Skip to main content
Top
Published in: Diabetologia 7/2006

01-07-2006 | Short Communication

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

Authors: N. K. Verma, C. S. Dey

Published in: Diabetologia | Issue 7/2006

Login to get access

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.
Literature
1.
go back to reference Verma NK, Dey CS (2004) Possible mechanism of miltefosine mediated death of Leishmania donovani. Antimicrob Agents Chemother 48:3010–3016PubMedCrossRef Verma NK, Dey CS (2004) Possible mechanism of miltefosine mediated death of Leishmania donovani. Antimicrob Agents Chemother 48:3010–3016PubMedCrossRef
2.
go back to reference Terwogt JMM, Mandjes IAM, Sindermann H, Beijnen JH, ten Bokkel Huinink WW (1999) Phase II trial of topically applied miltefosine solution in patients with skin-metastasized breast cancer Br J Cancer 79:1158–1161PubMedCrossRef Terwogt JMM, Mandjes IAM, Sindermann H, Beijnen JH, ten Bokkel Huinink WW (1999) Phase II trial of topically applied miltefosine solution in patients with skin-metastasized breast cancer Br J Cancer 79:1158–1161PubMedCrossRef
3.
go back to reference Thakur BB (2003) Breakthrough in the management of visceral leishmaniasis. J Assoc Physicians India 51:649–651PubMed Thakur BB (2003) Breakthrough in the management of visceral leishmaniasis. J Assoc Physicians India 51:649–651PubMed
5.
go back to reference Ruiter GA, Zerp SF, Bartelink H, Blitterswijk WJV, Verheij M (2003) Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB/PKB survival pathway. Anti-Cancer Drugs 14:167–173PubMedCrossRef Ruiter GA, Zerp SF, Bartelink H, Blitterswijk WJV, Verheij M (2003) Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB/PKB survival pathway. Anti-Cancer Drugs 14:167–173PubMedCrossRef
7.
go back to reference Khurana A, Dey CS (2002) Involvement of ELK-1 in L6L9 skeletal muscle cell differentiation. FEBS Lett 527:119–124PubMedCrossRef Khurana A, Dey CS (2002) Involvement of ELK-1 in L6L9 skeletal muscle cell differentiation. FEBS Lett 527:119–124PubMedCrossRef
8.
go back to reference Kumar N, Dey CS (2003) Metformin enhances insulin signaling in insulin-dependent and -independent pathways in insulin resistant muscle cells. Br J Pharmacol 137:329–336CrossRef Kumar N, Dey CS (2003) Metformin enhances insulin signaling in insulin-dependent and -independent pathways in insulin resistant muscle cells. Br J Pharmacol 137:329–336CrossRef
9.
go back to reference Cusi K, Maezono K, Osman A et al (2000) Insulin resistance differentially affects the PI3-kinase and MAP kinase-mediated signaling in human muscle. J Clin Invest 105:311–320PubMedCrossRef Cusi K, Maezono K, Osman A et al (2000) Insulin resistance differentially affects the PI3-kinase and MAP kinase-mediated signaling in human muscle. J Clin Invest 105:311–320PubMedCrossRef
10.
go back to reference Manning AM, Davis R (2003) Targeting JNK for therapeutic benefit: from junk to gold? Nat Rev Drug Discov 2:554–565PubMedCrossRef Manning AM, Davis R (2003) Targeting JNK for therapeutic benefit: from junk to gold? Nat Rev Drug Discov 2:554–565PubMedCrossRef
Metadata
Title
The anti-leishmanial drug miltefosine causes insulin resistance in skeletal muscle cells in vitro
Authors
N. K. Verma
C. S. Dey
Publication date
01-07-2006
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2006
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0260-1

Other articles of this Issue 7/2006

Diabetologia 7/2006 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.