Anti-diabetic activities of agaropectin-derived oligosaccharides from Gloiopeltis furcata via regulation of mitochondrial function

The aim of the present study was to investigate whether agaropectin-derived oligosaccharides from Gloiopeltis furcata (SAOs) exert an anti-diabetic effect in sodium palmitate (PA)-induced insulin resistant HepG2 cells. We found that SAOs were co-localized with mitochondria and regulated mitochondrial function. SAOs reduced respiratory chain activities, which led to reduced respiratory oxygen consumption and increased the cellular ADP/ATP ratio in a certain degree of dose-dependent manner. Thus, SAOs alleviated the oxidative stress state in PA-treated cells and, moreover, concurrently regulated the ROS-JNK-IRS-1 pathway. As a result, SAOs enhanced insulin sensitivity and glucose metabolism by activating the IRS-1-AKT-GSK-3 beta-GS pathway. Additionally, SAOs activated AMPK through both PKA-LKB1 and mitochondrial-regulated energy metabolism pathways. Therefore, SAOs decreased accumulation of lipids and improved lipid metabolism via regulating HMGCR, ACC and SREBP-1 proteins in HepG2 cells. Taken together, we conclude that SAOs could significantly ameliorate diabetic states in vitro via regulating mitochondria and their downstream signaling pathways.