Increased ACE 2 and decreased ACE protein in renal tubules from diabetic mice: a renoprotective combination?

Hypertension. 2004 May;43(5):1120-5. doi: 10.1161/01.HYP.0000126192.27644.76. Epub 2004 Apr 12.


Unlike the ubiquitous angiotensin-converting enzyme (ACE), the ACE-related carboxypeptidase 2 (ACE 2) is predominantly expressed in the heart, kidney, and testis. ACE 2 degrades angiotensin (Ang) II to Ang (1-7) and Ang I to Ang (1-9). We investigated the expression of ACE and ACE 2 in a rodent model of type 2 diabetes. ACE and ACE 2 were measured in kidney and heart from 8-week-old no diabetic control (db/m) mice and diabetic (db/db) mice, which at this young age have obesity and hyperglycemia without nephropathy. In renal cortical tissue, ACE mRNA was reduced (db/db 0.31+/-0.06 versus db/m 0.99+/-0.05; P<0.005), whereas ACE 2 mRNA was not (db/db 0.94+/-0.05 versus db/m 1.03+/-0.11, NS). ACE protein was markedly reduced in kidney cortex of db/db mice (db/db 0.24+/-0.13 versus db/m 1.02+/-0.12; P<0.005), and this was associated with a corresponding decrease in renal ACE activity (db/db 12.7+/-3.7 versus db/m 61.6+/-4.4 mIU/mg protein; P<0.001). ACE 2 protein, by contrast, was increased in kidneys from diabetic mice (db/db 1.39+/-0.14 versus db/m 0.53+/-0.04; P<0.005). An increase in ACE 2 protein and a decrease in ACE protein, respectively, were also seen by immunostaining of renal cortical tubules from the db/db mice. In heart tissue, there were no significant differences between db/db and db/m mice in either ACE mRNA and protein or ACE 2 mRNA and protein. We conclude that in young db/db mice, ACE 2 protein in renal cortical tubules is increased, whereas ACE protein is decreased. We propose that the pattern of low ACE protein coupled with increased ACE 2 protein expression may be renoprotective in early stages of diabetes.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin I / metabolism*
  • Angiotensin II / metabolism*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Blood Glucose / analysis
  • Carboxypeptidases / biosynthesis*
  • Carboxypeptidases / genetics
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Nephropathies / prevention & control*
  • Enzyme Induction
  • Kidney Tubules / enzymology*
  • Lipids / blood
  • Lung / enzymology
  • Membrane Proteins / metabolism
  • Mice
  • Myocardium / enzymology
  • Organ Size
  • Organ Specificity
  • Peptidyl-Dipeptidase A / biosynthesis*
  • Peptidyl-Dipeptidase A / genetics
  • RNA, Messenger / biosynthesis
  • Renin-Angiotensin System / physiology


  • Blood Glucose
  • Lipids
  • Membrane Proteins
  • RNA, Messenger
  • Angiotensin II
  • Angiotensin I
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2