Schematic diagram showing the improvement of insulin sensitivity by gAd replenishment via
AMPK-mediated restoration of microvascular insulin response
Ad, adiponectin; AdipoR1/R2, adiponectin receptor 1/2; IR, insulin receptor. In the insulin sensitive state, adiponectin and insulin are able to stimulate endothelial NO production through the AdipoR1/2–APPL1–AMPK–eNOS and IR–Akt–eNOS pathways, respectively, leading to capillary recruitment and increased insulin delivery to muscle and thus increased muscle glucose uptake. In the insulin-resistant state, both adiponectin and insulin actions on endothelial cells are impaired, which results in reduced capillary response and decreased muscle insulin delivery and action (muscle glucose uptake). Replenishment of adiponectin could restore endothelial response to insulin.