Abstract
Insulin-induced genes (Insigs) including Insig-1 and Insig-2, are proteins that mediate sterol regulation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). Insigs perform distinct tasks in the regulation of these effectors: they promote the endoplasmic reticulum (ER) retention of SCAP, but ubiquitin-mediated degradation of HMG-CoA reductase. Through these activities, Insig-1 and Insig-2 influence cholesterol metabolism, lipogenesis, and glucose homeostasis in diverse tissues such as adipose tissue and liver. In this article, we focus on the functions, expression and regulation, gene polymorphisms of Insigs, and their deficiency with diseases.
Copyright © 2010. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amino Acid Sequence
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Animals
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Cholesterol / metabolism
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Homeostasis / physiology
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Humans
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Insulin / genetics
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / physiology*
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Lipid Metabolism / drug effects*
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Lipid Metabolism / physiology
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Lipogenesis / physiology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Polymorphism, Genetic
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Sterol Regulatory Element Binding Proteins / physiology
Substances
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INSIG1 protein, human
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INSIG2 protein, human
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Insig1 protein, mouse
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Insulin
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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SREBP cleavage-activating protein
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Sterol Regulatory Element Binding Proteins
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Cholesterol