RGD Reference Report - Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression. - Rat Genome Database

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Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression.

Authors: Belke, DD  Betuing, S  Tuttle, MJ  Graveleau, C  Young, ME  Pham, M  Zhang, D  Cooksey, RC  McClain, DA  Litwin, SE  Taegtmeyer, H  Severson, D  Kahn, CR  Abel, ED 
Citation: Belke DD, etal., J Clin Invest 2002 Mar;109(5):629-39.
RGD ID: 1302524
Pubmed: PMID:11877471   (View Abstract at PubMed)
PMCID: PMC150890   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI13946   (Journal Full-text)

To investigate the role of insulin signaling on postnatal cardiac development, physiology, and cardiac metabolism, we generated mice with a cardiomyocyte-selective insulin receptor knockout (CIRKO) using cre/loxP recombination. Hearts of CIRKO mice were reduced in size by 20-30% due to reduced cardiomyocyte size and had persistent expression of the fetal beta-myosin heavy chain isoform. In CIRKO hearts, glucose transporter 1 (GLUT1) expression was reduced by about 50%, but there was a twofold increase in GLUT4 expression as well as increased rates of cardiac glucose uptake in vivo and increased glycolysis in isolated working hearts. Fatty acid oxidation rates were diminished as a result of reduced expression of enzymes that catalyze mitochondrial beta-oxidation. Although basal rates of glucose oxidation were reduced, insulin unexpectedly stimulated glucose oxidation and glycogenolysis in CIRKO hearts. Cardiac performance in vivo and in isolated hearts was mildly impaired. Thus, insulin signaling plays an important developmental role in regulating postnatal cardiac size, myosin isoform expression, and the switching of cardiac substrate utilization from glucose to fatty acids. Insulin may also modulate cardiac myocyte metabolism through paracrine mechanisms by activating insulin receptors in other cell types within the heart.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cardiomyopathy  ISOInsr (Mus musculus)1302524; 1302524 RGD 
cardiomyopathy  IMP 1302524 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)

Genes (Mus musculus)
Insr  (insulin receptor)

Genes (Homo sapiens)
INSR  (insulin receptor)


Additional Information