Verma N K, Dey C S
Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
Diabetologia. 2006 Jul;49(7):1656-60. doi: 10.1007/s00125-006-0260-1. Epub 2006 May 3.
AIMS/HYPOTHESIS: Miltefosine, the first oral anti-leishmanial drug, is reported to inhibit phosphatidylinositol 3-kinase (PI3K)/Akt activity in carcinoma cell lines. Inhibition of the PI3K/Akt pathway is known to result in insulin resistance. Therefore, we investigated whether miltefosine has any deleterious effect(s) on insulin sensitivity in L6E9 skeletal muscle cells.
L6E9 myotubes were treated with miltefosine and its effect was observed on insulin-signalling proteins such as Akt, PI3K, insulin receptor-beta, IRS-1, c-Jun N-terminal kinase, p38 and glycogen synthase kinase beta, as well as on glucose uptake.
Miltefosine caused skeletal muscle insulin resistance in vitro by interfering with the insulin-signalling pathway and inhibiting insulin-stimulated glucose uptake.
CONCLUSIONS/INTERPRETATION: Miltefosine may contribute to the risk of type 2 diabetes and needs further clinical exploration.
目的/假设：米替福新是第一种口服抗利什曼原虫药物，据报道它能抑制癌细胞系中的磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）活性。已知抑制PI3K/Akt途径会导致胰岛素抵抗。因此，我们研究了米替福新对L6E9骨骼肌细胞胰岛素敏感性是否有任何有害影响。
用米替福新处理L6E9肌管，并观察其对Akt、PI3K、胰岛素受体β、胰岛素受体底物-1（IRS-1）、c-Jun氨基末端激酶、p38和糖原合酶激酶β等胰岛素信号蛋白以及葡萄糖摄取的影响。
米替福新通过干扰胰岛素信号通路并抑制胰岛素刺激的葡萄糖摄取，在体外导致骨骼肌胰岛素抵抗。
结论/解读：米替福新可能会增加2型糖尿病风险，需要进一步的临床研究。
