Endothelial β1 Integrins are Necessary for Microvascular Function and Glucose Uptake.
Nathan C Winn1, Deborah A Roby1, P Mason McClatchey1
1Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA.
Biorxiv : the Preprint Server for Biology
|September 4, 2024
Summary
Endothelial cell integrin beta1 (itgβ1) is crucial for muscle microvascular function. Its loss impairs blood flow and insulin-stimulated glucose uptake, leading to delivery-mediated insulin resistance.
Area of Science:
- Physiology
- Molecular Biology
- Cardiovascular Science
Background:
- Microvascular insulin delivery to myocytes is a rate-limiting step for muscle glucose uptake.
- Integrins, transmembrane adhesion receptors, regulate microvasculature integrity.
- Endothelial cell (EC) integrin β1 (itgβ1) is vital for capillary network formation and microvascular responses.
Purpose of the Study:
- To investigate the role of skeletal muscle EC itgβ1 in microcirculatory function and glucose uptake.
- To determine if loss of EC itgβ1 causes 'delivery'-mediated insulin resistance.
Main Methods:
- Developed an inducible itgβ1 knockdown mouse model (itgβ1fl/flSCLcre).
- Quantified microcirculatory hemodynamics using intravital microscopy.
- Assessed insulin-stimulated glucose uptake via hyperinsulinemic-euglycemia clamp.
Main Results:
- itgβ1 knockdown mice exhibited deficits in capillary flow rate, heterogeneity, and density.
- Insulin-stimulated glucose uptake was impaired despite adequate insulin transcapillary transport.
- Reduced glucose uptake was attributed to perfusion-limited glucose delivery.
Conclusions:
- Skeletal muscle EC itgβ1 is essential for maintaining microcirculatory function.
- EC itgβ1 is necessary to meet the metabolic demands of insulin stimulation.
- Loss of EC itgβ1 leads to impaired glucose delivery and insulin resistance.
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