Variation in gene expression of presenilins-associated rhomboid-like protein and mitochondrial function in skeletal musc
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ORIGINAL ARTICLE
Variation in gene expression of presenilins-associated rhomboid-like protein and mitochondrial function in skeletal muscle of insulin-resistant rats Huiqin Tang • Jie Liu • Li Niu • Wenbo He Yancheng Xu
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Received: 18 June 2009 / Accepted: 21 September 2009 / Published online: 27 October 2009 Ó Humana Press 2009
Abstract Multiple factors promote insulin resistance. In this study, we evaluated the mRNA levels of presenilinsassociated rhomboid-like protein (PARL) and mitochondrial content and enzyme activity from skeletal muscle isolated from insulin-resistant rats. Rats fed a high-fat diet for 35 days developed moderate insulin resistance, which was determined by an increase in plasma glucose and insulin concentrations following an oral glucose tolerance test. The PARL mRNA level was lower in the insulinresistant rats than in control animals, and is associated with low mitochondrial content and reduced mitochondrial enzyme activity in the skeletal muscle from the insulinresistant rats. The results suggest that high-fat-diet-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle, and may be the result of the decreased expression of the PARL gene, which encodes the protein with functional significance in mitochondria.
Huiqin Tang and Jie Liu contributed equally to this work. H. Tang J. Liu L. Niu Y. Xu (&) Department of Endocrinology, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, People’s Republic China e-mail: [email protected] H. Tang e-mail: [email protected] J. Liu e-mail: [email protected] L. Niu e-mail: [email protected] W. He Medical School of Wuhan University, 430071 Wuhan, Hubei, People’s Republic China e-mail: [email protected]
Keywords Gastrocnemius muscle High-fat diet Insulin resistance Mitochondrial function Presenilins-associated rhomboid-like protein
Introduction Insulin resistance (IR), which is related to obesity, decreases the insulin response and glucose metabolism in a variety of tissues. This can lead to diabetes, abnormal lipid metabolism, and related complications such as cardiovascular disease, hypertension, and inflammation of peripheral tissues. Therefore, preventing insulin resistance is important for reducing the risk of developing these diseases. The role of skeletal muscle mitochondrial dysfunction in the development of insulin resistance has been a topic of intense interest recently. There are a number of studies that support the hypothesis that an overall reduction in the capacity of mitochondria to mediate oxidation phosphorylation occurs in the elderly, and this may also mediate insulin resistance [1]. The presenilins-associated rhomboid-like protein (PARL) gene is a newly discovered gene, which belongs to the Rhomboid superfamily of membrane proteins. This protein superfamily is highly conserved among eukaryotes, archaea, and bacteria. Recent studies have demonstrated that, in addition to regulating mitochondrial dynamics, PARL mediates mammalian-specific, developmentally regulated mitochondria-tonuc
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