N K Verma1, C S Dey. 1. Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
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-beta, IRS-1, c-Jun N-terminal kinase, p38 and glycogen synthase kinase beta, 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.
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-beta, IRS-1, c-Jun N-terminal kinase, p38 and glycogen synthase kinase beta, 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.
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