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.

scholarly journals Glucose-Induced Insulin Hypersecretion in Lipid-Infused Healthy Subjects Is Associated with a Decrease in Plasma Norepinephrine Concentration and Urinary Excretion

2001 ◽  
Vol 86 (10) ◽  
pp. 4901-4907 ◽  
Author(s):  
Christophe Magnan ◽  
Céline Cruciani ◽  
Laurence Clément ◽  
Pierre Adnot ◽  
Mylène Vincent ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Urinary Excretion ◽  
Healthy Subjects ◽  
Plasma Concentrations ◽  
Sympathetic Tone ◽  
Plasma Norepinephrine ◽  
C Peptide ◽  
Lipid Infusion ◽  
Hyperglycemic Clamp ◽  
Glucose Injection

We investigated the effect of a 48 h triglyceride infusion on the subsequent insulin secretion in response to glucose in healthy men. We measured the variations in plasma concentration and urinary excretion of catecholamines as an indirect estimation of sympathetic tone. For 48 h, 20 volunteers received a triglyceride/heparin or a saline solution, separated by a 1-month interval. At time 48 h, insulin secretion in response to glucose was investigated by a single iv glucose injection (0.5 g/kg−1) followed by an hyperglycemic clamp (10 mg·kg−1·min−1, during 50 min). The triglyceride infusion resulted in a 3-fold elevation in plasma free fatty acids and an increase in insulin and C-peptide plasma concentrations (1.5- and 2.5-fold, respectively, P < 0.05), compared with saline. At time 48 h of lipid infusion, plasma norepinephrine (NE) concentration and urinary excretion levels were lowered compared with saline (plasma NE: 0.65 ± 0.08 vs. 0.42 ± 0.06 ng/ml, P < 0.05; urinary excretion: 800 ± 70 vs. 620 ± 25 nmol/24 h, P < 0.05). In response to glucose loading, insulin and C-peptide plasma concentrations were higher in lipid compared with saline infusion (plasma insulin: 600 ± 98 vs. 310 ± 45 pm, P < 0.05; plasma C-peptide 3.5 ± 0.2 vs. 1.7 ± 0.2 nm, P < 0.05). In conclusion, in healthy subjects, a 48-h lipid infusion induces basal hyperinsulinemia and exaggerated insulin secretion in response to glucose which may be partly related to a decrease in sympathetic tone.

Abstract 1924: Carriers of Loss-of-Function Mutations in ABCA1 Display Pancreatic Beta Cell Dysfunction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Menno Vergeer ◽  
Liam R Brunham ◽  
Joris Koetsveld ◽  
Janine K Kruit ◽  
C B Verchere ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Sensitivity Index ◽  
Loss Of Function ◽  
Β Cell ◽  
C Peptide ◽  
Cell Dysfunction ◽  
Time Interaction

Background The ATP Binding Cassette transporter A1 (ABCA1) transports free cholesterol to nascent high-density lipoproteins (HDL) and maintains plasma HDL levels. In mice, ABCA1 is essential in regulating intracellular cholesterol homeostasis and insulin secretion in the β cell. The role of ABCA1 in human glucose metabolism is unclear. Objective and methods To assess the effects of ABCA1 dysfunction on glucose homeostasis in humans , we matched heterozygous carriers of disruptive mutations in ABCA1 and non-carriers for age, gender and BMI and performed oral glucose tolerance tests (OGTT; 9 vs. 8 respectively) and hyperglycemic clamping experiments (6 vs. 6). Results Carriers had lower HDL-C levels than non-carriers (0.58 ± 0.3 vs. 1.46 ± 0.4 mmol/L, p=0.001) but LDL-C did not differ (3.4 ± 1.0 vs. 2.8 ± 0.8 mmol/L, p=0.21). Fasting plasma glucose was not different (5.2 ± 1.5 vs. 5.0 ± 0.4 mmol/L). Glucose curves after OGTT were significantly higher in carriers than in non-carriers (genotype * time interaction, p=0.005; plasma glucose at t=60 min 9.0 ± 3.0 mmol/L vs. 6.0 ± 1.4 mmol/L respectively, p=0.02). During hyperglycemic clamps, carriers showed a lower first phase insulin and C-peptide response than non-carriers (genotype * time interaction, p<0.05 and p<0.01 respectively; insulin at t=5 min 164±118 vs. 352 ±141 pmol/L, p<0.05; C-peptide at t=5 min 1033 ± 628 vs. 1942 ± 723 pmol/L, p<0.05) but no difference in insulin sensitivity index (0.0216 ± 0.012 mg kg −1 . min −1 . pM −1 for carriers and 0.0197 ± 0.005 mg kg −1 . min −1 . pM −1 for non-carriers; p=0.73). Disposition index - a measure of β cell function, adjusted for insulin sensitivity - was lower in carriers than in non-carriers (1037 ± 610 vs. 2718 ± 1524; p<0.05). Non-carriers responded to an arginine stimulus with an increase in C-peptide levels (from 3558 ± 1240 pM to 6817 ± 1665 pM; p<0.005), whereas in carriers this increase did not reach statistical significance (from 3727 ± 1843 pM to 5480 ± 1757 pM; p=0.12). Conclusion Carriers of loss-of-function mutations in ABCA1 show impaired insulin secretion without insulin resistance, resulting in glucose intolerance. Our data confirm previous studies in mice and provide evidence for a role of ABCA1 in β cell dysfunction and the pathophysiology of diabetes mellitus in man.

Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis

1992 ◽  
Vol 83 (5) ◽  
pp. 597-605 ◽  
Author(s):  
Yolanta T. Kruszynska ◽  
Janet Munro ◽  
Philip D. Home ◽  
Neil McIntyre
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Serum Insulin ◽  
Insulin Clearance ◽  
Metabolic Clearance ◽  
Intermediary Metabolites ◽  
C Peptide ◽  
Control Subjects ◽  
Glucose Profiles ◽  
Cirrhotic Patients

1. To examine the contributions of hypersecretion and decreased insulin clearance to the hyperinsulinaemia of cirrhosis, insulin secretion was calculated over the day from serum C-peptide concentrations and C-peptide metabolic clearance rate. The latter was measured during infusions of recombinant human C-peptide. In cirrhotic patients (n = 9) insulin secretion rate was twice that of normal control subjects (n = 10), both in the basal state [02.00–07.00 hours, 15.7 ± 2.1 (mean ± sem) nmol/h (2.6 ± 0.4 units/h) versus 7.0 ± 0.9 nmol/h (1.2 ± 0.2 units/h), P<0.002] and over 24 h [787 ± 93 nmol (132 ± 16 units) versus 346 ± 34 nmol (58 ± 6 units), P<0.001]. However, the area under the serum insulin concentration curve was approximately six times greater in the cirrhotic patients (24 h basal, 6.3 ± 1.0 versus 1.1 ± 0.31 nmol l−1 h, P<0.001; 24 h total, 21.7 ± 3.2 versus 3.7 ± 0.7 nmol l−1 h, P<0.001). Thus, despite impairment of insulin clearance there is continuing hyper-section of insulin in cirrhosis. 2. The relationship of carbohydrate and lipid metabolism with insulin secretion was assessed. In cirrhotic patients, 24 h blood glucose profiles showed a worsening of glucose tolerance over breakfast, despite greater insulin secretion compared with other meals, suggesting that the insulin insensitivity of cirrhosis is worse at this time. 3. Cirrhotic patients showed impaired suppression of blood glycerol levels after meals but normal suppression of serum non-esterified fatty acid concentrations. The greatest differences in the profiles of serum lipids and lipid-related metabolites in cirrhotic patients and control subjects occurred at night. Whereas in control subjects, serum non-esterified fatty acid, blood glycerol and blood 3-hydroxybutyrate concentrations peaked between 01.00 and 03.00 hours, falling gradually thereafter until 08.00 hours, in cirrhotic patients serum non-esterified fatty acid and blood glycerol levels showed a gradual increase during the night to reach maximal levels at 08.00 hours when they were twice those of control subjects (P<0.001). 4. The blood 3-hydroxybutyrate and serum triacyl-glycerol profiles suggested that in cirrhotic patients there was preferential utilization of non-esterified fatty acids for ketogenesis and reduced re-esterification to triacylglycerol.

scholarly journals Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients.

1986 ◽  
Vol 77 (1) ◽  
pp. 98-105 ◽  
Author(s):  
K S Polonsky ◽  
J Licinio-Paixao ◽  
B D Given ◽  
W Pugh ◽  
P Rue ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Diabetic Patients ◽  
Type I ◽  
C Peptide ◽  
Normal Volunteers ◽  
Secretion Rates

scholarly journals Increased insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors

2018 ◽  
Vol 314 (5) ◽  
pp. R639-R646 ◽  
Author(s):  
Andrea Tura ◽  
Roberto Bizzotto ◽  
Yuchiro Yamada ◽  
Yutaka Seino ◽  
Giovanni Pacini ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Clearance ◽  
Second Phase ◽  
Incretin Hormones ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Double Deletion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
First Phase Insulin Secretion

To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO ( n = 31) and wild-type (WT) C57BL6J mice ( n = 45) were intravenously injected with d-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10−3 1/min. After intravenous glucose administration, insulin clearance during first phase insulin secretion was markedly higher in DIRKO than in WT mice (0.68 ± 0.06 10−3 l/min in DIRKO mice vs. 0.54 ± 0.03 10−3 1/min in WT mice, P = 0.02). In contrast, there was no difference between the two groups in insulin clearance during second phase insulin secretion ( P = 0.18). In conclusion, this study evaluated C-peptide kinetics in the mouse and exploited a mathematical model to estimate insulin clearance. Results showed that DIRKO mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.

Determination of Leptin Adiponectin, LDL/HDL ratio with substantial role of Adiponectin and its Receptor

2021 ◽  
Vol 15 (10) ◽  
pp. 2550-2553
Author(s):  
Muhammad Ali Talat ◽  
Muhammad Shoaib ◽  
Sana Sabir ◽  
Uzair Mumtaz ◽  
Ambreen Tauseef ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Elisa Method ◽  
Metabolic Disturbances ◽  
Cross Sectional ◽  
Lipid Status ◽  
History Of ◽  
Obese Subjects ◽  
Suitable Marker

Aim: To determine Leptin/Adiponectin ratio, LDL/HDL ratio and AdipoR1 in obese and healthy subjects along with their respective lipid status. Methods: This cross-sectional comparative study was conducted in Sialkot city. One hundred and thirty-two participants took part in this research. Participants were equally divided into two groups containing non-obese and obese subjects. Mean age was 39.6±0.97 years. Mean BMI for obese subjects was 31.55±0.6 while non-obese group BMI was 20.5±0.2. Individuals with conditions and history of drugs were excluded. Informed and written consent was obtained prior to fasting blood sampling. Serum extraction and proper storage for later testing was carried out. ELISA method used for Adiponectin, AdiopR1 and leptin estimations while lipid profile was determined by Randox Diagnostics kits, using micro lab. SPSS v. 26. was used for comparison between by Mann-Whitney U tes. Results: Higher levels of Leptin/Adiponectin ratio(0.85±0.1) and LDL/HDL ratio (3.39 ± 0.1), serum Adiponectin (545± 73.3 ug/L), leptin (320.7±50.3 pg/mL) and AdipoR1 (28.9± 2.8 ng/mL) in obese when compared with healthy individuals, Leptin/Adiponectin ratio (0.44 ± 0.07 ) and LDL/HDL ratio (2.56 ± 0.08) Adiponectin (834± 70.6 ug/L), AdiopoR1 (17.8± 1.97 ng/mL), leptin (224.4±168.7 pg/mL). Correlation of adiponectin found positive for AdipoR1(r=0.336,p<0.05) and Leptin(r=0263,p<0.05) in obese subjects. L/A ratio correlated positive with leptin (r=0.644,p<0.05) in obese while in healthy subjects (leptin r=0.409,p<0.05,adiponectin r=-0.408,p<0.05 and HDL r=0.266,p<0.05).. Conclusion: The Leptin/Adiponectin ratio was found higher in obese subjects 0.85 as compared to healthy ones 0.44. Also the LDL/HDL ratio was found higher (3.39) when compared to non-obese (2.56), suggesting these ratios as a suitable marker to estimate metabolic disturbances and underlying dyslipidemia in the obese subjects. Key Words: Adiponectin, LDL/HDL ratio, Leptin, Leptin/Adiponectin ratio, Obesity

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.

scholarly journals Dissecting the relationship between obesity and hyperinsulinemia: Role of insulin secretion and insulin clearance

Obesity ◽  
2016 ◽  
Vol 25 (2) ◽  
pp. 378-383 ◽  
Author(s):  
Mee Kyoung Kim ◽  
Gerald M. Reaven ◽  
Sun H. Kim
Keyword(s):  
Insulin Secretion ◽  
Insulin Clearance ◽  
The Relationship

scholarly journals Role Of C- Peptide As A Biomarker For Diabetes – A Mini Review

2019 ◽  
Vol 6 (2) ◽  
pp. 72-75
Author(s):  
Subburaj Bhuvaneshwari ◽  
Ramasamy Amsaveni
Keyword(s):  
Insulin Secretion ◽  
Glucose Level ◽  
Diabetes Type ◽  
The Body ◽  
Insulin Production ◽  
Glucose Content ◽  
C Peptide ◽  
Insulin Synthesis

Diabetes is accumulation of higher glucose content in the blood. When the glucose level is increased it indicates the low insulin secretion or no response to the insulin production in the body. C-peptide is cleaved from the proinsulin chains A and B during insulin synthesis. C- peptide produced in the same amount toinsulin because; C-peptide is removed when insulin is formed. As per the amount is same for both the Cpeptide and insulin, the C-peptide works as a biomarker for finding the insulin secretion and to finding of diabetes type accurately. In this review it has been focused on C-peptide and its role as a biomarker in diabetes and predictor of complications and other risks caused by the diabetes.

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