Han Taewon, Ko Eun, Kim Minji, Choi Moonsung, Lee Changho, Kim In-Ho, Shin Sooim, Um Min Young
Division of Functional Food Research, Korea Food Research Institute, Wanju 55365, Korea.
Department of Food and Biotechnology, Korea University, Sejong City 30019, Korea.
Antioxidants (Basel). 2021 Jun 3;10(6):901. doi: 10.3390/antiox10060901.
Type 2 diabetes mellitus is characterized by insulin resistance and pancreatic beta (β)-cell dysfunction. Accumulating evidence suggests that mitochondrial dysfunction may cause insulin resistance in peripheral tissues. As commercial hypoglycemic drugs have side effects, it is necessary to develop safe and effective natural compound-based hypoglycemic treatments. This study aimed to investigate the hypoglycemic effects of Mori Ramulus ethanol extract (ME) in a high-fat diet (HFD)-induced diabetes mouse model to decipher the underlying mechanisms focusing on apoptosis and mitochondrial function. ME significantly decreased tunicamycin-induced apoptotic cell death and increased insulin secretion following glucose stimulation in NIT-1 pancreatic β-cells. Tunicamycin-exposed NIT-1 pancreatic β-cells showed elevated reactive oxygen species levels and reduced mitochondrial membrane potential, which were reversed by ME treatment. ME inhibited the tunicamycin-induced apoptosis cascade in tunicamycin-exposed NIT-1 pancreatic β-cells. In HFD diabetic mice, the serum-free fatty acid and insulin levels decreased following a 15-week ME administration. Glucose and insulin tolerance tests showed that ME improved insulin sensitivity. Moreover, ME ameliorated pancreatic β-cell mass loss in diabetic mice. Finally, ME-treated HFD-fed mice showed improved hepatic mitochondrial function resulting in insulin sensitivity in target tissues. Thus, ME provides protection against pancreatic β-cell apoptosis and prevents insulin resistance by improving mitochondrial function.
2型糖尿病的特征是胰岛素抵抗和胰腺β细胞功能障碍。越来越多的证据表明，线粒体功能障碍可能导致外周组织中的胰岛素抵抗。由于商业降糖药物有副作用，因此有必要开发基于安全有效天然化合物的降糖疗法。本研究旨在研究桑枝乙醇提取物（ME）在高脂饮食（HFD）诱导的糖尿病小鼠模型中的降糖作用，以阐明其聚焦于细胞凋亡和线粒体功能的潜在机制。ME显著降低衣霉素诱导的NIT-1胰腺β细胞凋亡性细胞死亡，并增加葡萄糖刺激后的胰岛素分泌。暴露于衣霉素的NIT-1胰腺β细胞显示活性氧水平升高和线粒体膜电位降低，而ME处理可使其逆转。ME抑制了暴露于衣霉素的NIT-1胰腺β细胞中衣霉素诱导的凋亡级联反应。在HFD糖尿病小鼠中，给予ME 15周后，血清游离脂肪酸和胰岛素水平降低。葡萄糖和胰岛素耐量试验表明，ME改善了胰岛素敏感性。此外，ME改善了糖尿病小鼠胰腺β细胞质量的损失。最后，给予ME处理的HFD喂养小鼠显示肝脏线粒体功能改善，从而导致靶组织中的胰岛素敏感性提高。因此，ME可保护胰腺β细胞免受凋亡，并通过改善线粒体功能预防胰岛素抵抗。
