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Candidate plasticity gene 16 mediates suppression of insulin gene expression in rat insulinoma INS-1 cells under glucotoxic conditions

Nakane, Tatsuto, Ido, Ayae, Higuchi, Takuma, Todaka, Hiroshi, Morisawa, Keiko, Nagamine, Tadashi, Fukunaga, Kensaku, Sakamoto, Shuji, Murao, Koji, Sugiyama, Yasunori
Biochemical and biophysical research communications 2019 v.512 no.2 pp. 189-195
gene expression, gene expression regulation, genes, glucose, hyperglycemia, insulin, insulin secretion, islets of Langerhans, microarray technology, models, mutants, protein kinases, quantitative polymerase chain reaction, rats, transfection
Chronic hyperglycemia causes pancreatic β-cell dysfunction, impaired insulin secretion and suppression of insulin gene expression, referred to as glucotoxicity. Insulin gene expression is regulated by several protein kinases and protein phosphatases. However, the molecular mechanisms of the suppressed insulin gene expression in glucotoxicity are not fully understood. In this study, we employed rat insulinoma INS-1 cells as a model of pancreatic glucotoxicity. In INS-1 cells, insulin gene expression is up-regulated by incubation with 11.2 mM glucose for 7 days and down-regulated by incubation with 22.4 mM glucose for the same period. To identify the protein kinases and protein phosphatases involved in the suppression of insulin gene expression, we analyzed gene expression in INS-1 cells cultured with 11.2 mM or 22.4 mM glucose for 7 days using microarray analysis and real-time PCR. The expression levels of nine protein kinases were affected by glucotoxic conditions. In particular, CPG16 expression level was increased in INS-1 cells under these conditions. Transfection of CPG16 decreased insulin promoter activity, whereas kinase-dead mutant of CPG16 did not affect this. These results suggest that CPG16 plays a role in the suppression of insulin gene expression in pancreatic β-cells under glucotoxic conditions.