[High glucose lowers insulin receptor substrate 2 expression and induces apoptosis in mouse islet cells in vitro].
OBJECTIVE
To investigate the role of insulin receptor substrate 2 (IRS2) and Bax on mouse islet cell apoptosis in the presence of high glucose in vitro.


METHODS
The pancreatic islet cells were isolated from Kunming mice and divided into 6 groups (G1-G6 groups) for a 72-h culture in the media containing different concentrations of glucose (5.6, 7.8, 11.1, 16.7, 22.2, and 27.6 mmol/L, respectively). Insulin secretion by the cells was evaluated by radioimmunoassay, and the expressions of IRS2 and Bax were detected using immunocytochemistry and immunofluorescence assay, respectively. Hoechst33342 staining was employed to observe the cell apoptosis.


RESULTS
Exposure to 5.6-11.1 mmol/L glucose resulted in increased insulin secretion and progressive elevation of IRS2 and Bax expression, whereas the cell apoptosis underwent no obvious changes. In the presence of glucose above 16.7 mmol/L, the percentages of apoptotic islet cells increased with glucose concentration, but insulin secretion and IRS2 expression decreased; Bax expression significantly increased in the presence of high-concentration glucose.


CONCLUSIONS
Prolonged exposure of mouse islet cells to high glucose induces apoptosis and impairs insulin secretion of the cells. Decreased IRS2 expression and increased Bax expression may play an important role in the glucotoxicity in mouse islet cells.
Liang
Yu-Zhen
YZ
Department of Endocrinology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. liangyuzhen26 @yahoo.com.cn
Feng
Le-Ping
LP
Xia
Ning
N
Yang
Yue-Lian
YL
Zhang
Mu-Xun
MX
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D051028:bcl-2-Associated X Protein; D005947:Glucose