High glucose-induced impairment in insulin secretion is associated with reduction in islet glucokinase in a mouse model of susceptibility to islet dysfunction

Kooptiwut, Suwattanee, Kebede, Melkam, Zraika, Sakeneh, Visinoni, Sherley, Aston-Mourney, Kathryn, Favaloro, Jenny, Tikellis, Chris, Thomas, Merlin C., Forbes, Josephine M., Cooper, Mark E., Dunlop, Marjorie, Proietto, Joseph and Andrikopoulos, Sofianos 2005, High glucose-induced impairment in insulin secretion is associated with reduction in islet glucokinase in a mouse model of susceptibility to islet dysfunction, Journal of molecular endocrinology, vol. 35, no. 1, pp. 39-48.

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Title High glucose-induced impairment in insulin secretion is associated with reduction in islet glucokinase in a mouse model of susceptibility to islet dysfunction
Author(s) Kooptiwut, Suwattanee
Kebede, Melkam
Zraika, Sakeneh
Visinoni, Sherley
Aston-Mourney, Kathryn
Favaloro, Jenny
Tikellis, Chris
Thomas, Merlin C.
Forbes, Josephine M.
Cooper, Mark E.
Dunlop, Marjorie
Proietto, Joseph
Andrikopoulos, Sofianos
Journal name Journal of molecular endocrinology
Volume number 35
Issue number 1
Start page 39
End page 48
Total pages 10
Publisher BioScientifica
Place of publication Bristol, England
Publication date 2005-08
ISSN 0952-5041
1479-6813
Keyword(s) advanced glycation end product
aminoguanidine
glucokinase
glucose
glucose transporter 2
hexokinase
insulin
Summary Type 2 diabetes is characterized by islet dysfunction resulting in hyperglycemia, which can then lead to further deterioration in islet function. A possible mechanism for hyperglycemia-induced islet dysfunction is the accumulation of advanced glycation end products (AGE). The DBA/2 mouse develops pancreatic islet dysfunction when exposed to a high glucose environment and/or obesity-induced insulin resistance. To determine the biochemical cause of dysfunction, DBA/2 and C57BL/6 control islets were incubated in 11.1 mM or 40 mM glucose in the absence or presence of the AGE inhibitor aminoguanidine (AG) for 10 days. Basal (2.8 mM glucose) insulin release was increased in both DBA/2 and C57BL/6 islets incubated with 40 mM vs 11.1 mM glucose for 10 days. Chronic exposure to hyperglycemia decreased glucose (20 mM)-stimulated insulin secretion in DBA/2 but not in C57BL/6 islets. AG significantly increased fold-induced insulin release in high glucose cultured DBA/2 mouse islets, but did not affect C57BL/6 islet function. DBA/2 islet glucokinase was significantly reduced following 40 mM glucose culture, compared with 11.1 mM glucose cultured DBA/2 islets and 40 mM glucose cultured C57BL/6 islets. Incubation of islets with AG resulted in a normalization of DBA/2 islet glucokinase levels. In conclusion, chronic high glucose-induced increases in AGE can result in islet dysfunction and this is associated with reduced glucokinase levels in a mouse model with susceptibility to islet failure.
Language eng
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2005, BioScientifica
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047516

Document type: Journal Article
Collection: School of Medicine
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