| Autor: |
Monauni, Tiziano, Zenti, Maria Grazia, Cretti, Anna, Daniels, Marc C., Targher, Giovanni, Caruso, Beatrice, Caputo, Marco, McClain, Donald, Del Prato, Stefano, Giaccari, Andrea, Muggeo, Michele, Bonora, Enzo, Bonadonna, Riccardo C., Monauni, T, Zenti, M G, Cretti, A, Daniels, M C, Targher, G, Caruso, B, Caputo, M |
| Předmět: |
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| Zdroj: |
Diabetes; Jun2000, Vol. 49 Issue 6, p926-935, 10p, 3 Diagrams, 7 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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