title: Constitutive activation of the renin-angiotensin system reduces visceral fat and improves glucose tolerance in mice.
abstract: BACKGROUND
  The renin-angiotensin system (RAS), and particularly angiotensin II, is involved in the control of energy balance, glucose homeostasis and kidney functions. The integrated impact of the RAS on glucose homeostasis is still a matter of debate.
  
  
  METHODS
  We used a model of constitutive RAS activation in double transgenic mice (dTGM) carrying both human angiotensinogen and human renin genes. We evaluated energy balance, measured renal functions, performed glucose and insulin tolerance tests, and used ramipril to inhibit the angiotensin-converting enzyme.
  
  
  RESULTS
  dTGM had a lower physical activity and an increased food intake without change in body weight. Renal impairment was characterized by low-grade albuminuria. High urinary output secondary to polydipsia was associated with proximal tubule dysfunction. Compared to controls, dTGM had a lower hyperglycemia induced by an intraperitoneal glucose administration. This decrease was not due to changes in insulin sensitivity and/or secretion. dTGM had an increased creatinine production and a lower epididymal fat mass. Acute inhibition of angiotensin-converting enzyme with ramipril did not suppress this improved glucose tolerance profile.
  
  
  CONCLUSIONS
  Chronic RAS activation is not sufficient to cause insulin resistance in mice. Moreover, adaptation to constitutive RAS activation in mice results in a better glucose tolerance.
authors.affiliation: INSERM, U 1081, Institute for Research on Cancer and Aging of Nice (IRCAN), "Aging and Diabetes" team, France Nephrology Department, University Hospital, Nice, France favre@unice.fr.
authors.forename: Guillaume A
authors.initials: GA
authors.lastname: Favre
authors.affiliation: INSERM, U 1081, Institute for Research on Cancer and Aging of Nice (IRCAN), "Aging and Diabetes" team, France University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lebrun
authors.affiliation: INSERM, U 1081, Institute for Research on Cancer and Aging of Nice (IRCAN), "Aging and Diabetes" team, France University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lopez
authors.affiliation: Clinical and Experimental Pathology Department, University Hospital, Nice, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Butori
authors.affiliation: University of Nice-Sophia Antipolis, Nice, France Clinical and Experimental Pathology Department, University Hospital, Nice, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.affiliation: INSERM, U 1081, Institute for Research on Cancer and Aging of Nice (IRCAN), "Aging and Diabetes" team, France Nephrology Department, University Hospital, Nice, France.
authors.forename: Vincent Lm
authors.initials: VL
authors.lastname: Esnault
authors.affiliation: INSERM, U 1081, Institute for Research on Cancer and Aging of Nice (IRCAN), "Aging and Diabetes" team, France University of Nice-Sophia Antipolis, Nice, France Clinical Chemistry Laboratory, University Hospital, Nice, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Van Obberghen
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D004326:Drinking / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010641:Phenotype; D017257:Ramipril / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D007328:Insulin; D000804:Angiotensin II; D003404:Creatinine; D017257:Ramipril
keywords: Renin-angiotensin system; metabolism; renal function