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

1997 ◽  
pp. 127-131 ◽  
Author(s):  
B Ahren ◽  
H Larsson ◽  
JJ Holst
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Postmenopausal Women ◽  
Plasma Levels ◽  
Insulin Response ◽  
Gastric Inhibitory Polypeptide ◽  
Oral Glucose ◽  
Glucose Ingestion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

OBJECTIVE: 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. DESIGN AND METHODS: 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). RESULTS: 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. CONCLUSIONS: The GIP response to oral glucose is impaired in postmenopausal women with IGT, whereas the plasma GLP-1 response is not affected.

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 Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1–Mediated Mechanism

2019 ◽  
Vol 104 (8) ◽  
pp. 3481-3490 ◽  
Author(s):  
Alfonso Galderisi ◽  
Cosimo Giannini ◽  
Michelle Van Name ◽  
Sonia Caprio
Keyword(s):  
Glucose Tolerance ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Cell Function ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Double Blind ◽  
Obesity And Diabetes ◽  
Glucose Ingestion

Abstract Context The consumption of high-fructose beverages is associated with a higher risk for obesity and diabetes. Fructose can stimulate glucagon-like peptide 1 (GLP-1) secretion in lean adults, in the absence of any anorexic effect. Objective We hypothesized that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity. Design We studied 14 lean adolescents [four females; 15.9 ± 1.6 years of age; body mass index (BMI), 21.8 ± 2.2 kg/m2] and 23 adolescents with obesity (five females; 15.1 ± 1.6 years of age; BMI, 34.5 ± 4.6 kg/m2). Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and β-cell function [oral disposition index (oDIcpep)]. Eligible subjects received, in a double-blind, crossover design, 75 g of glucose or fructose. Plasma was obtained every 10 minutes for 60 minutes for the measures of glucose, insulin, and GLP-1 (radioimmunoassay) and glucose-dependent insulinotropic polypeptide (GIP; ELISA). Incremental glucose and hormone levels were compared between lean individuals and those with obesity by a linear mixed model. The relationship between GLP-1 increment and oDIcpep was evaluated by regression analysis. Results Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents with obesity exhibited a greater insulin (P &lt; 0.001) and GLP-1 (P &lt; 0.001) increase than did their lean peers. Changes in GIP were similar in both groups. After glucose ingestion, the GLP-1 response (P &lt; 0.001) was higher in the lean group. The GLP-1 increment during 60 minutes from fructose drink was correlated with a lower oDIcpep (r2 = 0.22, P = 0.009). Conclusion Fructose, but not glucose, ingestion elicits a higher GLP-1 and insulin response in adolescents with obesity than in lean adolescents. Fructose consumption may contribute to the hyperinsulinemic phenotype of adolescent obesity through a GLP-1–mediated mechanism.

scholarly journals Glucagon-like peptide 1 and Glucagon-like peptide 2 in relation to osteoporosis in non-diabetic postmenopausal women

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
María Cristina Montes Castillo ◽  
María José Martínez Ramírez ◽  
Rubén Soriano Arroyo ◽  
Isabel Prieto Gomez ◽  
Ana Belén Segarra Robles ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Bone Remodeling ◽  
Plasma Levels ◽  
Dipeptidyl Peptidase ◽  
Mineral Density ◽  
Dipeptidyl Peptidase 4 ◽  
Bone Remodeling Markers ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Osteoporosis Risk

Abstract Osteoporosis results from an imbalance in bone remodeling, which is known to follow a circadian rhythm determined by a functional relationship between intestine and bone tissue. Specific intestinal peptides have been identified as mediators. Glucagon-like peptide 1 and glucagon-like peptide 2, have been associated with bone health. Our main objective was to determine whether postprandial plasma levels of glucagon-like peptide 1, glucagon-like peptide 2 and dipeptidyl-peptidase 4 activity, are associated with osteoporosis in non-diabetic postmenopausal women. We studied non-diabetic postmenopausal women with osteoporosis diagnosed by dual-energy X-ray absorptiometry (cases, n = 43) and age-matched (±1 yr) controls without osteoporosis or a history of osteoporotic fracture (n = 43). We measured postprandial plasma levels of glucagon-like peptide 1, glucagon-like peptide 2, and dipeptidyl-peptidase 4 activity, bone mineral density, and baseline levels of bone remodeling markers and analyzed the food intake using a food-frequency questionnaire. Postprandial glucagon-like peptide 1 values were lower (p < 0.001) in cases, μ (SEM) = 116.25 (2.68), than in controls, μ (SEM) = 126.79 (2.68). Glucagon-like peptide 1 was associated with reduced osteoporosis risk in the crude logistic regression analysis [OR (95% CI) = 0.724 (0.53–0.97), p = 0.031] and adjusted analysis [OR = 0.603 (0.38–0.94), p = 0.027]. We found no association of glucagon-like peptide 2, or dipeptidyl-peptidase 4 activity with osteoporosis. Postprandial glucagon-like peptide 1 levels are related to osteoporosis and osteoporosis risk in non-diabetic postmenopausal women. Further studies are required to verify these findings.

scholarly journals Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2136-2144 ◽  
Author(s):  
Jun Ding ◽  
Yan Gao ◽  
Jing Zhao ◽  
Hong Yan ◽  
Shi-ying Guo ◽  
...  
Keyword(s):  
Food Intake ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Mutant Mouse ◽  
Metabolic Abnormalities ◽  
Metabolic Homeostasis ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
In Vitro Transfection

Heterozygosity for the Pax6 allele is associated with impaired glucose tolerance in humans. With a Pax6 mutant mouse model, we found many of the metabolic abnormalities were consistent with the effects of down-regulating the expression of glucagon-like peptide 1 (GLP-1). In addition to impaired glucose tolerance, adult heterozygous mutant mice (Pax6m/+) secreted less insulin responding to glucose and arginine administration compared with control mice. Moreover, Pax6m/+ mice showed increased food intake compared with control mice, although they were resistant to diet-induced fat accumulation. Indeed, levels of circulating GLP-1 and intestinal transcription of Gcg/Proglucagon were dramatically reduced in Pax6m/+ mice. Mutated Pax6 also failed to activate the Gcg/Proglucagon promoter by in vitro transfection assay. Finally, administering the GLP-1 receptor agonist exendin-4 to Pax6m/+ mice largely reversed their abnormal food intake, glycemic excursion, and insulin secretion. Our studies suggested that disruption of metabolic homeostasis mainly caused by Pax6 haploinsufficiency was mainly mediated by down-regulation of GLP-1. Administration of exendin-4 may be a useful therapy in humans with a similar mutation.

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