Glucosamine-induced beta-cell dysfunction: a possible involvement of glucokinase or glucose-transporter type 2.

Abstract

The mechanism for beta-cell dysfunction induced by glucosamine has not yet fully been investigated previously. To investigate the effects of glucosamine on insulin release or gene expression related to glucose metabolism in rat islets cultured with glucosamine for 24 hours. After islets were cultured with glucosamine or diazoxide, we measured glucose- or arginine-induced insulin release by using radioimmunoassay (RIA) and gene expressions by semiquantitative polymerase/chain reaction. Coculture with glucosamine inhibited 27 mmol/L glucose-induced insulin release with no effects on 20 mmol/L arginine-induced insulin release. Coculture with diazoxide did not restore the impaired glucose-induced insulin release. In glucosamine-cultured islets, glucose-transporter type 2 or glucokinase mRNA expression decreased, whereas hexokinase mRNA increased. Phosphofructokinase-A, pyruvate dehydrogenase E1alpha, or pyruvate carboxylase mRNA was not affected by the addition of glucosamine. Pancreatic and duodenal homeobox-1, preproinsulin, or p21 (induced by oxidative stress) mRNA expression did not change, whereas uncoupling protein 2 mRNA, which plays an important role in thermogenesis, decreased in glucosamine-cultured islets. These data imply that glucosamine impairs glucose-induced insulin release probably through the inhibition of glucose metabolism.