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Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery
- Source :
- American Journal of Physiology-Endocrinology and Metabolism. 310:E505-E514
- Publication Year :
- 2016
- Publisher :
- American Physiological Society, 2016.
-
Abstract
- Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and β-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9–39) (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose-tolerant patients were studied after RYGB in a randomized, placebo-controlled, 4-day crossover study with standard mixed-meal tests and concurrent administration of placebo, oral sitagliptin, Ex-9 infusion, or combined Ex-9-sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated β-cell function, and aggravated postprandial hyperglucagonemia compared with placebo, whereas sitagliptin had no effect despite two- to threefold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or β-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB.
- Subjects :
- Adult
Blood Glucose
Male
0301 basic medicine
endocrine system
medicine.medical_specialty
Physiology
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Gastric Bypass
Enzyme-Linked Immunosorbent Assay
030209 endocrinology & metabolism
Gastric Inhibitory Polypeptide
Glucagon
Glucagon-Like Peptide-1 Receptor
Sitagliptin Phosphate
03 medical and health sciences
0302 clinical medicine
Gastric inhibitory polypeptide
Glucagon-Like Peptide 1
Physiology (medical)
Internal medicine
medicine
Humans
Hypoglycemic Agents
Single-Blind Method
Obesity
Glucose tolerance test
Cross-Over Studies
C-Peptide
medicine.diagnostic_test
business.industry
Insulin
digestive, oral, and skin physiology
Glucagon secretion
Glucose Tolerance Test
Postprandial Period
Peptide Fragments
030104 developmental biology
Endocrinology
Postprandial
Sitagliptin
Linear Models
Female
business
hormones, hormone substitutes, and hormone antagonists
medicine.drug
Subjects
Details
- ISSN :
- 15221555 and 01931849
- Volume :
- 310
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Endocrinology and Metabolism
- Accession number :
- edsair.doi.dedup.....ecb44f4d9302db52c3987b8cade9b066