In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia
| Autor: | Frida Leonetti, Andrea Giaccari, G. Tamburrano, Stefania Caiola, A. Buongiorno, Riccardo C. Bonadonna, D. Zorretta, L. Morviducci, P. Sbraccia |
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| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Carbohydrate metabolism Arginine beta cell function Rats Sprague-Dawley glucose toxicity chemistry.chemical_compound Insulin resistance Internal medicine Diabetes mellitus insulin resistance Insulin Secretion Internal Medicine medicine Animals Homeostasis Insulin Glycogen synthase Glucosamine biology Glycogen Glucose transporter Gluconeogenesis Glucose clamp technique medicine.disease diabetes mellitus Rats Endocrinology chemistry Liver Hyperglycemia biology.protein Glucose Clamp Technique |
| Popis: | We tested the hypothesis that glucosamine, a putative activator of glucose toxicity in vitro through acceleration of the hexosamine pathway, may determine in vivo the two key features of glucose toxicity in diabetes, namely, peripheral insulin resistance and decreased insulin secretion. Two groups of awake rats were studied either with intraarterial administration of glucosamine (5 mumol.kg-1.min-1) or saline. Insulin secretion was determined after arginine, glucose (hyperglycaemic clamp), and arginine/glucose infusions, while insulin-mediated glucose metabolism was assessed by the euglycaemic hyperinsulinaemic clamp in combination with [3-3H]-glucose infusion. Glucosamine had no effects on arginine-induced insulin secretion both at euglycaemia and hyperglycaemia, but significantly (40-50%) impaired glucose-induced insulin secretion (both first and second phases). During euglycaemic hyperinsulinaemic clamp studies, glucosamine decreased glucose uptake by approximately 30%, affecting glycolysis (estimated from 3H2O rate of appearance) and muscle glycogen synthesis (calculated from accumulation of [3H]-glucosyl units in muscle glycogen) to a similar extent. Muscle glucose 6-phosphate concentration was markedly reduced in the glucosamine-infused rats, suggesting an impairment in glucose transport/phosphorylation. Therefore, an increase in hexosamine metabolism in vivo: 1) inhibits glucose-induced insulin secretion, and 2) reduces insulin stimulation of both glycolysis and glycogen synthesis, thereby mimicking in normal rats the major alterations due to glucose toxicity in diabetes. |
| Databáze: | OpenAIRE |
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