1. cardiovascular and renal systems
Figure 9 Beneficial effects of SGLT2 inhibition on glucose homeostasis and the
cardiovascular and renal systems
Figure 9 | Beneficial effects of SGLT2 inhibition on glucose homeostasis and the cardiovascular and renal systems. The primary effect of SGLT2 inhibitors is to promote the excretion of glucose and sodium (Na+) by the kidney. In the kidney, this increased excretion results in afferent arteriole vasoconstriction, reduced intraglomerular pressure and normalization of the glomerular filtration rate (GFR) and provides protection against the development of diabetic nephropathy. Decreased renal glucose reabsorption results in a widening of the difference in arteriovenous glucose concentration, which can activate the renal nerves and transmit a neurogenic signal to the liver (and to the kidney) to augment hepatic (and renal) glucose production. The increase in urinary glucose excretion (60–80 g per day) reduces blood glucose concentration, ameliorating glucotoxicity and markedly augmenting β-cell function and muscle insulin sensitivity by promoting GLUT4 translocation to the cell membrane. Inhibition of SGLT2 in the α cell increases glucagon secretion which, in concert with activation of the renal nerves and sympathetic nervous system (SNS), stimulates hepatic glucose production. The decreases in blood pressure (after load reduction), plasma volume (preload reduction), and arterial stiffness lead to a reduction in ventricular volume, wall stress, and myocardial oxygen consumption leading to a decrease in cardiovascular (CV) events and heart failure. HGP, hepatic glucose production.
DeFronzo, R. A. et al. (2016) Renal, metabolic and cardiovascular considerations of SGLT2 inhibition
Nat. Rev. Nephrol. doi: /nrneph