Effects of troglitazone on cellular differentiation, insulin signaling, and glucose metabolism in cultured human skeletal muscle cells

Kausch, C; Krützfeldt, J; Witke, A; Rettig, A; Bachmann, O; Rett, K; Matthaei, S; Machicao, F; Häring, H U; Stumvoll, M (2001). Effects of troglitazone on cellular differentiation, insulin signaling, and glucose metabolism in cultured human skeletal muscle cells. Biochemical and biophysical research communications, 280(3), pp. 664-74. Orlando, Fla.: Academic Press 10.1006/bbrc.2000.4216

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To determine the immediate effect of thiazolidinediones on human skeletal muscle, differentiated human myotubes were acutely (1 day) and myoblasts chronically (during the differentiation process) treated with troglitazone (TGZ). Chronic TGZ treatment resulted in loss of the typical multinucleated phenotype. The increase of muscle markers typically observed during differentiation was suppressed, while adipocyte markers increased markedly. Chronic TGZ treatment increased insulin-stimulated phosphatidylinositol (PI) 3-kinase activity and membranous protein kinase B/Akt (PKB/Akt) Ser-473 phosphorylation more than 4-fold. Phosphorylation of p42/44 mitogen-activated protein kinase (42/44 MAPK/ERK) was unaltered. Basal glucose uptake as well as both basal and insulin-stimulated glycogen synthesis increased approximately 1.6- and approximately 2.5-fold after chronic TGZ treatment, respectively. A 2-fold stimulation of PI 3-kinase but no other significant TGZ effect was found after acute TGZ treatment. In conclusion, chronic TGZ treatment inhibited myogenic differentiation of that human muscle while inducing adipocyte-specific gene expression. The effects of chronic TGZ treatment on basal glucose transport may in part be secondary to this transdifferentiation. The enhancing effect on PI 3-kinase and PKB/Akt involved in both differentiation and glycogen synthesis appears to be pivotal in the cellular action of TGZ.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Endocrinology, Diabetology and Clinical Nutrition

UniBE Contributor:

Krützfeldt, Jan

ISSN:

0006-291X

ISBN:

11162573

Publisher:

Academic Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:06

Last Modified:

04 May 2014 23:20

Publisher DOI:

10.1006/bbrc.2000.4216

PubMed ID:

11162573

Web of Science ID:

000166697300014

URI:

https://boris.unibe.ch/id/eprint/28599 (FactScience: 121991)

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