Journal Article

Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass

Hansen, Dorte L., Holst, Jens J., Dirksen, Carsten, Jørgensen, Nils B., Jacobsen, Siv H., Worm, Dorte, Kristiansen, Viggo B., Naver, Lars S., Bojsen-Møller, Kirstine N., Madsbad, Sten

2013

Overview

Aims/hypothesis Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones, including GLP-1, is altered. Methods Eleven severely obese glucose-tolerant individuals underwent three hyperglycaemic clamps with arginine bolus and co-infusion of either GLP-1, glucose-dependent insulinotropic polypeptide (GIP) or saline before, and at 1 week and 3 months after RYGB. In addition, an OGTT was performed before and 3 months after surgery. Results After RYGB, insulin sensitivity improved at 1 week and 3 months, while insulin stimulation and glucagon suppression in response to the clamp with saline co-infusion were largely unaltered. The influence of i.v. GLP-1 and GIP on insulin and glucagon secretion was also unchanged postoperatively. In response to the postoperative OGTT at 3 months, insulin and GLP-1, but not GIP, secretion increased. Furthermore, the glucose profile during the OGTT was altered, with a substantial reduction in 2 h plasma glucose and a paradoxical hypersecretion of glucagon. Conclusions/interpretation After RYGB, insulin hypersecretion is linked to the oral, but not the i.v., route of administration and is associated with exaggerated release and preserved insulinotropic action of GLP-1, while both the secretion and action of GIP are unchanged. The results highlight the importance of increased GLP-1 secretion for improving postoperative glucose metabolism. Trial registration ClinicalTrials.gov NCT01559779.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Adult / Biological and medical sciences / Blood Glucose - metabolism / Diabetes / Diabetes. Impaired glucose tolerance / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Gastric Bypass / Gastric Inhibitory Polypeptide - metabolism / Gastrointestinal surgery / Glucagon / Glucagon - metabolism / Glucagon-Like Peptide 1 - metabolism / Glucose / Glucose Clamp Technique - methods / Glucose Tolerance Test / Hormones / Human Physiology / Humans / Hyperglycemia - metabolism / Hypotheses / Insulin - metabolism / Insulin Resistance / Insulin Secretion / Internal Medicine / Male / Medical sciences / Medicine / Medicine & Public Health / Metabolic Diseases / Metabolism / Obesity / Obesity, Morbid - metabolism / Obesity, Morbid - physiopathology / Obesity, Morbid - surgery / Pancreas - metabolism / Peptide Fragments - metabolism / Polypeptides / Postprandial Period / Treatment Outcome / Weight control