title: 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.
authors.affiliation: Department of Nutrition, University of Massachusetts, Amherst, MA, USA.
authors.forename: Seok-Yeong
authors.initials: SY
authors.lastname: Yu
authors.affiliation: Department of Food and Nutrition, Hannam University, Daejeon, Korea.
authors.forename: Young-In
authors.initials: YI
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Technology, Chung-Ang University, Kyeonggi-Do, Korea.
authors.forename: Chan
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Food Science, Framingham State University, MA, USA.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Apostolidis
authors.affiliation: Department of Nutrition, University of Massachusetts, Amherst, MA, USA.
authors.forename: Young-Cheul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; C000614667:GO2KA1; D051275:Glucose Transporter Type 4; D065089:Glycoside Hydrolase Inhibitors; D047495:PPAR gamma; C495693:Slc2a4 protein, mouse; D048271:Chitosan; D000520:alpha-Glucosidases; D005947:Glucose
keywords: Caco-2 cell; GLUT4; PPARγ; adipocyte; diabetes; α-glucosidase