Urinary prorenin/renin and soluble prorenin receptor excretion in Type 1 and Type 2 diabetes

Abstract

BackgroundActivation of the intra‐renal, rather than systemic, renin angiotensin system (RAS) has been suggested to play a role in the development of diabetic kidney disease. In this study, we examined plasma and urinary prorenin/renin levels and urinary soluble prorenin receptor (sPRR) levels in mice with early Type 1 and Type 2 diabetes.MethodsMale Akita (Type 1 model bearing a mutated Ins2 gene) and db/db (Type 2 model bearing a mutated LepR gene) mice were studied from 10–18 weeks age and metabolic balance studies conducted at 4 week intervals on a normal salt diet.ResultsDiabetic mice were hyperglycemic (Akita: 479 ± 31, db/db: 314 ± 60, control: 152 ± 12 mg/dL), polyuric (Akita: 22.2 ± 3.9, db/db: 10.9 ± 2.3, controls 1.6 ± 0.1 ml/day) and polydipsic (Akita: 24.6 ± 3.4, db/db: 11.5 ± 2.4, controls: 4.2 ± 0.5 ml/day) at 10 weeks which continued until 18 weeks. Compared to controls, Akita mice had lower body weight (23.4 ± 0.6 vs controls: 29.2 ± 0.3 grams) while db/db mice had higher body weight (51.9 ± 0.3 g/day) at 10 weeks which continued until 18 weeks. Compared to controls, urinary angiotensinogen and total prorenin/renin levels were increased in Akita mice at 10 weeks and remained elevated at 14 and 18 weeks of age (Table 1); these increases were proportionally greater than changes in urinary albumin excretion. Urinary sPRR excretion was markedly increased in Akita mice at 14 and 18 weeks. In contrast, db/db mice had higher urinary albumin excretion, urinary angiotensinogen and urinary prorenin/renin excretion relative to controls at all 3 time points but undetectable urinary sPRR excretion until 18 weeks. Plasma renin concentration was similar between the controls and diabetic mice at all time points. There was mild glomerular hypertrophy at 18 weeks of age in db/db but not Akita mice.ConclusionThere is early activation of the intra‐renal but not systemic RAS in Type 1 and 2 diabetes. However, the pattern of intra‐renal RAS component activation appears to differ between Type 1 and 2 diabetes.Support or Funding InformationUniversity of Utah Internal Medicine Academic Excellence Seed GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.