Overactive cannabinoid 1 receptor in podocytes drives type 2 diabetic nephropathy
Abstract
Diabetic nephropathy is the leading cause of chronic kidney disease in the United States, and one of the most significant long-term complications of both type 1 and type 2 diabetes, which currently lack fully effective therapy. Hyperglycemia and activation of the renin-angiotensin system (RAS) are thought to be the two main drivers of this pathology. We have recently shown that selective blockade of peripheral cannabinoid receptor-1 (CB1R) delayed and attenuated the development of type 2 diabetes in a rat model. Here we show that the nephropathy-inducing effects of both hyperglycemia and activation of the RAS involve CB1R activation in glomerular podocytes, and that antagonism of peripheral CB1R could represent a novel, effective, and rational approach to both prevent and reverse diabetic nephropathy.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2014
- DOI:
- 10.1073/pnas.1419901111
- Bibcode:
- 2014PNAS..111E5420J