| 논문명 | [BT] Diacylglycerol-mediated insulin resistance | ||
| 저자명 | Derek M Erion & Gerald I Shulman | ||
| 잡지명 | NAT MED | 발행연도 | 2010 |
| 권호사항 | 16 | 수록면 | 400-402 |
| ABSTRACT |
Understanding the molecular mechanisms of insulin resistance remains a major medical challenge of the twenty-first century. Over the last half-century, many hypotheses have been proposed to explain insulin resistance, and, most recently, inflammation associated with alterations in adipocytokines has become the prevailing hypothesis. Here we discuss diacylglycerol-mediated insulin resistance as an alternative and unifying hypothesis to explain the most common forms of insulin resistance associated with obesity and type 2 diabetes mellitus, as well as lipodystrophy and aging. |
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| 내용 |
당뇨병 인구는 전 세계적으로 3억명에 육박하고 미국의 경우 인구의 7%가 당뇨병으로 고생하고 있다. 베타세포의 기능이상이 고혈당으로의 진행의 주요 이유임이 알려져 있고 인슐린 저항성이 베타세포의 기능이상을 앞당기는 것으로 알려져 있다. 그래서 인슐린저항성의 병인을 이해하는 것은 중요하다.
Lipid-induced liver insulin resistance Figure Molecular mechanisms of cellular insulin resistance in muscle and liver. Increased intracellular diacyglycerols lead to activation of PKC-θ and PKC-ε in skeletal muscle and liver, respectively, which, in turn, decreases insulin-stimulated IRS-1/IRS-2 tyrosine phosphorylation, PI3K activation and downstream insulin signaling. (a) In the muscle, this results in decreased muscle glycogen synthesis, owing to reduced insulin-stimulated GLUT4 translocation to the plasma membrane. (b) In the liver, this results in decreased hepatic glycogen synthesis, owing to decreased activation of glycogen synthase, and increased hepatic gluconeogenesis. The use of transgenic and knockout mice, as well as antisense oligonucleotides to knock down specific proteins, has allowed the validation of the diacylglycerol-mediated insulin hypothesis of insulin resistance through the manipulation of key proteins in the pathway. KO, knockout; GLUT4, glucose transporter type 4; TAG, triacylglycerol; LPL, lipoproteinlipase; Tg, transgenic; FATP-1, fatty acid transport protein-1; DGAT, diacylglycerol O-acyltransferase; UCP3, uncoupling protein-3; GS, glycogen synthase; LCAD, long-chain acyl-CoA dehydrogenase; mtGPAT, mitochondrial glycerol-3-phosphate acyltransferase; ASO, antisense oligonucleotide.
한국화학연구원 대사증후군치료제연구센터 안진희 박사 제공
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| 원문보기 | http://www.nature.com/nm/journal/v16/n4/full/nm0410-400.html | ||
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