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(Circulation Research. 2003;92:707.)
© 2003 American Heart Association, Inc.

Editorials

A Novel Action of Insulin on Cardiac Membrane

Masayasu Hiraoka

From the Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

Correspondence to Masayasu Hiraoka, MD, PhD, Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. E-mail hiraoka.card@mri.tmd.ac.jp

Key Words: insulin • voltage-dependent nonselective cation channel • signaling pathway • diacylglycerol

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Insulin is an essential hormone for the control of blood glucose level and glucose metabolism. Additionally, insulin mediates a wide spectrum of biological responses including lipid metabolism, protein synthesis, activation of transcription of specific genes, modulation of cellular growth and differentiation, and functional regulation of ion channels and transporters in various types of cells. The action of insulin is mediated through the insulin receptor, a transmembrane glycoprotein with intrinsic protein tyrosine kinase activity. The insulin receptor is an 2/ß2 tetramer with the -subunit located on the extracellular face of the plasma membrane having the insulin binding site. The intracellular portion of the ß-subunit contains the insulin-regulated tyrosine protein kinase. Insulin action is exerted through its binding to the -subunit of the insulin receptor, resulting in regulation of the tyrosine protein kinase located in the ß-subunit of the insulin receptor. This leads to the autophosphorylation of the receptor and other substrates including insulin receptor substrate-1 (IRS-1) and other related proteins. Diverse and complex intracellular signaling pathways downstream to the receptor activation are involved in different responses depending on the target proteins, and it is believed that intrinsic tyrosine kinase is critical for the signal transduction of insulin action.R1-128043 ^1,2

Insulin receptors are also present in cardiac membranes. Because tissue sensitivity to insulin is dictated by receptor abundance, it is relevant to note that the number of functional insulin receptors in the heart is comparable to that in other insulin-sensitive cell types (10 000 to 100 000 per cell).³ In the heart, insulin . . . [Full Text of this Article]

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