The anti-leishmanial drug miltefosine causes insulin resistance in skeletal muscle cells in vitro

Abstract

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. Materials and methods: L6E9 myotubes were treated with miltefosine and its effect was observed on insulin-signalling proteins such as Akt, PI3K, insulin receptor-β, IRS-1, c-Jun N-terminal kinase, p38 and glycogen synthase kinase β, as well as on glucose uptake. Results: 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. © Springer-Verlag 2006.