Effects of triglyceride on ER stress and insulin resistance.
This study was conducted to examine the mechanism by which triglyceride induces insulin resistance and ER stress in HepG2 cells. Using in vitro study models, we show that triglyceride causes insulin resistance through serine phosphorylation of insulin receptor substrate-1 (IRS-1). In addition, triglyceride induces the expression of endogenous endoplasmic reticulum (ER) stress markers, including GRP 78, IRE-1alpha, XBP-1, p-eIF2alpha, CHOP, and p-JNK. ER stress, in turn, leads to the suppression of insulin receptor signaling through tyrosine dephosphorylation of IRS-1. The results of this study show that triglyceride is a central feature of peripheral insulin resistance, and also suggest that triglyceride-induced ER stress influences insulin resistance. These experiments may be used in the development of an in vitro acute obesity model.
Kim
Do-Sung
DS
Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea.
Jeong
Seul-Ki
SK
Kim
Hyung-Ryong
HR
Kim
Dal-Sik
DS
Chae
Soo-Wan
SW
Chae
Han-Jung
HJ
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D014280:Triglycerides / Q000008:administration & dosage*
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D014280:Triglycerides