Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
Department of Plastic and Reconstructive Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
BMC Res Notes. 2023 Sep 11;16(1):202. doi: 10.1186/s13104-023-06489-7.
Insulin secretion is regulated by ATP-sensitive potassium (K) channels in pancreatic beta-cells. Peroxisome proliferator-activated receptors (PPAR) α ligands are clinically used to treat dyslipidemia. A PPARα ligand, fenofibrate, and PPARγ ligands troglitazone and 15-deoxy-∆-prostaglandin J2 are known to close K channels and induce insulin secretion. The recently developed PPARα ligand, pemafibrate, became a new entry for treating dyslipidemia. Because pemafibrate is reported to improve glucose intolerance in mice treated with a high fat diet and a novel selective PPARα modulator, it may affect K channels or insulin secretion.
The effect of fenofibrate (100 µM) and pemafibrate (100 µM) on insulin secretion from MIN6 cells was measured by using batch incubation for 10 and 60 min in low (2 mM) and high (10 mM) glucose conditions. The application of fenofibrate for 10 min significantly increased insulin secretion in low glucose conditions. Pemafibrate failed to increase insulin secretion in all of the conditions experimented in this study. The K channel activity was measured by using whole-cell patch clamp technique. Although fenofibrate (100 µM) reduced the K channel current, the same concentration of pemafibrate had no effect. Both fenofibrate and pemafibrate had no effect on insulin mRNA expression.
胰岛素分泌受胰腺β细胞中三磷酸腺苷敏感性钾（K）通道的调节。过氧化物酶体增殖物激活受体（PPAR）α配体临床上用于治疗血脂异常。PPARα配体非诺贝特、PPARγ配体曲格列酮和 15-去氧-Δ-前列腺素 J2 已知可关闭 K 通道并诱导胰岛素分泌。最近开发的 PPARα 配体 pemafibrate 已成为治疗血脂异常的新选择。由于报道称 pemafibrate 可改善高脂肪饮食和新型选择性 PPARα调节剂治疗的小鼠的葡萄糖不耐受，因此它可能会影响 K 通道或胰岛素分泌。
通过批孵育 10 和 60 分钟，在低（2 mM）和高（10 mM）葡萄糖条件下，测量了非诺贝特（100 μM）和 pemafibrate（100 μM）对 MIN6 细胞胰岛素分泌的影响。非诺贝特孵育 10 分钟可显著增加低葡萄糖条件下的胰岛素分泌。在本研究中实验的所有条件下，pemafibrate 均未能增加胰岛素分泌。通过全细胞膜片钳技术测量 K 通道活性。虽然非诺贝特（100 μM）降低了 K 通道电流，但相同浓度的 pemafibrate 没有作用。非诺贝特和 pemafibrate 对胰岛素 mRNA 表达均没有影响。
