Catalpol ameliorates hepatic insulin resistance in type 2 diabetes through acting on AMPK/NOX4/PI3K/AKT pathway. (April 2018)

• Record Type: Journal Article
• Authors: Yan, Jiting; Wang, Changyuan; Jin, Yue; Meng, Qiang; Liu, Qi; Liu, Zhihao; Liu, Kexin; Sun, Huijun
• Is Part Of: Pharmacological research. Volume 130(2018)
• Page Start: 466
• Page End: 480
• Publication Date: 2018-04
• Subjects: HFD high fat-diet -- STZ streptozotocin -- IRS-1 insulin receptor substrate-1 -- PI3K phosphatidylinositol 3-kinase -- PEPCK phosphoenolpyruvate carboxykinase -- G6pase glucose 6-phosphatase -- FOXO1 forkhead box O1 -- GSK3β glycogen synthase kinase-3β -- GS glycogen synthase -- NOX4 NADPH oxidase type 4 -- AMPK AMP-activated protein kinase -- ROS reactive oxygen species -- SOD superoxide dismutase -- GSH glutathione -- MDA malondialdehyde -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- OGTT oral glucose tolerance tests -- ITT insulin tolerance tests -- siRNA short interfering RNA; Type 2 diabetes -- Catalpol -- Insulin resistance -- AMPK -- NOX4; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2017.12.026
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Type 2 diabetes is characterized by insulin resistance in target tissues and hyperglycemia. Catalpol is a natural product isolated from the root of Rehmannia glutinosa, which has been reported to produce the effect of anti-diabetes in recent reports. The goal of the current study is to investigate the therapeutic effects of catalpol on hepatic insulin resistance in type 2 diabetes and elucidate the underlying cellular mechanisms. Type 2 diabetes in vivo was induced by combined high-fat diet (HFD) and streptozotocin (STZ) injection in C57BL/6J mice. Insulin resistance in vitro was induced by glucosamine administration in HepG2 cells. Catalpol exhibited the effects decreasing hepatic gluconeogenesis and increasing hepatic glycogen synthesis both in vivo and in vitro . Additionally, catalpol improved hepatic NADPH oxidase type 4 (NOX4)-mediated oxidative stress and activated hepatic AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathway in vivo and in vitro . The effects of catalpol on preventing gluconeogenesis and increasing glycogen synthesis in glucosamine-induced HepG2 cells were prevented by pretreatment with LY294002, the inhibitor of PI3K. Furthermore, the effect of catalpol on depriving glucosamine-induced insulin resistance was prevented by knockdown of NOX4 or AMPK with short interfering RNA (siRNA) in HepG2 cells. Moreover, the suppressive effect of catalpol on glucosamine-induced NOX4 over-expression was weakened by knockdown of AMPK with siRNA. Taken together, these findings suggested that catalpol ameliorated hepatic insulin resistance in type 2 diabetes through acting on AMPK/NOX4/PI3K/AKT pathway.