Department of Pharmacology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Department of Pediatric Endocrinology, The First Clinical Hospital Affiliated to Jilin University, Changchun 130021, China.
Int J Biol Sci. 2019 Jun 2;15(7):1533-1545. doi: 10.7150/ijbs.32020. eCollection 2019.
: Berberine (BBR) improves beta-cell function in Type 2 diabetes (T2D) because of its anti-apoptotic activity, and our laboratory developed a new preparation named Huang-Gui Solid Dispersion (HGSD) to improve the oral bioavailability of BBR. However, the mechanism by which BBR inhibits beta-cell apoptosis is unclear. We hypothesized that the Group VIA Ca-Independent Phospholipase A (iPLAβ)/Cardiolipin(CL)/Opa1 signaling pathway could exert a protective role in T2D by regulating beta-cell apoptosis and that HGSD could inhibit β-cell apoptosis through iPLAβ/CL/Opa1 upregulation. : We examined how iPLAβ and BBR regulated apoptosis and insulin secretion through CL/Opa1 and . In studies, we developed Palmitate(PA)-induced apoptotic cell death model in mouse insulinoma cells (MIN6). iPLAβ overexpression and silencing technology were used to examine how the iPLAβ/CL/Opa1 interaction may play an important role in BBR treatment. In studies, db/db mice were used as a diabetic animal model. The pancreatic islet function and morphology, beta-cell apoptosis and mitochondrial injury were examined to explore the effects of HGSD. The expression of iPLAβ/CL/Opa1 was measured to explore whether the signaling pathway was damaged in T2D and was involved in HGSD treatment. : The overexpression of iPLAβ and BBR treatment significantly attenuated Palmitate- induced mitochondrial injury and apoptotic death compared with Palmitate-treated MIN6 cell. In addition, iPLAβ silencing could simultaneously partly abolish the anti-apoptotic effect of BBR and decrease CL/Opa1 signaling in MIN6 cells. Moreover, HGSD treatment significantly decreased beta-cell apoptosis and resulted in the upregulation of iPLAβ/CL/Opa1 compared to those of the db/db mice. : The results indicated that the regulation of iPLAβ/CL/Opa1 by HGSD may prevent beta-cell apoptosis and may improve islet beta-cell function in Type 2 diabetic mice and in palmitate-treated MIN6 cells.
: 小檗碱（BBR）通过其抗细胞凋亡作用改善 2 型糖尿病（T2D）中的β细胞功能，我们的实验室开发了一种名为黄桂固体分散体（HGSD）的新制剂，以提高 BBR 的口服生物利用度。然而，BBR 抑制β细胞凋亡的机制尚不清楚。我们假设 Group VIA Ca 非依赖性磷脂酶 A（iPLAβ）/心磷脂（CL）/Opa1 信号通路可以通过调节β细胞凋亡在 T2D 中发挥保护作用，并且 HGSD 可以通过 iPLAβ/CL/Opa1 的上调来抑制β细胞凋亡。 : 我们研究了 iPLAβ 和 BBR 如何通过 CL/Opa1 调节细胞凋亡和胰岛素分泌。在 研究中，我们在小鼠胰岛素瘤细胞（MIN6）中建立了棕榈酸（PA）诱导的凋亡细胞死亡模型。使用 iPLAβ 过表达和沉默技术来研究 iPLAβ/CL/Opa1 相互作用如何在 BBR 治疗中发挥重要作用。在 研究中，我们使用 db/db 小鼠作为糖尿病动物模型。检查了 HGSD 对胰岛功能和形态、β细胞凋亡和线粒体损伤的影响。测量了 iPLAβ/CL/Opa1 的表达，以探讨该信号通路在 T2D 中是否受损并参与 HGSD 治疗。 : 与棕榈酸盐处理的 MIN6 细胞相比，iPLAβ 的过表达和 BBR 处理显着减轻了棕榈酸诱导的线粒体损伤和凋亡死亡。此外，iPLAβ 沉默可以同时部分消除 BBR 的抗凋亡作用，并降低 MIN6 细胞中的 CL/Opa1 信号。此外，与 db/db 小鼠相比，HGSD 处理显着降低了β细胞凋亡，并导致 iPLAβ/CL/Opa1 的上调。 : 结果表明，HGSD 对 iPLAβ/CL/Opa1 的调节可能防止β细胞凋亡，并可能改善 2 型糖尿病小鼠和棕榈酸处理的 MIN6 细胞中的胰岛β细胞功能。
