期刊
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
卷 14, 期 4, 页码 367-373出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MCO.0b013e32834778d4
关键词
diabetes; insulin resistance; nonalcoholic fatty liver disease; transcription factors; unfolded protein response
资金
- [NIH ROI DK046546]
- [NIH ROI DK083572]
Purpose of review Balancing glucose homeostasis is crucial to maintain appropriate energy and metabolic state. Chronic hyperglycemia with insulin resistance and development of type II diabetes mellitus is a growing health and health-economic threat. The unfolded protein response (UPR) is a mechanism by which the endoplasmic reticulum copes with diverse physiological and pathophysiological stress stimuli. Unresolved and chronic endoplasmic reticulum stress are important features in the development of diabetes mellitus. Understanding how the UPR impacts glucose balance and what disrupts this balance is critical for development of future therapies. Recent findings In pancreatic beta-cells, evidence is growing that the single branches of the UPR work in concert to supply insulin in response to acute glucose availability. Chronic glucose stimulation disrupts these primarily adaptive changes into an overwhelming UPR, which leads to reduced insulin supply and beta-cell mass due to apoptosis. In hepatocytes, the UPR interacts with key transcription factors to physiologically regulate glucose and lipid homeostasis. Prolonged endoplasmic reticulum stress disrupts these feedback loops and results in ongoing gluconeogenesis and steatosis. Summary Unraveling the molecular networks underlying the adaptive and contra-adaptive roles of the UPR in glucose metabolism will identify novel therapeutic approaches in the battle against diabetes mellitus.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据