title: Rice bran protein hydrolysates prevented interleukin-6- and high glucose-induced insulin resistance in HepG2 cells.
abstract: Rice bran, which is a byproduct of rice milling process, contains various nutrients and biologically active compounds. Rice bran protein hydrolysates have various pharmacological activities such as antidiabetic and antidyslipidemic effects. However, there are limited studies about the mechanisms of rice bran protein hydrolysates (RBP) on insulin resistance and lipid metabolism. RBP used in this study were prepared from Thai Jasmine rice. When HepG2 cells were treated with IL-6, the IRS-1 expression and Akt phosphorylation were suppressed. This effect of IL-6 was prevented by RBP in association with inhibition of STAT3 phosphorylation and SOCS3 expression. RBP could increase the phospho-AMPK levels and inhibit IL-6- or high glucose-induced suppression of AMPK and Akt activation. High glucose-induced dysregulation of the expression of lipogenic genes, including SREBP-1c, FASN and CPT-1, was normalized by RBP treatment. Moreover, impaired glucose utilization in insulin resistant HepG2 cells was significantly alleviated by concurrent treatment with RBP. Our results suggested that RBP suppresses inflammatory cytokine signaling and activates AMPK, and thereby these effects may underlie the insulin sensitizing effect.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Thailand. veerapol@kku.ac.th.
authors.forename: Kampeebhorn
authors.initials: K
authors.lastname: Boonloh
authors.forename: Upa
authors.initials: U
authors.lastname: Kukongviriyapan
authors.forename: Patchareewan
authors.initials: P
authors.lastname: Pannangpetch
authors.forename: Bunkerd
authors.initials: B
authors.lastname: Kongyingyoes
authors.forename: Laddawan
authors.initials: L
authors.lastname: Senggunprai
authors.forename: Auemduan
authors.initials: A
authors.lastname: Prawan
authors.forename: Supawan
authors.initials: S
authors.lastname: Thawornchinsombut
authors.forename: Veerapol
authors.initials: V
authors.lastname: Kukongviriyapan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D050171:Dyslipidemias / Q000188:drug therapy; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000009:adverse effects*; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D012275:Oryza / Q000737:chemistry*; D010766:Phosphorylation; D011492:Protein Hydrolysates / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; D011492:Protein Hydrolysates; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose