title: Effects of glucosamine infusion on insulin secretion and insulin action in humans.
abstract: Glucose toxicity (i.e., glucose-induced reduction in insulin secretion and action) may be mediated by an increased flux through the hexosamine-phosphate pathway. Glucosamine (GlcN) is widely used to accelerate the hexosamine pathway flux, independently of glucose. We tested the hypothesis that GlcN can affect insulin secretion and/or action in humans. In 10 healthy subjects, we sequentially performed an intravenous glucose (plus [2-3H]glucose) tolerance test (IVGTT) and a euglycemic insulin clamp during either a saline infusion or a low (1.6 micromol x min(-1) x kg(-1)) or high (5 micromol x min(-1) x kg(-1) [n = 5]) GlcN infusion. Beta-cell secretion, insulin (SI*-IVGTT), and glucose (SG*) action on glucose utilization during the IVGTT were measured according to minimal models of insulin secretion and action. Infusion of GlcN did not affect readily releasable insulin levels, glucose-stimulated insulin secretion (GSIS), or the time constant of secretion, but it increased both the glucose threshold of GSIS (delta approximately 0.5-0.8 mmol/l, P < 0.03-0.01) and plasma fasting glucose levels (delta approximately 0.3-0.5 mmol/l, P < 0.05-0.02). GlcN did not change glucose utilization or intracellular metabolism (glucose oxidation and glucose storage were measured by indirect calorimetry) during the clamp. However, high levels of GlcN caused a decrease in SI*-IVGTT (delta approximately 30%, P < 0.02) and in SG* (delta approximately 40%, P < 0.05). Thus, in humans, acute GlcN infusion recapitulates some metabolic features of human diabetes. It remains to be determined whether acceleration of the hexosamine pathway can cause insulin resistance at euglycemia in humans.
authors.affiliation: Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Monauni
authors.forename: M G
authors.initials: MG
authors.lastname: Zenti
authors.forename: A
authors.initials: A
authors.lastname: Cretti
authors.forename: M C
authors.initials: MC
authors.lastname: Daniels
authors.forename: G
authors.initials: G
authors.lastname: Targher
authors.forename: B
authors.initials: B
authors.lastname: Caruso
authors.forename: M
authors.initials: M
authors.lastname: Caputo
authors.forename: D
authors.initials: D
authors.lastname: McClain
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
authors.forename: A
authors.initials: A
authors.lastname: Giaccari
authors.forename: M
authors.initials: M
authors.lastname: Muggeo
authors.forename: E
authors.initials: E
authors.lastname: Bonora
authors.forename: R C
authors.initials: RC
authors.lastname: Bonadonna
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D005944:Glucosamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000096:biosynthesis; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose; D005944:Glucosamine