Gastric Inhibitory Polypeptide, C-Peptide and Insulin: Secretory Responses of Healthy Volunteers to Standard Carbohydrate Loads

1979 ◽  
Vol 56 (3) ◽  
pp. 23P-23P ◽  
Author(s):  
S. Sykes ◽  
L. M. Morgan ◽  
S. M. Hampton ◽  
V. Marks
Keyword(s):  
Healthy Volunteers ◽  
Gastric Inhibitory Polypeptide ◽  
C Peptide

The Entero-Insular Axis in Polycystic Ovarian Syndrome

1996 ◽  
Vol 33 (3) ◽  
pp. 190-195 ◽  
Author(s):  
R Garaa ◽  
F Norris ◽  
J Wright ◽  
L Morgan ◽  
S Hampton ◽  
...  
Keyword(s):  
Polycystic Ovarian Syndrome ◽  
Gastric Inhibitory Polypeptide ◽  
Tolerance Test ◽  
Normal Weight ◽  
Immunoreactive Insulin ◽  
Oral Glucose ◽  
Hepatic Extraction ◽  
C Peptide ◽  
Molar Ratios ◽  
Ovarian Syndrome

We investigated the contributions made by the entero-insular axis, proinsulin and the fractional hepatic extraction of insulin to the hyperinsulinaemia characteristic of polycystic ovarian syndrome (PCOS). We measured plasma glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (7–36 amide) (GLP-17–36 amide), immunoreactive insulin (IRI), intact proinsulin (IPI), and C-peptide concentrations during a 75 g oral glucose tolerance test in seven normal weight women with PCOS and eight healthy women. Women with PCOS had higher fasting ( P = 0·05) and integrated ( P < 0·01) IRI concentrations than controls. Fasting C-peptide levels were similar in both groups but integrated C-peptide ( P < 0·05) concentrations were greater in PCOS subjects than controls. Fasting and integrated concentrations of glucose, GIP and GLP-17–36 amide were similar in subjects with PCOS and controls. Although fasting IPI concentrations were similar in both groups, integrated IPI concentrations were higher ( P = 0·05) in patients with PCOS. Women with PCOS had similar fasting but higher ( P <0·05) integrated IRI: C-peptide molar ratios than controls. Fasting and integrated IPI: IRI molar ratios were similar in both groups. These results confirm that lean women with PCOS have peripheral hyperinsulinaemia. The mild fasting hyperinsulinaemia is due to increased pancreatic secretion, whereas the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and reduced fractional hepatic extraction of insulin. Hyperproinsulinaemia is modest and appropriate in PCOS. GIP and GLP-17–36 amide do not contribute to the stimulated hyperinsulinaemia in PCOS.

scholarly journals Modifications of gastric inhibitory polypeptide (GIP) secretion in man by a high-fat diet

1988 ◽  
Vol 59 (3) ◽  
pp. 373-380 ◽  
Author(s):  
L. M. Morgan ◽  
S. M. Hampton ◽  
J. A. Tredger ◽  
R. Cramb ◽  
V. Marks
Keyword(s):  
Glucose Tolerance ◽  
Energy Intake ◽  
Plasma Glucose ◽  
High Fat Diet ◽  
Gastric Inhibitory Polypeptide ◽  
Oral Glucose ◽  
Fat Intake ◽  
High Fat ◽  
C Peptide ◽  
Glucose Levels

1. Five healthy volunteers (usual fat intake 103) (SE 9) g/d and energy intake 9855 (SE 937) kJ/d were given on two separate occasions (a) 100 g oral glucose and (b) sufficient intravenous (IV) glucose to obtain similar arterialized plasma glucose levels to those after oral glucose.2. Subjects increased their fat intake by 68 (SE 9·6) % for 28 d by supplementing their diet with 146 ml double cream/d (fat intake on high-fat diet (HFD) 170 (SE 8) g/d; energy intake 12347 (SE 770)).3. The 100 g oral glucose load was repeated and IV glucose again given in quantities sufficient to obtain similar arterialized blood glucose levels. Immunoreactive plasma insulin, C-peptide and gastric inhibitory polypeptide (GIP) were measured.4. Plasma GIP levels were higher following oral glucose after the HFD (area under plasma GIP curve 0–180 min 1660 (SE 592) v. 2642 (SE 750) ng/l.h for control and HFD respectively; P < 0·05). Both insulin and C-peptide levels were significantly higher after oral than after IV glucose (P < 0·01) but neither were affected by the HFD. Glucose levels were lower following the HFD after both oral and IV glucose (area under plasma glucose curve 0–180 min, following oral glucose 6·7 (SE 0·3) mmol/l.h for control and 4·2 (SE 0·6) mmol/l.h for HFD; P < 0·01).5. Glucose-stimulated GIP secretion was thus enhanced by the HFD. Insulin secretion in response to oral glucose was unchanged, in spite of an improvement in glucose tolerance.6. The improvement in glucose tolerance post-HFD could possibly be due to a GIP-mediated inhibition of hepatic glycogenolysis, or a decreased rate of glucose uptake from the small intestine.

Gastroenteropancreatic hormonal changes during exercise

1980 ◽  
Vol 239 (3) ◽  
pp. G136-G140 ◽  
Author(s):  
J. Hilsted ◽  
H. Galbo ◽  
B. Sonne ◽  
T. Schwartz ◽  
J. Fahrenkrug ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Physiological Role ◽  
Gastric Inhibitory Polypeptide ◽  
Molar Ratio ◽  
Immunoreactive Insulin ◽  
Hormonal Changes ◽  
C Peptide ◽  
Exercise Induced ◽  
Normal Men ◽  
Induced Changes

Peripheral plasma concentrations of gastroenteropancreatic peptides were measured during a 3-h period of bicycle exercise at 40% of maximal oxygen uptake in six normal men. Marked increases (P < 0.02) were found in vasoactive intestinal polypeptide (VIP) [1.8 +/- 0.7 (rest) vs. 22.3 +/- 5.4 pmol x l-1 (mean +/- SE) (3 h)], secretin (0.5 +/- 0.5 vs. 11.1 +/- 2.7 pmol x l-1), pancreatic polypeptide (PP) (4.0 +/- 1.5 vs. 46.3 +/- 11.5 pmol x l-1), somatostatin (SRIF) (12.8 +/- 1.2 vs. 17.7 +/- 0.6 pmol x l-1), whereas no changes occurred in gastric inhibitory polypeptide (37.3 +/- 5.9 vs. 39.2 +/- 9.8 pmol x l-1). Immunoreactive insulin and C-peptide decreased from 0.08 +/- 0.004 and 0.39 +/- 0.03 pmol x l-1, respectively, to 0.04 +/- 0.003 (P < 0.005) and 0.13 +/- 0.02 (P < 0.001). The significant decrease in C-peptide and in the C-peptide-to-insulin molar ratio indicate decreased insulin secretion and clearance, respectively, during exercise. Plasma glucose decreased [5.0 +/- 0.1 (rest) vs. 4.2 +/- 0.3 mmol.l-1 (3 h)] (P < 0.01). During 3 h of rest, none of the measured parameters had changed. The marked exercise-induced changes in plasma concentrations of PP, secretin, VIP, and SRIF are provocative. We know in detail neither the stimuli for the release of these peptides nor their physiological role during exercise.

Gastro-entero-pancreatic hormones in amniotic fluid from normal and diabetic pregnant women

1986 ◽  
Vol 113 (3_Suppl) ◽  
pp. S37-S43
Author(s):  
F. Fallucca ◽  
P. Gargiulo ◽  
F. Troili ◽  
D. Zicari ◽  
G. Pimpinella ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Pregnant Women ◽  
Cell Function ◽  
Neonatal Morbidity ◽  
Gastric Inhibitory Polypeptide ◽  
Molar Ratio ◽  
Arginine Test ◽  
C Peptide ◽  
Low Concentrations ◽  
The Status

Abstract. Clinical applications of analyses of hormones in amniotic fluid (AF) have recently been increased. In diabetic pregnancy, determinations of insulin and C-peptide in AF have been suggested as good indicators of the status of the foetus. We have investigated the pancreatic alpha and beta cell function by measuring insulin (IRI), C-peptide (CPR), glucagon (IRG), somatostatin (SLI), and gastric inhibitory polypeptide (GIP) in amniotic fluid collected during basal conditions or 2 h after an arginine test in 92 diabetic and 32 nondiabetic pregnant women. During basal conditions, in diabetic pregnant women, IRI, CPR and the insulin: glucagon molar ratio (I/G) were all significantly higher while amniotic fluid-IRG was significantly lower than in the controls. After arginine stimulation, IRI increased in AF of the diabetic pregnant women but not in AF of the controls while no differences were observed in AF-GIP and AF-SLI concentrations. Higher IRI and CPR, as well as lower IRG values were significantly related to poor maternal metabolic control. The occurrence of neonatal morbidity including macrosomia was significantly associated with increased AF, IRI and CPR concentrations after an arginine challenge and these factors were the most sensitive predictors of neonatal morbidity in infants of diabetic mothers. Increased AF glucose concentrations and I/G ratios were related to neonatal hypoglycaemia; jaundice and respiratory distress syndrome were associated to low concentrations of SF-IRG.

Reduction of hepatic insulin clearance after oral glucose ingestion is not mediated by glucagon-like peptide 1 or gastric inhibitory polypeptide in humans

2007 ◽  
Vol 293 (3) ◽  
pp. E849-E856 ◽  
Author(s):  
Juris J. Meier ◽  
Jens J. Holst ◽  
Wolfgang E. Schmidt ◽  
Michael A. Nauck
Keyword(s):  
Gastric Inhibitory Polypeptide ◽  
Insulin Clearance ◽  
Oral Glucose ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Glucose Administration ◽  
Glucose Ingestion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Hepatic Insulin Clearance

Changes in hepatic insulin clearance can occur after oral glucose or meal ingestion. This has been attributed to the secretion and action of gastric inhibitory polypeptide (GIP) and glucagon-like peptide (GLP)−1. Given the recent availability of drugs based on incretin hormones, such clearance effects may be important for the future treatment of type 2 diabetes. Therefore, we determined insulin clearance in response to endogenously secreted and exogenously administered GIP and GLP-1. Insulin clearance was estimated from the molar C-peptide-to-insulin ratio calculated at basal conditions and from the respective areas under the curve after glucose, GIP, or GLP-1 administration. Oral glucose administration led to an ∼60% reduction in the C-peptide-to-insulin ratio ( P < 0.0001), whereas intravenous glucose administration had no effect ( P = 0.09). The endogenous secretion of GIP or GLP-1 was unrelated to the changes in insulin clearance. The C-peptide-to-insulin ratio was unchanged after the intravenous administration of GIP or GLP-1 in the fasting state ( P = 0.27 and P = 0.35, respectively). Likewise, infusing GLP-1 during a meal course did not alter insulin clearance ( P = 0.87). An inverse nonlinear relationship was found between the C-peptide-to-insulin ratio and the integrated insulin levels after oral and during intravenous glucose administration. Insulin clearance is reduced by oral but not by intravenous glucose administration. Neither GIP nor GLP-1 has significant effects on insulin extraction. An inverse relationship between insulin concentrations and insulin clearance suggests that the secretion of insulin itself determines the rate of hepatic insulin clearance.

Role of gastric inhibitory polypeptide in postprandial hyperinsulinemia of obesity

1988 ◽  
Vol 254 (6) ◽  
pp. E767-E774 ◽  
Author(s):  
L. R. Roust ◽  
M. Stesin ◽  
V. L. Go ◽  
P. C. O'Brien ◽  
R. A. Rizza ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Kinetic Model ◽  
Healthy Subjects ◽  
Gastric Inhibitory Polypeptide ◽  
Volume Of Distribution ◽  
Insulin Clearance ◽  
C Peptide ◽  
Obese Subjects ◽  
Secretion Rates

To assess the contribution of gastric inhibitory polypeptide (GIP) to the postprandial hyperinsulinemia of obesity, secretion rates of GIP (generated from kinetic analyses from infusions of porcine GIP) and insulin (from C-peptide applied to a validated kinetic model) to meals of 3 sizes were determined in 10 obese (5 male and 5 female) and 10 lean, sex- and age-matched healthy subjects. Although the postprandial secretion rates of GIP were greater in obese subjects (P = 0.03), postprandial concentrations of GIP were not. The latter may be explained by the greater volume of distribution of GIP in obese subjects (P = 0.036). Secretion rates and volume of distribution of GIP were correlated (r = 0.652, P less than 0.01). Despite excessive integrated postprandial (P = 0.010) insulin concentrations, insulin secretion was not significantly different between obese and lean subjects. We conclude that 1) although postprandial plasma GIP concentrations are normal, GIP secretion is increased in obesity, 2) the postprandial hyperinsulinemia of obesity is not due to excessive insulin secretion but is likely secondary to altered insulin clearance, and 3) GIP cannot account for the hyperinsulinemia of obesity through its insulinotropic action.

Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

2004 ◽  
Vol 286 (4) ◽  
pp. E621-E625 ◽  
Author(s):  
Juris J. Meier ◽  
Oliver Goetze ◽  
Jens Anstipp ◽  
Dirk Hagemann ◽  
Jens J. Holst ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Repeated Measures ◽  
Venous Blood ◽  
Area Under The Curve ◽  
Gastric Inhibitory Polypeptide ◽  
Time Pattern ◽  
C Peptide ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1 ◽  
Meal Ingestion

The insulinotropic gut hormone gastric inhibitory polypeptide (GIP) has been demonstrated to inhibit gastric acid secretion and was proposed to possess “enterogastrone” activity. GIP effects on gastric emptying have not yet been studied. Fifteen healthy male volunteers (23.9 ± 3.3 yr, body mass index 23.7 ± 2.3 kg/m2) were studied with the intravenous infusion of GIP (2 pmol·kg-1·min-1) or placebo, each administered to the volunteers on separate occasions from -30 to 360 min in the fasting state. At 0 min, a solid test meal (250 kcal containing [13C]sodium octanoate) was served. Gastric emptying was calculated from the 13CO2 exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA and one-way ANOVA. During the infusion, GIP rose to steady-state concentrations of 159 ± 15 pmol/l for total and 34 ± 4 pmol/l for intact GIP ( P < 0.0001). Meal ingestion further increased GIP concentrations in both groups, reaching peak levels of 265 ± 20 and 82 ± 9 pmol/l for total and 67 ± 7 and 31 ± 9 pmol/l for intact GIP during the administration of GIP and placebo, respectively ( P < 0.0001). There were no differences in glucose, insulin, and C-peptide between the experiments with the infusion of GIP or placebo. Gastric half-emptying times were 120 ± 9 and 120 ± 18 min ( P = 1.0, with GIP and placebo, respectively). The time pattern of gastric emptying was similar in the two groups ( P = 0.98). Endogenous GIP secretion, as derived from the incremental area under the curve of plasma GIP concentrations in the placebo experiments, did not correlate to gastric half-emptying times ( r2 = 0.15, P = 0.15 for intact GIP; r2 = 0.21, P = 0.086 for total GIP). We conclude that gastric emptying does not appear to be influenced by GIP. The secretion of GIP after meal ingestion is not suppressed by its exogenous administration. The lack of effect of GIP on gastric emptying underlines the differences between GIP and the second incretin glucagon-like peptide 1.

scholarly journals Insulin and glucose metabolism with olanzapine and a combination of olanzapine and samidorphan: exploratory phase 1 results in healthy volunteers

2021 ◽  
Author(s):  
Frederico G. S. Toledo ◽  
William F. Martin ◽  
Linda Morrow ◽  
Carine Beysen ◽  
Daiva Bajorunas ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Healthy Volunteers ◽  
Exploratory Study ◽  
The Body ◽  
Metabolic Effects ◽  
Oral Glucose ◽  
C Peptide ◽  
Bipolar I Disorder ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

AbstractA combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine’s unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder.

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

2017 ◽  
Vol 313 (5) ◽  
pp. E622-E630 ◽  
Author(s):  
Elena Previti ◽  
Serenella Salinari ◽  
Alessandro Bertuzzi ◽  
Esmeralda Capristo ◽  
Stephan Bornstein ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glycemic Control ◽  
Granger Causality ◽  
Metabolic Surgery ◽  
Gastric Inhibitory Polypeptide ◽  
Oral Glucose ◽  
Healthy Controls ◽  
Nonesterified Fatty Acids ◽  
C Peptide ◽  
Glucagon Like Peptide 1

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.

Effects of Acarbose on the relationship between changes in GIP and insulin responses to meals in normal subjects

1986 ◽  
Vol 112 (3) ◽  
pp. 361-366 ◽  
Author(s):  
Per-Henrik Groop ◽  
Leif Groop ◽  
Karl Johan Tötterman ◽  
Frej Fyhrquist
Keyword(s):  
Positive Relationship ◽  
Insulin Response ◽  
Gastric Inhibitory Polypeptide ◽  
Normal Subjects ◽  
Glucose Response ◽  
C Peptide ◽  
Acarbose Treatment ◽  
Concomitant Reduction ◽  
Insulin Responses ◽  
The Relationship

Abstract. The relationship between changes in gastric inhibitory polypeptide (GIP), C-peptide and insulin responses to meals was studied in 8 normal subjects after 2 weeks of Acarbose treatment. Acarbose caused a significant reduction of GIP and insulin responses (P <0.05). The decrease in insulin response could not be explained by changes in the glycaemic stimulus of insulin secretion, as Acarbose did not significantly change the plasma glucose response to meals during the study. The reduced insulin response was seen without a concomitant reduction in the C-peptide response to the meals, thus resulting in a decreased insulin/C-peptide ratio after Acarbose treatment (P < 0.05). The changes in GIP response after Acarbose correlated positively with the change in insulin/C-peptide ratio (r = 0.69; P < 0.05). Our data thus challenge the concept that Acarbose therapy affects the secretion of insulin. The positive relationship between changes in GIP response and changes in the insulin/C-peptide ratio rather suggests that GIP affects the metabolism of insulin or C-peptide.

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