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


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
Miltefosine may contribute to the risk of type 2 diabetes and needs further clinical exploration.
Verma
N K
NK
Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
Dey
C S
CS
D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010767:Phosphorylcholine / Q000009:adverse effects / Q000031:analogs & derivatives*; D051381:Rats
D000981:Antiprotozoal Agents; D007328:Insulin; D010767:Phosphorylcholine; C039128:miltefosine; D051058:Oncogene Protein v-akt; D005947:Glucose