Renal effects of GLP-1

The GLP-1 receptor is expressed in many extra-pancretic tissues including the renal vascular smooth muscle cells. Treatment of rats and mice using GLP-1 increases blood pressure but also increases renal blood flow (RBF) and glomerular filtration rate (GFR). This indicates a direct vasodilating effect of GLP-1 in the kidney primarily in the pre-glomerular arterioles. Furthermore, GLP-1 reduces the ability of the renal afferent arterioles to autoregulate in response to acute pressure changes.

GLP-1 in renal autoregulation
We have found a reduced ability of afferent arterioles to autoregulate in response to acute pressure changes. We have used knock-out mice lacking expression of the GLP-1 receptor to verify that the effect is directly linked to vascular effects of GLP-1. We investigate this further using whole animals to assess the effect of GLP-1 on renal autoregulation during acute pressure changes.

GLP-1 receptors in human kidneys
We have shown expression of GLP-1 receptors in renal vascular smooth muscle cells in kidneys from rats and mice. We are further exploring this using human renal tissue from healthy, diabetic and hypertensive patients to examine the location and possible changes in expression during diseases.

GLP-1 in renal vascular responses
GLP-1 induces renal vasodilation. Whether this vasodilation depends on e.g. closure of Ca2+ channels or opening of K+ channels is unknown. In isolated renal vessels we are examining changes in intracellular Ca2+ and the effect of different ion channels inhibitors and activators to elucidate this.