Insulin Treatment Attenuates Renal ADAM17 and ACE2 Shedding in Akita Diabetic Mice.

Insulin Treatment Attenuates Renal ADAM17 and ACE2 Shedding in Akita Diabetic Mice. Am J Physiol Renal Physiol. 2014 Jan 22; Authors: Salem ES, Grobe N, Elased KM Abstract Angiotensin converting enzyme 2 (ACE2) is located in several tissues and is highly expressed in renal proximal tubules, where it degrades the vasoconstrictor angiotensin II (Ang-II) to Ang-(1-7). Accumulating evidence supports protective roles of ACE2 in several disease states, including diabetic nephropathy. A disintegrin and metalloprotease (ADAM) 17, is involved in the shedding of several transmembrane proteins, including ACE2. Our previous studies showed increased renal ACE2, ADAM17 expression, and urinary ACE2 in type 2 diabetic mice. The aim of the present study was to determine the effect of insulin on ACE2 shedding and ADAM17 in type 1 diabetic Akita mice. Results demonstrate increased renal ACE2 and ADAM17 expression, increased urinary ACE2 fragments (≈ 70 kDa) and albumin excretion in Akita diabetic mice. Immunostaining revealed co-localization of ACE2 with ADAM17 in renal tubules. Renal proximal tubular cells treated with ADAM17 inhibitor showed reduced ACE2 shedding into the media confirming ADAM17-mediated shedding of ACE2. Treatment of Akita mice with insulin implants for 20 weeks normalized hyperglycemia, and decreased urinary ACE2 and albumin excretion. Insulin also normalized renal ACE2, ADAM17, but had no effect on tissue inhibitors of metalloproteinase 3...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research