Dissecting the role of insulin resistance in the metabolic syndrome

被引:59
作者
Haas, Joel T. [2 ]
Biddinger, Sudha B. [1 ,2 ,3 ]
机构
[1] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA
[3] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA
关键词
cholesterol gallstones; dyslipidemia; forkhead box O1; hepatic fatty acid metabolism; sterol-regulatory element-binding protein-1c; ELEMENT-BINDING PROTEIN-1C; FATTY-ACID SYNTHESIS; LIPID-METABOLISM; RECEPTOR SUBSTRATE-1; TRANSCRIPTION FACTOR; GENE-EXPRESSION; HEPATIC GLUCOSE; MICE; CHOLESTEROL; LIVER;
D O I
10.1097/MOL.0b013e32832b2024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Purpose of review Over 20 years ago, insulin resistance was postulated to play a central role in the pathogenesis of the metabolic syndrome. However, this has been difficult to prove, leading to a great deal of controversy within the field. Recent studies on mice and humans with genetic defects in insulin signaling have allowed us, for the first time, to dissect which features of the metabolic syndrome can be caused by insulin resistance. Recent findings Liver insulin receptor knockout mice show that hepatic insulin resistance can produce hyperglycemia, increased apolipoprotein B secretion and atherosclerosis, and increased biliary cholesterol secretion and cholesterol gallstones. Many of these changes may be due to disinhibition of the transcription factor, forkhead box O1. Yet, neither liver insulin receptor knockout mice nor humans with insulin receptor mutations develop the hypertriglyceridemia or hepatic steatosis associated with the metabolic syndrome. Summary These data point to a central role for insulin resistance in the pathogenesis of the metabolic syndrome, as hyperglycemia, atherosclerosis, and cholesterol gallstones can all be caused by insulin resistance. However, hypertriglyceridemia and hepatic steatosis are not due directly to insulin resistance and should be considered pathogenically distinct features of the metabolic syndrome.
引用
收藏
页码:206 / 210
页数:5
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