Endothelial Mechanisms Contributing to Type 2 Diabetes Development

In both humans and rodent models over 80% of total body glucose disposal occurs in the skeletal muscle, and an impaired capacity of insulin to promote muscle glucose disposal is a major component of type 2 diabetes pathogenesis. We discovered that diminished insulin transport across the endothelial cell monolayer in muscle plays a key role in obesity-related peripheral insulin resistance. We are presently investigating how muscle insulin delivery is normally promoted by processes in endothelium, and how impairments in the process explain how a number of key risk factors for type 2 diabetes lead to the condition. We are doing so by characterizing insulin-induced capillary recruitment in skeletal muscle using contrast-enhanced ultrasound (CEUS), and in studies of transendothelial insulin transport.

Capillary blood flow visualized in mouse skeletal muscle using contrast-enhanced ultrasound.