Effects of glucosamine infusion on insulin secretion and insulin action in humans

• Published in: Diabetes (New York, N.Y.) Vol. 49; no. 6; pp. 926 - 935
• Main Authors: MONAUNI, T, ZENTI, M. G, MUGGEO, M, BONORA, E, BONADONNA, R. C, CRETTI, A, DANIELS, M. C, TARGHER, G, CARUSO, B, CAPUTO, M, MCCLAIN, D, DEL PRATO, S, GIACCARI, A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2000
• Subjects: Adult; Biological and medical sciences; Biological transport; Blood Glucose - analysis; C-Peptide - blood; Endocrine pancreas; Fundamental and applied biological sciences. Psychology; Glucosamine - administration & dosage; Glucosamine - blood; Glucosamine - pharmacology; Glucose - biosynthesis; Glucose Clamp Technique; Glucose metabolism; Glucose Tolerance Test; Hormones. Régulation; Humans; Hyperglycemia; Infusions, Intravenous; Insulin; Insulin - blood; Insulin - metabolism; Insulin - physiology; Insulin Secretion; Islets of Langerhans - metabolism; Male; Osmolar Concentration; Physiological aspects; Physiological transport; Reference Values; Vertebrates: endocrinology; Italy; Human; Pancreatic hormone; Glucosamine; Hexosamine; Metabolic pathway; Insulin; Biological activity; Endocrine secretion
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.49.6.926

Effects of glucosamine infusion on insulin secretion and insulin action in humans. T Monauni , M G Zenti , A Cretti , M C Daniels , G Targher , B Caruso , M Caputo , D McClain , S Del Prato , A Giaccari , M Muggeo , E Bonora and R C Bonadonna Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy. 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.