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Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects^1,2,3,4

¹ From the Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom (JRG, ISF, JMK, EH, AMH, AB, FR, and FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark (JJH).

² JRG and ISF contributed equally to this work.

³ Supported by the National Health & Medical Research Council of Australia, The Royal Australasian College of Physicians and St. Vincent's Clinic Foundation, Sydney, Australia (JRG), and the Wellcome Trust (ISF and FMG).

⁴ Reprints not available. Address correspondence to FM Gribble, Cambridge Institute for Medical Research and Department of Clinical Biochemistry, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, United Kingdom. E-mail: fmg23{at}cam.ac.uk.

ABSTRACT

Background: Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in meal-related insulin secretion. We previously demonstrated that glutamine is a potent stimulus of GLP-1 secretion in vitro.

Objective: Our objective was to determine whether glutamine increases circulating GLP-1 and GIP levels in vivo and, if so, whether this is associated with an increase in plasma insulin.

Design: We recruited 8 healthy normal-weight volunteers (LEAN), 8 obese individuals with type 2 diabetes or impaired glucose tolerance (OB-DIAB) and 8 obese nondiabetic control subjects (OB-CON). Oral glucose (75 g), glutamine (30 g), and water were administered on 3 separate days in random order, and plasma concentrations of GLP-1, GIP, insulin, glucagon, and glucose were measured over 120 min.

Results: Oral glucose led to increases in circulating GLP-1 levels, which peaked at 30 min in LEAN (31.9 ± 5.7 pmol/L) and OB-CON (24.3 ± 2.1 pmol/L) subjects and at 45 min in OB-DIAB subjects (19.5 ± 1.8 pmol/L). Circulating GLP-1 levels increased in all study groups after glutamine ingestion, with peak levels at 30 min of 22.5 ± 3.4, 17.9 ± 1.1, and 17.3 ± 3.4 pmol/L in LEAN, OB-CON, and OB-DIAB subjects, respectively. Glutamine also increased plasma GIP levels but less effectively than glucose. Consistent with the increases in GLP-1 and GIP, glutamine significantly increased circulating plasma insulin levels. Glutamine stimulated glucagon secretion in all 3 study groups.

Conclusion: Glutamine effectively increases circulating GLP-1, GIP, and insulin levels in vivo and may represent a novel therapeutic approach to stimulating insulin secretion in obesity and type 2 diabetes.

Received for publication May 2, 2008. Accepted for publication September 28, 2008.