Endothelial β1-integrins are necessary for microvascular function and glucose uptake

Area of Science:

• Physiology
• Molecular Biology
• Cardiovascular Research

Background:

• Microvascular insulin delivery to myocytes is a rate-limiting step for insulin-stimulated muscle glucose uptake.
• Integrins, transmembrane adhesion receptors, regulate capillary structural integrity. The integrin β1 (itgβ1) subunit is highly expressed in endothelial cells (ECs).

Purpose of the Study:

• To investigate the role of EC itgβ1 in microcirculatory function and glucose uptake, particularly in skeletal muscle.
• To determine if loss of EC itgβ1 causes "delivery"-mediated insulin resistance.

Main Methods:

• Developed an itgβ1 knockdown mouse model (itgβ1fl/flSCLcre) to study EC itgβ1 function.
• Quantified microcirculatory hemodynamics using intravital microscopy.
• Assessed insulin-stimulated glucose uptake using a hyperinsulinemic-euglycemia clamp.

Main Results:

• Mice with itgβ1 knockdown exhibited deficits in capillary flow rate, flow heterogeneity, and capillary density.
• Insulin-stimulated glucose uptake was impaired despite adequate insulin transcapillary efflux.
• Reduced glucose uptake was attributed to perfusion-limited glucose delivery.

Conclusions:

• Endothelial cell itgβ1 is essential for maintaining microcirculatory function.
• EC itgβ1 is necessary to meet the metabolic demands of insulin stimulation.
• Reduced EC itgβ1 expression leads to microcirculatory dysfunction and insulin resistance.