Globular Adiponectin Enhances Muscle Insulin Action via Microvascular Recruitment and Increased Insulin Delivery
Rationale: Adiponectin enhances insulin action and induces nitric oxide-dependent vasodilatation. Insulin delivery to muscle microcirculation and trans-endothelial transport are two discrete steps that limit insulin's action. We have shown that expansion of muscle microvascular surface area increases muscle insulin delivery and action.
Objective: To examine whether adiponectin modulates muscle microvascular recruitment thus insulin delivery and action in vivo.
Methods and Results: Overnight fasted, adult male rats were studied. We determined the effects of adiponectin on muscle microvascular recruitment using contrast-enhanced ultrasound (CEU), on insulin-mediated microvascular recruitment and whole body glucose disposal using CEU and insulin clamp, and on muscle insulin clearance and uptake with 125I-insulin. Globular adiponectin (gAd) potently increased muscle microvascular blood volume without altering microvascular blood flow velocity, leading to a significantly increased microvascular blood flow. This was paralleled by a ~30-40% increase in muscle insulin uptake and clearance, and ~30% increase in insulin-stimulated whole body glucose disposal. Inhibition of endothelial nitric oxide synthase (eNOS) abolished gAd-mediated muscle microvascular recruitment and insulin uptake. In cultured endothelial cells, gAd dose-dependently increased eNOS phosphorylation but had no effect on endothelial cell internalization of insulin.
Conclusions: gAd increases muscle insulin uptake by recruiting muscle microvasculature, which contributes to its insulin-sensitizing action.
- Received October 25, 2012.
- Revision received March 1, 2013.
- Accepted March 4, 2013.