MD, PhD, Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Endocrinology. 2013 Nov;154(11):4058-67. doi: 10.1210/en.2013-1351. Epub 2013 Aug 22.
Male hypogonadism associates with type 2 diabetes, and T can protect pancreatic β-cells from glucotoxicity. However, the protective mechanism is still unclear. This study thus aims to examine the antiapoptotic mechanism of T in pancreatic β cells cultured in high-glucose medium. T (0.0005-2 μg/mL) was added to INS-1 cells cultured in basal glucose or high-glucose media. Then cellular apoptosis, oxidative stress, and cell viability were measured. Endoplasmic reticulum (ER) stress markers and sensors and the antiapoptotic protein (B-cell lymphoma 2) were investigated by real-time PCR and Western blot analysis. ER stress markers were also measured in male mouse pancreatic islet cultured in similar conditions. T (0.05 and 0.5 μg/mL) did not have any effect on apoptosis and viability of INS-1 cells cultured in basal glucose medium, but it could reduce apoptosis and increase viability of INS-1 cells cultured in high-glucose medium. The protective effect of T is diminished by androgen receptor inhibitor. T (0.05 μg/mL) could significantly reduce nitrotyrosine levels, mRNA, and protein levels of the ER stress markers and sensor those that were induced when INS-1 cells were cultured in high-glucose medium. It could also significantly increase the survival proteins, sarco/endoplasmic reticulum Ca(2+) ATPase-2, and B-cell lymphoma 2 in INS-1 cells cultured in the same conditions. Similarly, it could reduce ER stress markers and increase sarco/endoplasmic reticulum Ca(2+) ATPase protein levels in male mouse pancreatic islets cultured in high-glucose medium. T can protect against male pancreatic β-cell apoptosis from glucotoxicity via the reduction of both oxidative stress and ER stress.
男性性腺功能减退症与 2 型糖尿病有关，而 T 可以保护胰岛β细胞免受糖毒性。然而，其保护机制尚不清楚。因此，本研究旨在研究 T 在高糖培养基中培养的胰岛β细胞中的抗凋亡机制。将 T（0.0005-2μg/mL）添加到基础葡萄糖或高葡萄糖培养基中培养的 INS-1 细胞中。然后测量细胞凋亡、氧化应激和细胞活力。通过实时 PCR 和 Western blot 分析研究内质网（ER）应激标志物和传感器以及抗凋亡蛋白（B 细胞淋巴瘤 2）。还在类似条件下培养的雄性小鼠胰岛中测量 ER 应激标志物。T（0.05 和 0.5μg/mL）对在基础葡萄糖培养基中培养的 INS-1 细胞的凋亡和活力没有任何影响，但可以降低在高葡萄糖培养基中培养的 INS-1 细胞的凋亡并增加其活力。雄激素受体抑制剂可降低 T 的保护作用。T（0.05μg/mL）可显著降低 INS-1 细胞在高葡萄糖培养基中培养时诱导的硝基酪氨酸水平、ER 应激标志物和传感器的 mRNA 和蛋白水平。它还可以显著增加在相同条件下培养的 INS-1 细胞中的存活蛋白，肌浆/内质网 Ca2+ATP 酶-2 和 B 细胞淋巴瘤 2。同样，它可以降低雄性小鼠胰岛在高葡萄糖培养基中培养时的 ER 应激标志物并增加肌浆/内质网 Ca2+ATP 酶蛋白水平。T 可以通过减少氧化应激和内质网应激来保护男性胰岛β细胞免受糖毒性引起的凋亡。
