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Journal of Gastrointestinal & Digestive System | ISSN: 2161-069X | Volume: 8

October 29-30, 2018 | San Francisco, USA

International Conference on

Gastrointestinal Cancer and Therapeutics

World Congress on

Digestive & Metabolic Diseases

Annual Congress on

Cancer Science and Targeted Therapies

p66Shc regulates vascular dysfunction and renal damage in diabetic nephropathy

atients with poorly-controlled diabetes mellitus sustain damage to the macro and microvasculature that is responsible for

much of the morbidity and mortality associated with the disease. In the kidney, dysregulation of glomerular blood flow

has been implicated as one factor in the pathogenesis of diabetic glomerulosclerosis. Increased expression of adaptor protein

p66Shc has been associated with progression of diabetic nephropathy. Afferent arteriolar dilation and glomerular hyperfiltration

in diabetes are due to increased KATP channel availability and activity. Hyperglycemia was induced in Dahl SS (SS) rats in a

model of type 1 diabetes via injection of streptozotocin (STZ). Albuminuria and glomerular injury were evaluated in SS and

genetically modified SS lacking either p66Shc (p66ShcKO) or expressing p66Shc mutant (p66Shc-S36A). Afferent arteriolar

diameter responses during STZ-induced hyperfiltration were determined using the juxtamedullary nephron technique to

assess the role of p66Shc in KATP activity. Albuminuria and glomerular injury were mitigated in p66ShcKO and p66Shc-

S36A rats with STZ-induced diabetes. SS rats with STZ-induced diabetes had a significant increase in the afferent arteriolar

diameter, whereas p66ShcKO and p66Shc-S36A rats did not. STZ SS rats, but not STZ p66ShcKO or p66Shc-S36A rats had

an increased vasodilator response to KATP channel activator pinacidil. Likewise, KATP inhibitor glibenclamide resulted in a

greater decrease in afferent arteriolar diameter in STZ SS rats compared to STZ-treated SS p66ShcKO and p66Shc-S36A rats.

Taken together, these results indicate that deletion of the adaptor protein p66Shc decreases afferent arteriolar KATP channel

activity and decreases renal damage in diabetic SS rats.

Biography

Andrey Sorokin graduated from the St Petersburg State University and received his PhD from the Institute of Cytology Academy of Sciences of Russia in 1981. He

is a Head of the Laboratory at the Medical College of Wisconsin, where he is holding the position of Full Professor with secondary appointments at Department of

Physiology and Department of Microbiology & Immunology. He has published more than 100 papers in reputed journals and serving as an editorial board member

of a number of journals including Frontiers in Renal and Epithelial Physiology.

sorokin@mcw.edu

Andrey Sorokin

Medical College of Wisconsin, USA

Andrey Sorokin, J Gastrointest Dig Syst 2018, Volume 8

DOI: 10.4172/2161-069X-C8-084