Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice.
Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice.
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作者：
2型糖尿病（T2D）已在全球范围内达到流行病水平。目前大多数治疗方法改善了高血糖症状，但对纠正根本原因无效。引起T2D的一个重要因素是肝脏和肌肉等器官的脂质异位积聚。线粒体解偶联，降低细胞能量效率和增加脂质氧化，代表了一个有吸引力的治疗策略。然而，挑战在于发现安全的实际使用的线粒体解偶联剂。氯硝柳胺是一种FDA批准的驱虫药，可以使寄生虫的线粒体分离。在这里，我们展示了氯胺酮乙醇胺盐（NEN）在高纳摩尔浓度下解偶联哺乳动物线粒体。口服NEN增加小鼠的能量消耗和脂质代谢。对高脂饮食引起的肝脂肪变性和胰岛素抵抗有有效的防治作用。此外，它还能改善血糖控制，延缓db/db小鼠的疾病进展。鉴于NEN的安全性，我们的研究为治疗T2D的新策略提供了潜在的实用药理学体现。
Type 2 diabetes (T2D) has reached an epidemic level globally. Most current treatments ameliorate the hyperglycemic symptom but are not effective in correcting the underlying cause. One important causal factor of T2D is ectopic accumulation of lipid in organs such as liver and muscle. Mitochondrial uncoupling, which reduces cellular energy efficiency and increases lipid oxidation, represents an appealing therapeutic strategy. The challenge, however, is to discover safe mitochondrial uncouplers for practical use. Niclosamide is an FDA approved anthelmintic drug that uncouples mitochondria of parasitic worms. Here we show that niclosamide ethanolamine salt (NEN) uncouples mammalian mitochondria at upper nanomolar concentrations. Oral NEN increases energy expenditure and lipid metabolism in mice. It is efficacious in preventing and treating high-fat diet (HFD) induced hepatic steatosis and insulin resistance. Moreover, it improves glycemic control and delays disease progression of the db/db mice. Given the well- documented safety profile of NEN, our study provides a potentially practical pharmacological embodiment of a new strategy for treating T2D.
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DOI：
10.1046/j.1467-789x.2001.00043.x
发表时间：
2001-11-01
期刊：
Obesity reviews : an official journal of the International Association for the Study of Obesity
影响因子：
--
作者：
Harper, J A;Dickinson, K;Brand, M D
通讯作者：
Brand, M D
影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.
影响因子：
7.7
作者：
HENRY, RR;WALLACE, P;OLEFSKY, JM
通讯作者：
OLEFSKY, JM
影响因子：
15.9
作者：
Choi, Cheol Soo;Fillmore, Jonathan J.;Shulman, Gerald I.
通讯作者：
Shulman, Gerald I.
影响因子：
15.9
作者：
Kopecky, J;Clarke, G;Kozak, LP
通讯作者：
Kozak, LP