Impaired autonomic regulation of the sinoatrial node in diabetes mellitus

Abstract

Diabetes mellitus type 1 (T1D) and type 2 (T2D) are frequently associated with a number of cardiovascular complications. Cardiovascular autonomic neuropathy (CAN) is a severe cardiovascular complication in diabetes and results in a progressive decline of proper autonomic regulation of heart rate. CAN is associated with impaired parasympathetic and sympathetic responsiveness of the heart and was originally thought to be solely a consequence of nerve damage. In this study we used both in vivo and ex vivo techniques to investigate the effects of parasympathetic and sympathetic agonists on the activity of the sinoatrial node (SAN) in diabetic mice. Our measurements show responsiveness of the SAN to sympathetic and parasympathetic agonists is blunted in diabetic mice and that this impairment is reversed by insulin treatment. This work implicates intrinsic alterations in the SAN itself in diabetes. These experiments provide novel insight into the impaired autonomic regulation of the heart in diabetes.