April 21, 2006Circulation Research

Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca 2+ Currents via Increased PI3Kα/PKB Signaling

Q: What is the clinical evidence from this study?

Study design: Other. Intervention: PTEN deletion and IGF-1 application vs. Littermate controls. Primary outcome: Basal I(Ca,L) densities (p=<0.01).

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Key result

Inactivation of PTEN or treatment with IGF-1 enhanced cardiac L-type Ca2+ currents via a PI3Kalpha-dependent increase in PKB activation (P<0.01 for PTEN-/- vs controls).

Population

Myocytes isolated from mice overexpressing a dominant-negative p110alpha mutant in the heart, lacking the…

Comparison

Inactivation of PTEN or application of… vs Littermate controls or untreated myocytes.

Design

Preclinical

Authors

HSHui SunJohns Hopkins University BKBenoît‐Gilles KerfantMaastricht University DZDongling ZhaoInstitute of Molecular Biotechnology

Discussion

Member takes

Implication

p110α loss reduces I(Ca,L) and contractility in mice; leaves open its therapeutic relevance in human HF.

Structured PICO

Population

Myocytes isolated from mice overexpressing a dominant-negative p110alpha mutant (DN-p110alpha) in the heart, lacking the PI3Kgamma gene (PI3Kgamma(-/-)) or with muscle-specific ablation of PTEN (PTEN(-/-)), and combinations thereof, along with littermate controls.

Intervention

Inactivation of PTEN or application of insulin-like growth factor-1 (IGF-1), with or without pharmacological inhibition of PI3Ks or protein kinase B (PKB).

Comparator

Littermate controls or untreated myocytes.

Outcome

L-type Ca2+ channel current (I(Ca,L)) density and voltage dependence of current activation.surrogate

Main Result

p-value: p=<0.01

IGF-1 treatment or inactivation of PTEN enhances cardiac L-type Ca2+ currents via a PI3Kalpha-dependent increase in PKB activation.

Cite This Study

Sun et al. (2006) studied this question. PTEN deletion and IGF-1 application vs. Littermate controls was evaluated on Basal I(Ca,L) densities (p=<0.01). Inactivation of PTEN or treatment with IGF-1 enhanced cardiac L-type Ca2+ currents via a PI3Kalpha-dependent increase in PKB activation (P<0.01 for PTEN-/- vs controls).

synapsesocial.com/papers/6a62e15a50e2b8a4ef6a77dd https://doi.org/10.1161/01.res.0000223321.34482.8c

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Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca 2+ Currents via Increased PI3Kα/PKB Signaling

Discussion

Member takes

Implication

Structured PICO

Main Result

Cite This Study

Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca 2+ Currents via Increased PI3Kα/PKB Signaling

Discussion

Member takes

Implication

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider