膵β細胞株MIN6における脂肪毒性によるCaV1.2新規分解機構

• Published in: 日本薬理学会年会要旨集 p. 2-O-068
• Main Authors: 赤羽, 悟美, 大島, 大輔, 冨田, 太一郎, 三上, 義礼
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: Ca2+ channel; insulin; lipid metabolism; pancreatic beta cell
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_2-O-068

The voltage-dependent L-type calcium channel (L-VDCC) plays an essential role in regulating insulin secretion in pancreatic β-cell. Excessive calcium signaling due to metabolic stress has been reported to cause β-cell dysfunction and cell death. Therefore, the fine-tuning of calcium signaling is critical for the homeostatic regulation of insulin secretion. Dyslipidemia in type 2 diabetes is known to impair insulin secretion. However, the underlying mechanism has not been fully elucidated so far. In the present study, we focused on the relationship between calcium signaling and lipotoxicity to elucidate the molecular mechanism of insulin secretory failure. Protein expression of L-VDCC α1 subunit CaV1.2 in pancreatic β-cell line MIN6 was detected by flowcytometry and western blotting. When MIN6 cells were cultured in the presence of certain fatty acids, the protein expression level of CaV1.2 was significantly reduced. We confirmed that there was no change in the gene expression level of CaV1.2. The fatty acid-induced reduction of CaV1.2 protein was blunted by MG132, a proteasome inhibitor, suggesting that fatty acid promoted the degradation of CaV1.2. These results indicate that a novel lipotoxic mechanism in degrading L-VDCC CaV1.2 may be involved in dyslipidemia-induced insulin secretory failure.