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

Pancreas. 2002 Apr;24(3):228-34. doi: 10.1097/00006676-200204000-00004.

Abstract

Introduction: The mechanism for beta-cell dysfunction induced by glucosamine has not yet fully been investigated previously.

Aim: 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.

Methodology: 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.

Results: 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.

Conclusion: These data imply that glucosamine impairs glucose-induced insulin release probably through the inhibition of glucose metabolism.

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Cells, Cultured
  • Diazoxide / pharmacology
  • Female
  • Gene Expression
  • Glucokinase / genetics
  • Glucokinase / metabolism*
  • Glucosamine / pharmacology*
  • Glucose / pharmacology
  • Glucose Transporter Type 2
  • Hexokinase / genetics
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / physiology*
  • Oxidative Stress
  • Pancreatic Diseases / chemically induced
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Radioimmunoassay
  • Rats
  • Rats, Wistar
  • Thermogenesis

Substances

  • Glucose Transporter Type 2
  • Insulin
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • Arginine
  • Hexokinase
  • Glucokinase
  • Glucose
  • Glucosamine
  • Diazoxide