It was reported that complexes of chromium with organic ligands rather than in the form of inorganic salt generally showed low toxicities

Gastrointestinal side effects are the most common adverse events of metformin, occurring in 20,30% of patients. Therefore, an alternative antidiabetic drug with low toxicity and side effect is needed. In recent years, lots of poly-/oligosaccharides have been investigated and showed antidiabetic activities. For example, hypoglycemic activities have been demonstrated for chitooligosaccharides and its derivatives, oligosaccharides from Amorphophallus konjac and Rehmannia glutinosa. In addition, the recognized role of chromium in glucose homeostasis has lead to the investigation of chromium complexes, especially oligosaccharides-chromium complexes, for use as insulinenhancing approaches for the treatment of type 2 diabetes mellitus. Marine brown algae contain a wide variety of acidic polysaccharides such as the alginate and the fucoidans. Alginate, a water-soluble linear polymer, is an anionic heteropolysaccharide comprised of b-D-mannuronic acid and a-L-guluronic acid. Alginate oligosaccharides have attracted lots of scientific interest owning to their various biological activities, such as promoting root growth in higher plants, antitumor, and neuron protection effects. Moreover, some alginate-derived oligosaccharide and its sulfate showed a better anti-diabetes activity. In the present work, we prepared oligomannuronate and two kinds of oligomannuronate-chromium GSI-IX complexes from marine brown alga Laminaria japonica, and their insulin sensitizing effects in C2C12 skeletal muscle cells were studied. The results showed that all oligosaccharides, especially oligomannuronate-chromium complex OM2 could enhance glucose uptake in the C2C12 cells without obvious toxicity. The improvement effect might be attributed to the upregulated expression of IR mRNA and GLUT4 mRNA levels by activating both PI3K/Akt and AMPK pathways. Moreover, those oligosaccharides also distributed to the mitochondria in C2C12 cells and increased the expression of PGC-1a and CPT-1, which suggested the actions of these oligosaccharides might be associated with mitochondria. Therefore, the oligomannuronate-chromium complexes could be used as potential anti-diabetes drugs for improving the insulin sensitivity. Recently some reports indicated that marine derived polysaccharides can stimulate the insulin secretion in vitro, especially for the low molecular weight oligosaccharides around 3 kDa. In this study, we investigated the insulin sensitizing effects and mechanisms of the marine acidic oligosaccharide and its chromium complexes in skeletal muscle cells. The results showed that both the marine acidic oligosaccharide and its chromium complexes significantly enhanced insulin-stimulated glucose uptake in C2C12 cells. The oligomannuronatechromium complexes had better effect than the original oligosaccharide OM, especially for OM2 that contains 2% chromium in the oligosaccharide. Which was also verified in this experiment. Nonetheless, high-throughput short reads have proven useful in several assembly tasks.