Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function.

Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Research Abstract Details 

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Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Abstract Text:

Palle G Laustsen,Steven J Russell,Lei Cui,Amelia Entingh-Pearsall,Martin Holzenberger,Ronglih Liao,C Ronald Kahn,

Cardiovascular disease is the leading cause of death in people with type 2 diabetes and is linked to insulin resistance even in the absence of diabetes. Here we show that mice with combined deficiency of the insulin receptor and insulin-like growth factor 1 (IGF-1) receptor in cardiac and skeletal muscle develop early-onset dilated cardiomyopathy and die from heart failure within the first month of life despite having a normal glucose homeostasis. Mice lacking the insulin receptor show impaired cardiac performance at 6 months, and mice lacking the insulin receptor plus one Igf1r allele have slightly increased mortality. By contrast, mice lacking the IGF-1 receptor or the IGF-1 receptor plus one Ir allele appear normal. Morphological characterization and oligonucleotide array analysis of gene expression demonstrate that prior to development of these physiological defects, mice with combined deficiency of both insulin and IGF-1 receptors have a coordinated down-regulation of genes encoding components of the electron transport chain and mitochondrial fatty acid beta-oxidation pathways and altered expression of contractile proteins. Thus, while neither the insulin receptor nor IGF-1 receptor in muscle is critical for glucose homeostasis during the first month of life, signaling from these receptors, particularly the insulin receptor, is required for normal cardiac metabolism and function.

Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Publishing Authors By Initials

PG Laustsen,SJ Russell,L Cui,A Entingh-Pearsall,M Holzenberger,R Liao,CR Kahn,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biology

VOLUME: 27

Page Numbers: 1649-64

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 0270-7306

DAY: 22

MONTH: 12

YEAR: 2006

Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Information

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LANGUAGE: eng

NlmUniqueID: 8109087

Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: physiology

Chemical & Substance for Abstract: Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Information

Substance Name: Receptor, IGF Type 1

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function.

AFFILIATION: Joslin Diabetes Center, Boston, MA 02215, USA. c.ronald.kahn@joslin.harvard.edu

Country: United States

AGENCY: United States NIDDK

GRANT: DK 31036

ACRONYM: DK

MEDLINETA: Mol Cell Biol

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