title: Effect of insulin on ACE2 activity and kidney function in the non-obese diabetic mouse.
abstract: We studied the non-obese diabetic (NOD) mice model because it develops autoimmune diabetes that resembles human type 1 diabetes. In diabetic mice, urinary albumin excretion (UAE) was ten-fold increased at an "early stage" of diabetes, and twenty-fold increased at a "later stage" (21 and 40 days, respectively after diabetes diagnosis) as compared to non-obese resistant controls. In NOD Diabetic mice, glomerular enlargement, increased glomerular filtration rate (GFR) and increased blood pressure were observed in the early stage. In the late stage, NOD Diabetic mice developed mesangial expansion and reduced podocyte number. Circulating and urine ACE2 activity were markedly increased both, early and late in Diabetic mice. Insulin administration prevented albuminuria, markedly reduced GFR, blood pressure, and glomerular enlargement in the early stage; and prevented mesangial expansion and the reduced podocyte number in the late stage of diabetes. The increase in serum and urine ACE2 activity was normalized by insulin administration at the early and late stages of diabetes in Diabetic mice. We conclude that the Diabetic mice develops features of early kidney disease, including albuminuria and a marked increase in GFR. ACE2 activity is increased starting at an early stage in both serum and urine. Moreover, these alterations can be completely prevented by the chronic administration of insulin.
authors.affiliation: Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Riera
authors.affiliation: Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Márquez
authors.affiliation: Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Clotet
authors.affiliation: Department of Pathology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gimeno
authors.affiliation: Department of Pathology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Heleia
authors.initials: H
authors.lastname: Roca-Ho
authors.affiliation: Department of Pathology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.affiliation: Department of Pathology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Juanpere
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Batlle
authors.affiliation: Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.affiliation: Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Soler
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure; D003928:Diabetic Nephropathies / Q000097:blood / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2