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-H-3]glucose) tolerance test (IVGTT) and a euglycemic insulin clamp during either a saline infusion or a low (1.6 mu mol . min(-1) . kg(-1)) or high (5 mu mol . min(-1) . kg(-1) [n = 5]) GlcN infusion. beta-Cell secretion, insulin (S-I*-IVGTT), and glucose (S-G*) action on glucose utilization during the IVGTT R-ere 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 similar to 0.5-0.8 mmol/l, P < 0.03-0.01) and plasma fasting glucose levels (Delta similar to 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 n ere measured by indirect calorimetry) during the clamp. However, high levels of GlcN caused a decrease in S-I*-IVGTT (Delta similar to 30%, P < 0.02) and in S-G* (Delta similar to 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.
Effects of glucosamine infusion on insulin secretion and insulin action in humans
DEL PRATO, STEFANO;
2000-01-01
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-H-3]glucose) tolerance test (IVGTT) and a euglycemic insulin clamp during either a saline infusion or a low (1.6 mu mol . min(-1) . kg(-1)) or high (5 mu mol . min(-1) . kg(-1) [n = 5]) GlcN infusion. beta-Cell secretion, insulin (S-I*-IVGTT), and glucose (S-G*) action on glucose utilization during the IVGTT R-ere 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 similar to 0.5-0.8 mmol/l, P < 0.03-0.01) and plasma fasting glucose levels (Delta similar to 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 n ere measured by indirect calorimetry) during the clamp. However, high levels of GlcN caused a decrease in S-I*-IVGTT (Delta similar to 30%, P < 0.02) and in S-G* (Delta similar to 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
