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September 20, 2022Molecular and Cellular BiologyOpen Access

Insulin and Insulin-Like Growth Factor 1 Signaling Preserves Sarcomere Integrity in the Adult Heart

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Why the study?

The physiological and redundant roles of insulin and IGF1 signaling in adult hearts were not fully elucidated.

Population

Mice with inducible cardiomyocyte-specific deletion of insulin and IGF1 receptors or IRS1 and IRS2

Design

Preclinical animal study

Follow-up

8 weeks post-gene deletion

Authors

CRChristian RiehleEWEric T. WeatherfordNMNicholas S. McCarty

Discussion

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Overview

Loss of cardiomyocyte insulin/IGF1 signaling causes lethal dilated cardiomyopathy in mice; leaves open its role in human heart failure.

Structured PICO

P
Population
Adult mice with inducible cardiomyocyte-specific deletion of insulin and IGF1 receptors (iCIR2KO) or IRS1 and IRS2 (iCIRS12KO)
I
Intervention
Inducible gene deletion via doxycycline administration; subset treated with daily intraperitoneal branched-chain amino acids (BCAA)
C
Comparator
Wildtype (WT) controls
O
Outcome
Development of dilated cardiomyopathy and mortality

Constitutive insulin and IGF1 signaling is essential for maintaining sarcomere integrity and preventing rapid onset of heart failure in the adult heart via an SRF-mediated transcriptional program.

Cite This Study

Riehle et al. (2022) studied this question.

synapsesocial.com/papers/6a720ed226770c2b8de151e3https://doi.org/10.1128/mcb.00163-22
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Co-Activation of Nuclear Factor-κB and Myocardin/Serum Response Factor Conveys the Hypertrophy Signal of High Insulin Levels in Cardiac Myoblasts2014 · 24 citations
  2. 2Insulin receptor substrates differentially exacerbate insulin-mediated left ventricular remodeling2020 · 26 citations
  3. 3Temporally Controlled Onset of Dilated Cardiomyopathy Through Disruption of the <i>SRF</i> Gene in Adult Heart2005 · 169 citations
  4. 4Thin Filament Protein Dynamics in Fully Differentiated Adult Cardiac Myocytes: Toward A Model of Sarcomere Maintenance1999 · 79 citations
  5. 5Molecular basis of cardiac performance. Plasticity of the myocardium generated through protein isoform switches.1989 · 310 citations