Research press release


Nature Medicine

A potential new drug class for diabetes type 2 treatment


ニクロサミドは、寄生虫のミトコンドリアのATP(細胞のエネルギー源)合成能を低下させることによって、寄生虫の成長を阻害する。Victor Jinたちは、このATP合成阻害活性を2型糖尿病の治療に活用しようと、ニクロサミドの塩、ニクロサミドエタノールアミン(NEN)を遺伝性のマウスモデルと食餌性マウスモデルに投与した。するとNENが肝臓に選択的に蓄積し、肝臓でのミトコンドリアのATP合成能を低下させることが分かった。細胞のATPレベルが低下すると、シグナル分子が活性化され、肝細胞に貯蔵脂肪の燃焼量を増やすよう、情報を伝達する。


A derivative of the drug niclosamide, currently used to treat parasitic worm infections, is now found to relieve diabetic complications in mouse models of type 2 diabetes, reports a paper published this week in Nature Medicine.

Niclosamide works by reducing the ability of parasitic worm’s mitochondria to synthesize ATP (cellular energy), thus inhibiting worm growth. Victor Jin and colleagues exploited this activity of the drug, using niclosamide ethanolamine (NEN), a salt form of niclosamide, to treat both a genetic and a dietary model of type 2 diabetes in mice. They found that NEN predominately accumulates in the liver and reduces the ability of the mitochondria in this organ to efficiently synthesis ATP. The lower cellular levels of ATP results in the activation of a signalling molecule, which signals the liver cells to increase the burning of stored fat.

A hallmark of type 2 diabetes is insulin resistance, in which cells fail to respond to insulin resulting in increased levels of blood glucose. Jin and colleagues report that the reduction of fat in the liver cells enabled them to respond to insulin and reduce levels of blood glucose. The increased intracellular fat burning in the liver of the treated mice also reduced the incidence of fatty liver, another common complication of type 2 diabetes.

doi: 10.1038/nm.3699


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