The cytotoxic role of intermittent high glucose on apoptosis and cell viability in pancreatic beta cells.
OBJECTIVE
Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms.


METHODS
Cells were treated with normal glucose (5.5 mmol/L), constant high glucose (CHG) (25 mmol/L), and IHG (rotation per 24 h in 11.1 or 25 mmol/L) for 7 days. Reactive oxygen species (ROS), xanthine oxidase (XOD) level, apoptosis, cell viability, cell cycle, and expression of cyclinD1, p21, p27, and Skp2 were determined.


RESULTS
We found that IHG induced more significant apoptosis than CHG and normal glucose; intracellular ROS and XOD levels were more markedly increased in cells exposed to IHG. Cells treated with IHG showed significant decreased cell viability and increased cell proportion in G0/G1 phase. Cell cycle related proteins such as cyclinD1 and Skp2 were decreased significantly, but expressions of p27 and p21 were increased markedly.


CONCLUSIONS
This study suggested that IHG plays a more toxic effect including both apoptosis-inducing and antiproliferative effects on INS-1 cells. Excessive activation of cellular stress and regulation of cyclins might be potential mechanism of impairment in INS-1 cells induced by IHG.
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Zhen
Z
Zhang
Department of Endocrinology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen 518052, China.
Jing
J
Li
Department of Nephrology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China.
Lei
L
Yang
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Rongping
R
Chen
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Rui
R
Yang
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Hua
H
Zhang
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Dehong
D
Cai
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Hong
H
Chen
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000819:agonists / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000819:agonists / Q000378:metabolism*; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D050417:Insulin-Secreting Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D044786:S-Phase Kinase-Associated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D014969:Xanthine Oxidase / Q000737:chemistry / Q000378:metabolism
C530106:Ccnd1 protein, rat; C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017382:Reactive Oxygen Species; D044786:S-Phase Kinase-Associated Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D014969:Xanthine Oxidase; D005947:Glucose