8 research outputs found
In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia
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
In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia
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