title: Kinin B1 receptor in adipocytes regulates glucose tolerance and predisposition to obesity.
abstract: BACKGROUND
  Kinins participate in the pathophysiology of obesity and type 2 diabetes by mechanisms which are not fully understood. Kinin B(1) receptor knockout mice (B(1) (-/-)) are leaner and exhibit improved insulin sensitivity.
  
  
  RESULTS
  Here we show that kinin B(1) receptors in adipocytes play a role in controlling whole body insulin action and glucose homeostasis. Adipocytes isolated from mouse white adipose tissue (WAT) constitutively express kinin B(1) receptors. In these cells, treatment with the B(1) receptor agonist des-Arg(9)-bradykinin improved insulin signaling, GLUT4 translocation, and glucose uptake. Adipocytes from B(1) (-/-) mice showed reduced GLUT4 expression and impaired glucose uptake at both basal and insulin-stimulated states. To investigate the consequences of these phenomena to whole body metabolism, we generated mice where the expression of the kinin B(1) receptor was limited to cells of the adipose tissue (aP2-B(1)/B(1) (-/-)). Similarly to B(1) (-/-) mice, aP2-B(1)/B(1) (-/-) mice were leaner than wild type controls. However, exclusive expression of the kinin B(1) receptor in adipose tissue completely rescued the improved systemic insulin sensitivity phenotype of B(1) (-/-) mice. Adipose tissue gene expression analysis also revealed that genes involved in insulin signaling were significantly affected by the presence of the kinin B(1) receptor in adipose tissue. In agreement, GLUT4 expression and glucose uptake were increased in fat tissue of aP2-B(1)/B(1) (-/-) when compared to B(1) (-/-) mice. When subjected to high fat diet, aP2-B(1)/B(1) (-/-) mice gained more weight than B(1) (-/-) littermates, becoming as obese as the wild types.
  
  
  CONCLUSIONS
  Thus, kinin B(1) receptor participates in the modulation of insulin action in adipocytes, contributing to systemic insulin sensitivity and predisposition to obesity.
authors.affiliation: Department of Biophysics, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Mori
authors.forename: Vicência Micheline
authors.initials: VM
authors.lastname: Sales
authors.forename: Fabiana Louise
authors.initials: FL
authors.lastname: Motta
authors.forename: Raphael Gomes
authors.initials: RG
authors.lastname: Fonseca
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Dioze
authors.initials: D
authors.lastname: Guadagnini
authors.forename: Ines
authors.initials: I
authors.lastname: Schadock
authors.forename: Elton Dias
authors.initials: ED
authors.lastname: Silva
authors.forename: Hugo A M
authors.initials: HA
authors.lastname: Torres
authors.forename: Edson Lucas
authors.initials: EL
authors.lastname: dos Santos
authors.forename: Charlles Heldan
authors.initials: CH
authors.lastname: Castro
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
authors.forename: Sandra
authors.initials: S
authors.lastname: Andreotti
authors.forename: Amanda Baron
authors.initials: AB
authors.lastname: Campaña
authors.forename: Rogério A L
authors.initials: RA
authors.lastname: Sertié
authors.forename: Mario J A
authors.initials: MJ
authors.lastname: Saad
authors.forename: Fabio Bessa
authors.initials: FB
authors.lastname: Lima
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D007705:Kinins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D007705:Kinins; D043783:Receptor, Bradykinin B1; D005947:Glucose