Potential Antidiabetic Effects of Seaweed Extracts by Upregulating Glucose Utilization and Alleviating Inflammation in C2C12 Myotubes

Seaweed is known to have various health-promoting effects. However, the mechanisms underlying seaweed’s antidiabetic effects remain unclear. We investigated the potential antidiabetic effects of seaweed water extracts and further examined their mechanism(s) using C2C12 mouse skeletal muscle cells. Briefly, we screened the physiochemical properties of seven seaweed extracts by comparing the antioxidant and α-glucosidase inhibitory effects. Among them, three seaweed extracts, Undaria pinnatifida sporophyll (UPS), Codium fragile (CF), and Gracilaria verrucosa (GV), were selected for further testing of their possible antidiabetic effects with underlying mechanisms using C2C12 myotubes. Consistent with the superior α-glucosidase inhibition of the three seaweed extracts, the extracts also enhanced glucose utilization in myotubes compared to the control. The upregulated glucose uptake by the seaweed extracts was reversed by an AMP-activated protein kinase (AMPK) inhibitor, compound C, in the UPS- and CF-treated groups. Furthermore, all three seaweed extracts significantly promoted the phosphorylation of AMPK which was completely blocked by pretreating with compound C. In addition, all three extracts reduced lipopolysaccharide-simulated TNF-α production in C2C12 cells. Our results demonstrated that all three seaweed extracts exhibited antidiabetic properties through not only the inhibition of glucose absorption but also the promotion of glucose utilization. Moreover, the regulation of inflammatory cytokine production by the extracts suggested their potential anti-inflammatory property which might play a critical role in protecting insulin sensitivity in a chronic inflammatory state. Taken together, UPS, CF, and GV are a promising source to modulate the glucose absorption and utilization in muscle cells partially via the AMPK pathway.