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Crosstalk between insulin and angiotensin II signalling systems
1Department of Medicine I and Unit for Metabolic Disease, IRCCSH San Raffaele, Milano, Italy.
Summary
Angiotensin II (AII) negatively impacts insulin signaling by promoting serine phosphorylation, which impairs PI3-kinase activity. This interaction between the renin-angiotensin system and insulin signaling may contribute to insulin resistance in hypertension.
Area of Science:
- Endocrinology
- Cardiovascular Physiology
- Molecular Biology
Background:
- Insulin resistance and hypertension frequently coexist.
- Inhibition of the renin-angiotensin system (RAS) improves both conditions.
- This suggests a potential interaction between RAS and insulin signaling pathways.
Purpose of the Study:
- To investigate the relationship between insulin and angiotensin II (AII) intracellular signaling.
- To elucidate the molecular mechanisms underlying this interaction in vivo and in vitro.
Main Methods:
- Utilized an intact rat heart model for in vivo studies.
- Employed rat aorta smooth muscle cells (RASMC) for in vitro experiments.
- Assessed tyrosine and serine phosphorylation of insulin signaling components, including insulin receptor substrates (IRS-1, IRS-2) and PI3-kinase.
Main Results:
- AII stimulates tyrosine phosphorylation of IRS-1 and IRS-2, promoting their binding to PI3-kinase.
- AII inhibits insulin-stimulated PI3-kinase activity in a dose-dependent manner via the AT1 receptor.
- In vitro, AII interferes with IRS-1 docking to PI3-kinase by stimulating serine phosphorylation of IRS-1 and p85 subunit.
Conclusions:
- AII negatively modulates insulin signaling by inducing serine phosphorylation in early signaling components.
- Overactive RAS may impair insulin signaling, contributing to insulin resistance in essential hypertension.