Glucosamine-induced beta-cell dysfunction: a possible involvement of glucokinase or glucose-transporter type 2.
BACKGROUND
The mechanism for beta-cell dysfunction induced by glucosamine has not yet fully been investigated previously.


OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
These data imply that glucosamine impairs glucose-induced insulin release probably through the inhibition of glucose metabolism.
Yoshikawa
Hiroyasu
H
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. hiroyasi.yoshikawa@medisin.ntnu.no
Tajiri
Yuji
Y
Sako
Yasuhiro
Y
Hashimato
Toshihiko
T
Umeda
Fumio
F
Nawata
Hajime
H
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism*; D005944:Glucosamine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D006593:Hexokinase / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D010182:Pancreatic Diseases / Q000139:chemically induced; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D022722:Thermogenesis
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D001120:Arginine; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose; D005944:Glucosamine; D003981:Diazoxide