Troglitazone effects on gene expression in human skeletal muscle of type II diabetes involve up-regulation of peroxisome proliferator-activated receptor-γ

Kyong Soo Park, Theodore P. Ciaraldi, Kristin Lindgren, Leslie Abrams-Carter, Sunder Mudaliar, Svetlana E. Nikoulina, Sherrie R. Tufari, Jacques H. Veerkamp, Antonio Vidal-Puig, Robert R. Henry

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104 Scopus citations

Abstract

Troglitazone, besides improving insulin action in insulin-resistant subjects, is also a specific ligand for the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ). To determine whether troglitazone might enhance insulin action by stimulation of PPARγ gene expression in muscle, total PPARγ messenger RNA (mRNA), and protein were determined in skeletal muscle cultures from nondiabetic control and type II diabetic subjects before and after treatment of cultures with troglitazone (4 days ± troglitazone; 11.5 μM). Troglitazone treatment increased PPARγ mRNA levels up to 3-fold in muscle cultures from type II diabetics (277 ± 63 to 630 ± 100 x 103 copies/μg total RNA, P = 0.003) and in nondiabetic control subjects (200 ± 42 to 490 ± 81, P = 0.003). PPARγ protein levels in both diabetic (4.7 ± 1.6 to 13.6 ± 3.0 AU/10 μg protein, P < 0.02) and nondiabetic cells (7.4 ± 1.0 to 12.7 ± 1.8, P < 0.05) were also upregulated by troglitazone treatment. Increased PPARγ was associated with stimulation of human adipocyte lipid binding protein (ALBP) and muscle fatty acid binding protein (mFABP) mRNA, without change in the mRNA for glycerol-3-phosphate dehydrogenase, PPARδ, myogenin, uncoupling protein-2, or sarcomeric α- actin protein. In summary, we showed that troglitazone markedly induces PPARγ, ALBP, and mFABP mRNA abundance in muscle cultures from both nondiabetic and type II diabetic subjects. Increased expression of PPARγ protein and other genes involved in glucose and lipid metabolism in skeletal muscle may account, in part, for the insulin sensitizing effects of troglitazone in type II diabetes.

Original languageEnglish
Pages (from-to)2830-2835
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number8
DOIs
StatePublished - 10 Nov 1998

Cite this

Park, K. S., Ciaraldi, T. P., Lindgren, K., Abrams-Carter, L., Mudaliar, S., Nikoulina, S. E., Tufari, S. R., Veerkamp, J. H., Vidal-Puig, A., & Henry, R. R. (1998). Troglitazone effects on gene expression in human skeletal muscle of type II diabetes involve up-regulation of peroxisome proliferator-activated receptor-γ. Journal of Clinical Endocrinology and Metabolism, 83(8), 2830-2835. https://doi.org/10.1210/jc.83.8.2830