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.
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Abstract|
June 01 2000
Effects of glucosamine infusion on insulin secretion and insulin action in humans.
T Monauni;
T Monauni
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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M G Zenti;
M G Zenti
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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A Cretti;
A Cretti
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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M C Daniels;
M C Daniels
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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G Targher;
G Targher
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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B Caruso;
B Caruso
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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M Caputo;
M Caputo
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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D McClain;
D McClain
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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S Del Prato;
S Del Prato
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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A Giaccari;
A Giaccari
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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M Muggeo;
M Muggeo
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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E Bonora;
E Bonora
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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R C Bonadonna
R C Bonadonna
Division of Endocrinology and Metabolic Diseases, University of Verona School of Medicine, Italy.
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Citation
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, R C Bonadonna; Effects of glucosamine infusion on insulin secretion and insulin action in humans.. Diabetes 1 June 2000; 49 (6): 926–935. https://doi.org/10.2337/diabetes.49.6.926
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