Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
December 6, 2004
李伯賢
Abstract
Obesity has been proven to be associated with some metabolic syndrome such as type 2 diabetes, cardiovascular disease etc. But the molecular mechanism underlying this association is still unknown. Though several conditions that trigger ER stress are also be found in obesity. So they postulated that obesity may be a chronic stimulus for ER stress which plays a key role in triggering insulin resistance and type 2 diabetes. They used ob/ob and high fat diet (HFD) mice to model obesity and seen significant ER stress responses in obese mice by detecting of phosphorylated elF2α and PERK in liver cells. Then they treat cells with tunicamycin or thapsgargin to induce ER stress and found out that ER stress is associated with insulin signaling through hyperactivation of JNK, IRE-1α mediating and XBP-1 regulating. Finally, XBP+/- mouse with HFD has been found intense ER stress and insulin resistance against wild type ones. So they concluded that ER stress link between obesity and insulin resistance.
From Science. 2004 Oct 15;306(5695):457-61.
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