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

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

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

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-I 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.

Original languageEnglish (US)
Pages (from-to)1649-1664
Number of pages16
JournalMolecular and Cellular Biology
Volume27
Issue number5
DOIs
StatePublished - Mar 2007
Externally publishedYes

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Somatomedin Receptors
Insulin Receptor
Insulin
Homeostasis
Alleles
Gene Components
Glucose
Contractile Proteins
IGF Type 1 Receptor
Dilated Cardiomyopathy
Electron Transport
Oligonucleotide Array Sequence Analysis
Type 2 Diabetes Mellitus
Insulin Resistance
Cause of Death
Myocardium
Skeletal Muscle
Cardiovascular Diseases
Fatty Acids
Down-Regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. / Laustsen, Palle G.; Russell, Stephen J; Cui, Lei; Entingh-Pearsall, Amelia; Holzenberger, Martin; Liao, Ronglih; Kahn, C. Ronald.

In: Molecular and Cellular Biology, Vol. 27, No. 5, 03.2007, p. 1649-1664.

Research output: Contribution to journalArticle

Laustsen, Palle G. ; Russell, Stephen J ; Cui, Lei ; Entingh-Pearsall, Amelia ; Holzenberger, Martin ; Liao, Ronglih ; Kahn, C. Ronald. / Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 5. pp. 1649-1664.
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