Dynamic monitoring of β-cell injury with impedance and rescue by glucagon-like peptide-1.
β-Cell injury plays an important role in the development of type 1 and type 2 diabetes. Most of the β-cell bioassays depend on labeling or endpoint assessments that might not capture the true physiology or pathology of the injury process. In the current study, we dynamically detected a broad range of pathological and pharmacological responses to four toxicants (cytokine mixture, free fatty acid mixture, streptozotocin, and hydrogen peroxide) in living β-cells (INS-1E and MIN6) by a label-free, cell-based assay system named xCELLigence, codeveloped by ACEA Biosciences and Roche Diagnostics. Our results suggest that the impedance readout is highly sensitive and provides more information than some of the conventional endpoint cytotoxicity assays for β-cell injury such as the Cell Counting Kit-8 (CCK-8) and morphology measurements. Furthermore, this system was used to evaluate the anti-injury effects of glucagon-like peptide-1 (GLP-1) and its nonpeptidic mimetic Boc5 by monitoring responses to four toxicants in two β-cell lines. This study confirms that the protective property of Boc5 on β-cells is similar to that of GLP-1.
The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Ni
N
Guan
Weiwei
W
Gao
Min
M
He
Min
M
Zheng
Xiao
X
Xu
Xiaobo
X
Wang
Ming-Wei
MW
Wang
D000818:Animals; D002460:Cell Line; D003503:Cyclobutanes / Q000494:pharmacology; D016207:Cytokines / Q000633:toxicity; D005230:Fatty Acids, Nonesterified / Q000633:toxicity; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013311:Streptozocin / Q000633:toxicity
C533559:Boc5 compound; D003503:Cyclobutanes; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D013311:Streptozocin; D052216:Glucagon-Like Peptide 1; D006861:Hydrogen Peroxide