-Member Login

Forgot your USERNAME OR PASSWORD?

Job Postings

Let's Stay Connected

Find us on the popular social networks

Facebook Twitter LinkedIn Flicker

Journal Highlights

JPET Highlight: Selective Activation of AMPK β1-Containing Isoforms Improves Kidney Function in a Rat Model of Diabetic Nephropathy

Posted on 4/14/2017 4:14:27 PM

JPET May Highlights Salatto et al
 

Diabetic nephropathy remains an area of high unmet medical need, with current therapies that slow down, but do not prevent, the progression of disease. A reduced phosphorylation state of adenosine monophosphate-activated protein kinase (AMPK) has been correlated with diminished kidney function in both humans and animal models of renal disease. Here, we describe the identification of novel, potent, small molecule activators of AMPK that selectively activate AMPK heterotrimers containing the β1 subunit. After confirming that human and rodent kidney predominately express AMPK β1, we explore the effects of pharmacological activation of AMPK in the ZSF1 rat model of diabetic nephropathy. Chronic administration of these direct activators elevates the phosphorylation of AMPK in the kidney, without impacting blood glucose levels, and reduces the progression of proteinuria to a greater degree than the current standard of care, angiotensin-converting enzyme inhibitor ramipril. Further analyses of urine biomarkers and kidney tissue gene expression reveal AMPK activation leads to the modulation of multiple pathways implicated in kidney injury, including cellular hypertrophy, fibrosis, and oxidative stress. These results support the need for further investigation into the potential beneficial effects of AMPK activation in kidney disease.

See the article by Salatto et al. at Journal of Pharmacology and Experimental Therapeutics May 2017, 361 (2) 303-311; DOI: https://doi.org/10.1124/jpet.116.237925 

Comments (0)


Leave a comment


Blog comments are moderated and will be posted once approved.

Name


Comment:


Enter the code shown below:

Recent Posts

Archive

.

Hot Links 

EB2017 

Join ASPET 

What is Pharmacology? Video 

PharmTalk Blog