Effects of high concentration glucose on the expression of NF-kappaB, Bax and cytochrome C and apoptosis of islet cells in mice.
The roles of NF-kappaB (NF-kappaB) expression, Bax activity and cytochrome C (Cyt C) release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups: G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-kappaB expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in G1, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-kappaB expression was also increased (P<0.05), but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-kappaB expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups (P<0.05). It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-kappaB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-kappaB expression could be an effective strategy for protecting pancreatic islet cells.
Liang
Yuzhen
Y
Department of Diabetes Research Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530007, China. liangyuzhen26@yahoo.com.cn
Zhang
Muxun
M
Xia
Ning
N
Yang
Yuelian
Y
Feng
Leping
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
C494827:Bax protein, mouse; D007328:Insulin; D016328:NF-kappa B; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D005947:Glucose