期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 59
卷 59, 期 -, 页码 65-87出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010716-104727
关键词
type 2 diabetes; insulin resistance; ectopic lipids; liver-targeted mitochondrial uncoupling
资金
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [K99 CA215315, R00 CA215315] Funding Source: Medline
- NIDDK NIH HHS [F32 DK114954, P30 DK045735, R01 DK113984, R01 DK040936] Funding Source: Medline
Type 2 diabetes (T2D) is characterized by persistent hyperglycemia despite hyperinsulinemia, affects more than 400 million people worldwide, and is a major cause of morbidity and mortality. Insulin resistance, of which ectopic lipid accumulation in the liver [nonalcoholic fatty liver disease (NAFLD)] and skeletal muscle is the root cause, plays a major role in the development of T2D. Although lifestyle interventions and weight loss are highly effective at reversing NAFLD and T2D, weight loss is difficult to sustain, and newer approaches aimed at treating the root cause of T2D are urgently needed. In this review, we highlight emerging pharmacological strategies aimed at improving insulin sensitivity and T2D by altering hepatic energy balance or inhibiting key enzymes involved in hepatic lipid synthesis. We also summarize recent research suggesting that liver-targeted mitochondrial uncoupling may be an attractive therapeutic approach to treat NAFLD, nonalcoholic steatohepatitis, and T2D.
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