Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and
type 2 diabetic subjects
Jerry R Greenfield, I Sadaf Farooqi, Julia M Keogh, Elana Henning, Abdella M Habib, Anthea Blackwood, Frank Reimann,
Jens J Holst, and Fiona M Gribble
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.
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 concentrations,
which peaked at 30 min in LEAN (31.9 6 5.7 pmol/L) and
OB-CON (24.3 6 2.1 pmol/L) subjects and at 45 min in OB-DIAB
subjects (19.5 6 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 6 3.4, 17.9 6 1.1, and 17.3 6 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.
Conclusion: 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.