title: Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects.
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 concentrations in vivo and, if so, whether this is associated with an increase in plasma insulin.
  
  
  METHODS
  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 concentrations, 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 concentrations increased in all study groups after glutamine ingestion, with peak concentrations 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 concentrations but less effectively than glucose. Consistent with the increases in GLP-1 and GIP, glutamine significantly increased circulating plasma insulin concentrations. Glutamine stimulated glucagon secretion in all 3 study groups.
  
  
  CONCLUSIONS
  Glutamine effectively increases circulating GLP-1, GIP, and insulin concentrations in vivo and may represent a novel therapeutic approach to stimulating insulin secretion in obesity and type 2 diabetes.
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Greenfield
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: Julia M
authors.initials: JM
authors.lastname: Keogh
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: Elana
authors.initials: E
authors.lastname: Henning
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: Abdella M
authors.initials: AM
authors.lastname: Habib
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: Anthea
authors.initials: A
authors.lastname: Blackwood
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK (JRG, ISF, JMK, EH, AMH, AB, FR, FMG), and the Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark (JJH).
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D005951:Glucose Tolerance Test; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009765:Obesity / Q000097:blood; D013851:Thinness / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005973:Glutamine; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon