Abstract
Podocyte injury plays an important role in the development of diabetic nephropathy. Podocytes are insulin-responsive and can develop insulin resistance, but the mechanisms are unknown. To study the role of CD2-associated protein (CD2AP) in podocyte injury, we performed a yeast two-hybrid screening on a glomerular library, and found that CD2AP bound to SH2-domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2), a negative regulator of insulin signalling. SHIP2 interacts with CD2AP in glomeruli and is expressed in podocytes, where it translocates to plasma membrane after insulin stimulation. Overexpression of SHIP2 in cultured podocytes reduces Akt activation in response to insulin, and promotes apoptosis. SHIP2 is upregulated in glomeruli of insulin resistant obese Zucker rats. These results indicate that SHIP2 downregulates insulin signalling in podocytes. The upregulation of SHIP2 in Zucker rat glomeruli prior to the age of onset of proteinuria suggests a possible role for SHIP2 in the development of podocyte injury.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
