Department of Dermatology, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Ophthalmology, Nanjing University of Chinese Medicine, Nanjing, China.
Cell Biochem Funct. 2020 Jul;38(5):567-573. doi: 10.1002/cbf.3504. Epub 2020 Feb 20.
Obesity and insulin resistance affect metabolic reactions, but their ensuing contributions to macrophage metabolism remain insufficiently understood. We investigated the contributions of berberine and metformin combination to the inhibition of sebocyte apoptosis in high-fat diet-induced diabetic hamsters and an insulin-treated human cell line. Golden hamsters were fed a high-glucose high-fat diet and administered a 6-week treatment with a combination of metformin and two concentrations of berberine (100 or 50 mg·kg ). Body weights of treated hamsters were remarkably reduced compared with those of controls. Histological examination indicated that berberine repressed liver fat accumulation. Moreover, insulin and glucose concentrations were noticeably decreased by the combination treatments. In glucose tolerance tests, hamsters receiving berberine displayed higher tolerance to glucose, compared with the control group. Sebocytes isolated from high-fat diet-induced diabetic hamsters and insulin-treated human sebocytes displayed elevated cell death rates, which were attenuated by berberine and metformin treatments. Further studies showed that the effects of metformin and berberine on cellular apoptosis were mediated via the Bik pathway. Thus, berberine may effectively decrease circulating glucose levels, ameliorate insulin resistance, reduce body weight, and attenuate sebocyte apoptosis in diabetic hamsters, potentially decreasing vulnerability to the cardiovascular complications of diabetes. SIGNIFICANCE OF THE STUDY: The present data indicate that insulin stimulates changes in the expression levels of cell death-associated proteins, which participate in sebaceous gland diseases during obesity or diabetes. The anti-apoptotic effects of BBR and MET in sebaceous gland cells are regulated partially by Bik expression. To the best of our knowledge, this study is the first to suggest cell death counteracting effects of BBR in hamster and human sebocytes as well as to propose BBR as an innovative therapeutic agent for insulin-related sebaceous gland diseases, including acne.
肥胖和胰岛素抵抗会影响代谢反应，但它们对巨噬细胞代谢的后续影响仍了解不足。我们研究了黄连素和二甲双胍联合使用对高脂肪饮食诱导的糖尿病金黄地鼠和胰岛素处理的人细胞系中皮脂细胞凋亡的抑制作用。金黄地鼠喂食高葡萄糖高脂肪饮食，并接受二甲双胍和两种浓度黄连素（100 或 50mg·kg）联合治疗 6 周。与对照组相比，接受治疗的金黄地鼠体重明显减轻。组织学检查表明黄连素抑制了肝脏脂肪堆积。此外，胰岛素和葡萄糖浓度也明显降低。在葡萄糖耐量试验中，与对照组相比，接受黄连素治疗的金黄地鼠对葡萄糖的耐受力更高。从高脂肪饮食诱导的糖尿病金黄地鼠和胰岛素处理的人皮脂细胞中分离出的皮脂细胞显示细胞死亡率升高，而黄连素和二甲双胍处理可减弱这种升高。进一步的研究表明，二甲双胍和黄连素对细胞凋亡的作用是通过 Bik 途径介导的。因此，黄连素可能通过降低循环血糖水平、改善胰岛素抵抗、减轻体重和减轻糖尿病金黄地鼠的皮脂细胞凋亡，从而降低糖尿病心血管并发症的易感性。研究的意义：本研究数据表明，胰岛素刺激与细胞死亡相关的蛋白表达水平的变化，这些变化参与肥胖或糖尿病期间的皮脂腺疾病。BBR 和 MET 在皮脂腺细胞中的抗凋亡作用部分受 Bik 表达的调节。据我们所知，这项研究首次提出 BBR 在金黄地鼠和人皮脂细胞中具有拮抗细胞死亡的作用，并提出 BBR 是一种用于治疗与胰岛素相关的皮脂腺疾病（包括痤疮）的创新治疗剂。
