800 pM) increased the D-glucose maximal transport rate. An anti-GLP antibody was able to block the response to luminal glucose.

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.

Treatment With an Oral Proteinase Inhibitor Slows Gastric Emptying and Acutely Reduces Glucose and Insulin Levels After a Liquid Meal in Type II Diabetic Patients

To determine whether an oral trypsin/chymotrypsin inhibitor, POT II, will delay the rate of gastric emptying in recently diagnosed type II diabetic patients and improve their postprandial metabolic parameters. Two gastric emptying studies were performed on each of six type II diabetic patients. During one study, the patient ingested a glucose/protein solution, and during the other study, the patient ingested the same glucose/protein solution with the addition of 1.5 g of POT II, a putative stimulant of cholecystokinin (CCK) release. Each patient served as their own control subject. Each of the two oral solutions were administered to the patients in a counter-balanced order separated by at least 1 week. Serum insulin, plasma glucose, plasma gastric inhibitory polypeptide (GIP) values, and the rate of gastric emptying were all significantly (P < 0.05) decreased over the 2-h testing period when POT II was added to the oral glucose/protein meal. The area under the curve above baseline for glucose with POT II was 75% of the glucose value without POT II. The area under the curve above baseline for insulin with POT II was 68% of the value without POT II. Plasma CCK was significantly increased by POT II 15 min postprandially. A trypsin/chymotrypsin inhibitor, POT II, can delay the rate of gastric emptying, and decrease postprandial plasma glucose levels, GIP levels, and serum insulin levels in type II diabetic patients diagnosed recently. Delay of gastric emptying in diabetic patients may provide a unique or adjunctive approach to the treatment of type II diabetes.

&lt;b&gt;THE RESPONSE OF GASTRIC INHIBITORY POLYPEPTIDE (GIP) TO ORAL GLUCOSE IN CHRONIC PANCREATITIS: A STUDY BY RADIOIMMUNOASSAY FOR HUMAN &lt;/b&gt;&lt;b&gt;GIP &lt;/b&gt;

To investigate the insulinotropic effect of gastric inhibitory polypeptide (GIP) in chronic pancreatitis (CP), we examined the GIP response to 75 g oral glucose in 18 CP patients and 7 normal subjects (controls) by a radioimmunoassay for human GIP. The GIP response of CP patients was correlated with the pancreatic exocrine function which was evaluated by the caerulein-secretin test (CS test). Plasma GIP concentrations following the oral administration of glucose were higher in CP patients than in controls, but the difference was not significant. When CP patients were divided into 3 groups according to their exocrine dysfunction (mild, moderate and severe), plasma GIP levels of CP patients with severe exocrine dysfunction were significantly higher than those of controls

Hypersecretion of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide in obese patients.

Postprandial insulin secretion is modulated by both neural and humoral gastrointestinal insulinotropic factors in addition to the absorbed nutrient. To investigate the involvement of the potent insulinotropic hormones gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1) in the postprandial hyperinsulinaemia of obesity, we examined the changes in plasma levels of GIP and tGLP-1 by an oral glucose tolerance test (OGTT) in nine normal subjects (controls), nine obese subjects without glucose intolerance (Group A), and six obese mild diabetic patients (Group B). Following the OGTT, plasma GIP levels in Group B were increased more markedly than those in the other two groups. Plasma levels of tGLP-1 were estimated by the difference between the values measured with the N-terminal directed antiserum (GLP-1NT) and those with the C-terminal directed antiserum (GLP-1 CT). Plasma levels of GLP-1 NT were increased in Group B, but decreased in the other two groups. Plasma GLP-1 CT levels were increased in all groups with the highest response in Group B. These results suggest that the combined augmentation of plasma GIP and tGLP-1 responses were involved in the delayed and considerable increases in plasma insulin after glucose ingestion in obese diabetic patients. Since tGLP-1 is suppressed in the hyperglycaemic hyperinsulinaemic state in normal subjects, the augmented tGLP-1 response appears to be characteristic of obese Type 2 diabetes.

Differences in glucagon-like peptide-1 and GIP responses following sucrose ingestion

To investigate the mechanism of oral carbohydrate-stimulated secretion of the two most potent incretin candidates, gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1), we studied the changes in the plasma levels of these peptides in five healthy men after sucrose ingestion with or without pretreatment with an α- d-glucosidase inhibitor (AO-128). After sucrose ingestion, plasma levels of GIP peaked at 15 min and remained high up to 120 min. Plasma levels of GLP-1 NT measured with antiserum R1043 (N-terminal specific) tended to decrease gradually and those of GLP-1 CT measured with antiserum R2337 (C-terminal specific) increased. Therefore, estimated plasma levels of tGLP-1 increased markedly within 30 min, then declined slightly over the next 60 min. After treatment with AO-128 (0.6 mg/day) for 1 week, increases in plasma glucose and insulin levels were attenuated and the increase in plasma GIP levels was diminished, while the increase in tGLP-1 levels was sustained much longer. It is concluded that GIP secretion is stimulated by glucose absorption and tGLP-1 secretion by the presence of sucrose in the gut.

The Effect of Duodenojejunal Alimentation on Gastric pH and Hormones in Intensive Care Unit Patients

We evaluated effects of duodenojejunal (DJ) feeding on gastric pH and selected gastrointestinal hormones in 13 randomly selected patients in an intensive care unit (ICU). To obtain baseline values for gastric pH, a nasogastric (NG) tube was placed in each patient and gastric pH was measured every 30 minutes for 2 hours. To obtain control values, a Dobbhoff tube was placed fluoroscopically and 0.45 percent saline solution (NaCl), 75 ml, was infused for 1 hour and gastric pH was measured again; the previously placed NG tube was left in position. Then, by randomization, either 0.45 percent NaCl (pH = 5) was continued (n = 6) or a high-nitrogen, isotonic, enteral feeding solution (Osmolite HN, pH = 6.4) (n = 7) was infused, both at 75 ml/h. Gastric pH was noted hourly for 96 hours; antacid (Maalox TC, 15-ml aliquots) was given by NG tube when the pH was 4 or less. After 96 hours, the infusion was stopped and gastric pH was noted for 4 additional hours. Before and during initial saline solution infusion; after 24, 48, 72, and 96 hours of continuous infusion; and 4 hours after stopping the infusion, peripheral venous blood was obtained for measurement of plasma gastric inhibitory polypeptide (GIP) and serum gastrin. Data were analyzed by ANOVA (RMD), Fishers' exact test, and the unpaired t-test. Groups did not differ demographically. Throughout the infusion, gastric pH tended to be higher with the enteral feeding solution than with saline solution, but this was significant only at 24 hours. Less antacid was required with the enteral feeding solution at 24 and 48 hours than with saline solution. Plasma GIP levels were significantly higher with the enteral feeding solution than with saline solution during most of the infusion. Serum gastrin levels did not differ between the groups. In this cohort, infusion of the enteral feeding solution tended to maintain a gastric pH of more than 4 and was associated with increased plasma GIP levels, which may inhibit gastric acid secretion. Early enteral feeding may benefit certain ICU patients.

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.

Peptide YY inhibits the insulinotropic action of gastric inhibitory polypeptide

Peptide YY (PYY) is released from the gut after ingestion of fat or after a meal. The purpose of this investigation was to examine the effect of PYY on gastric inhibitory polypeptide (GIP)-stimulated insulin release in conscious dogs with gastric and duodenal fistulas. In control experiments, 6 dogs received GIP (400 pmol/kg, i.v., for 1 h) and glucose (0.6 g/kg, i.v., for 1 h); the integrated insulin response over a 1-h period was 142 ± 32.7 ng-60 min/ml. The plasma GIP levels achieved by this procedure were similar to those observed by intraduodenal infusion of Lipomul (2 ml/min), suggesting that the dose of GIP used was within the physiologic range. Intravenous infusion of three different doses of PYY (100, 200, or 400 pmol/kg · h) caused a significant inhibition of insulin release stimulated by GIP + glucose; the integrated insulin response was reduced to 105, 88, and 79 ng-60 min/ml, respectively. On the other hand, PYY (400 pmol/ kg · h) had no effect on insulin secretion induced by intravenous glucose (0.6 g/kg · h) alone. These results indicate that PYY specifically inhibits the insulinotropic action of GIP and that PYY may play a negative-feedback regulatory role in the enteroinsular axis.