Context: The "incretin" hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), account for some 60% of the stimulation of insulin by oral glucose, but the determinants of their secretion from the small intestine are poorly understood. Cells which release GIP (K cells) are localized to the proximal small intestine, while GLP-1 releasing cells (L cells) predominate in the distal gut. It has been suggested that a threshold rate of duodenal glucose delivery (approximately 1.8 kcal/min) needs to be exceeded for stimulation of GLP-1.
Objective: To determine whether a low intraduodenal glucose load (1 kcal/min) has the capacity to stimulate GLP-1, and if so, the characteristics of the response.
Design: Retrospective analysis of all studies in our laboratory involving healthy humans administered intraduodenal glucose at 1 kcal/min for 120 min.
Setting: Clinical research laboratory.
Participants: 27 healthy subjects (24 male; age 36+/-3 years; BMI 25.2+/-0.7 kg/m(2)).
Main Outcome Measures: Plasma GLP-1, GIP, insulin, and blood glucose concentrations, reported as mean+/-SEM.
Results: During intraduodenal glucose, plasma GLP-1 increased at 15 and 30 min (P<0.001 for both) and returned to baseline thereafter. In contrast, there were sustained increases in plasma GIP (P<0.001), insulin (P<0.001), and blood glucose (P<0.001).
Conclusion: In healthy subjects, there is early, transient stimulation of GLP-1 by glucose loads hitherto believed to be "sub-threshold". The mechanisms underlying this effect, which could be attributed to initially rapid transit to jejunal L cells, or a duodeno-jejunoileal neural or hormonal loop, remain to be determined.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.regpep.2007.09.032 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dose-related effects of calcium to enhance the effects of L-tryptophan on gut hormones and energy intake in obesity.
J Clin Endocrinol Metab
January 2025
Adelaide Medical School, University of Adelaide, Adelaide, Australia.
Context: In males of normal weight, intraduodenal administration of calcium enhances the effects of the amino acid, L-tryptophan (Trp), to suppress energy intake, associated with greater stimulation of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) secretion (key mechanisms underlying the regulation of pyloric motility and gastric emptying), but not gastrin or glucose-dependent insulinotropic polypeptide (GIP).
Objective: Given the implications for the management of obesity, the current study evaluated the effects of calcium, when administered alone and in combination with Trp, on gut hormone secretion, antropyloroduodenal motility and energy intake in males with obesity.
Methods: Fifteen males with obesity and without type 2 diabetes (mean±SD; age: 27±8 years; body mass index: 30±2 kg/m2; HbA1c: 5.
Impact of the timing of metformin administration on the plasma lactate response to intraduodenal glucose infusion in type 2 diabetes.
Diabetes Obes Metab
December 2024
Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia.
Dose-related effects of intraduodenal quinine on plasma glucose, glucoregulatory hormones and gastric emptying of a nutrient drink, and energy intake, in men with type 2 diabetes: a double-blind, randomised, crossover study.
Diabetologia
December 2024
Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Aims/hypothesis: Quinine, when administered intraduodenally to activate bitter-taste receptors, in a dose of 600 mg, stimulates glucagon-like peptide-1 (GLP-1) and insulin, slows gastric emptying and lowers postprandial glucose in healthy people, with consequent implications for the management of type 2 diabetes; the effect of quinine on energy intake is uncertain. We have investigated the dose-related effects of quinine on postprandial blood glucose levels and energy intake in people with type 2 diabetes.
Methods: Male participants with type 2 diabetes (age: 68±5 years; HbA: 49.
Intraduodenal calcium enhances the effects of L-tryptophan to stimulate gut hormone secretion and suppress energy intake in healthy males: a randomized, crossover, clinical trial.
Am J Clin Nutr
September 2024
Adelaide Medical School and Center of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia. Electronic address:
Background: In humans, intraduodenal infusion of L-tryptophan (Trp) increases plasma concentrations of gastrointestinal hormones and stimulates pyloric pressures, both key determinants of gastric emptying and associated with potent suppression of energy intake. The stimulation of gastrointestinal hormones by Trp has been shown, in preclinical studies, to be enhanced by extracellular calcium and mediated in part by the calcium-sensing receptor.
Objectives: This study aim was to determine whether intraduodenal calcium can enhance the effects of Trp to stimulate gastrointestinal hormones and pyloric pressures and, if so, whether it is associated with greater suppression of energy intake, in healthy males.
Impact of the timing of metformin administration on glycaemic and glucagon-like peptide-1 responses to intraduodenal glucose infusion in type 2 diabetes: a double-blind, randomised, placebo-controlled, crossover study.
Diabetologia
July 2024
Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
Article Synopsis
- - The study aims to understand how the timing of metformin administration affects blood sugar responses in individuals with type 2 diabetes, particularly focusing on its role in stimulating GLP-1, a hormone that helps control glucose metabolism.
- - Sixteen participants, well-managed on metformin, were tested in a controlled experiment where metformin was given at different times before a glucose infusion, measuring glucose, insulin, and GLP-1 levels throughout the process.
- - Results showed that taking metformin earlier (60 or 30 minutes before) lowered blood glucose levels more effectively and increased GLP-1 levels, while insulin responses remained consistent, indicating timing can significantly impact the effectiveness of metformin.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!