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(Circulation Research. 2005;96:139.)
© 2005 American Heart Association, Inc.

Editorials

Another Role for the Celebrity

Akt and Insulin Resistance

Rong Tian

From the NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Rong Tian, MD, PhD, 221 Longwood Ave, Room 252, Boston, MA 02115. E-mail rtian@rics.bwh.harvard.edu

See related article, pages 180–188

Key Words: insulin signaling • Akt • phosphorylation • ß-adrenergic stimulation

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

Insulin is the most potent anabolic hormone and is essential for tissue development, growth, and maintenance of whole-body glucose homeostasis. Failure of the target cells to respond to insulin stimulation, ie, insulin resistance, is commonly observed under acute stress conditions and in individuals with obesity, metabolic syndrome, or diabetes. Insulin resistance has been considered a major risk factor for the development and progression of cardiovascular disease.^1,2 Although a well-documented phenomenon, the molecular mechanisms leading to insulin resistance remain elusive, attributable, in part, to the complexity of the insulin signaling pathway.

Circulating insulin binds to and activates its cell surface receptor to elicit its biological actions (Figure). The insulin receptor is a widely expressed transmembrane tyrosine kinase consisting of two - and two ß-subunits.^3,4 The binding of insulin to the extracellular -subunit results in a rapid configurational change in the receptor leading to the autophosphorylation of specific tyrosine residues of the intracellular region of the ß-subunit.⁵ This process results in activation of the tyrosine kinase activity of the insulin receptor, which transmits the insulin signal by phosphorylating a number of substrate proteins.^5,6 The insulin-receptor signaling involves two major pathways: the mitogen activated protein kinase (MAPK) pathway, mainly responsible for mitogenesis and cell growth, and the phosphatidylinositol-3-kinase (PI3-K) pathways, mainly account for the metabolic responses (Figure; although depicted as linear pathways, these two systems also interact under certain conditions). A critical player in the PI3-K pathway is the Ser/Thr kinase Akt (PKB), which serves as a multifaceted intermediary . . . [Full Text of this Article]

Related Article:

Akt Mediates the Cross-Talk Between ß-Adrenergic and Insulin Receptors in Neonatal Cardiomyocytes

Carmine Morisco, Gerolama Condorelli, Valentina Trimarco, Alessandro Bellis, Chiara Marrone, Gianluigi Condorelli, Junichi Sadoshima, and Bruno Trimarco
Circ. Res. 2005 96: 180-188. [Abstract] [Full Text] [PDF]

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