Antidiabetic effect of chitosan oligosaccharide (GO2KA1) is mediated via inhibition of intestinal alpha‐glucosidase and glucose transporters and PPARγ expression

Abstract

We have previously reported that administration of low molecular weight chitosan oligosaccharide (GO2KA1) significantly suppressed postprandial blood glucose rise with increased plasma adiponectin and HbA1c levels in animals and humans. However, the cellular mechanisms whereby GO2KA1 exerts antihyperglycemic effects still remain to be determined. Using intestinal Caco-2 cells and 3T3-L1 cells, here we show that GO2KA1 has dual modes of antidiabetic action by (1) inhibiting intestinal α-glucosidase as well as glucose transporters SGLT1 and GLUT2 that were distinct from the acarbose effect; (2) enhancing adipocyte differentiation, PPARγ expression and its target genes, such as FABP4, adiponectin, and GLUT4, whereas the effects were abolished by co-treatment with BADGE, a PPARγ antagonist. Moreover, GO2KA1 significantly increased glucose uptake, which was reduced in the presence of BADGE. Our data show that GO2KA1 may prevent hyperglycemia by inhibiting intestinal glucose digestion and transport and also enhance glucose uptake, at least in part, by upregulating adiponectin expression through PPARγ in adipocytes. These findings may provide potential molecular modes of action for the antidiabetic effects of chitosan oligosaccharide observed in clinical and animal studies. © 2016 BioFactors, 43(1):90-99, 2017.

Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus

“…COS can help control postprandial glucose in subjects with prediabetes 18. COS demonstrates its antidiabetic effect by inhibiting the expression of intestinal α-glucosidase, glucose transporters, and peroxisome proliferator-activated receptor γ 19. More importantly, COS can be widely used as a medicine delivery system with fewer side effects 20.…”

c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer

“…This binding is disrupted by p38 phosphorylation of PGC1α (Fan et al , ). To study this relationship in our cellular model, we measured the levels of PGC1α, phosphorylated p38, and SGLT1 (a target gene of PGC1α) (Corpe et al , ; Yu et al , ). We observed an increase in PGC1α levels and an upwards shift of the PGC1α band, probably due to post‐translational phosphorylation that occurs only in A498 and 786‐O cells.…”

Advances in the Study of Marine Products with Lipid-Lowering Properties

“…A well-known marine polysaccharide with animal origin is chitosan, which has a variety of physiological functions like lipid-lowering, drug delivery [97], anti-aging [98], immune regulation [99], hypoglycemic activities [100]. It is the most abundant renewable organic resources in the world and is a major component of crustacean shells, insect exoskeletons, and fungal cell walls.…”