T2D is associated with devastating micro- and macro-vascular complications. Notably, exercise stimulates peripheral blood flow, improves cardiac function, reduces blood pressure and increases endurance capacity in man, and AMPK activation in endothelial and smooth muscle cells increases vasodilation and microvascular perfusion in muscle, and reduces blood pressure. Moreover, exercise can activate AMPK in heart, increase cardiac glucose uptake, reduce glycogen levels, and improve left ventricular (LV) stroke volume. Thus, AMPK activation may mitigate microvascular complications and reduce macrovascular events in T2D.

O304, microvascular perfusion and cardiac function

O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. O304 also activated AMPK in heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved LV stroke volume in mice, but did not increase heart weight in mice or rats. Thus, the major metabolic and vascular effects in animals translated to T2D patients.