Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function.
Kinins are potent vasoactive peptides generated in blood and tissues by the kallikrein serine proteases. Two distinct kinin receptors have been described, one constitutive (subtype B2) and one inducible (subtype B1), and many physiological functions have been attributed to these receptors, including glucose homeostasis and control of vascular permeability. In this study we show that mice lacking the kinin B1 receptor (B1-/- mice) have lower fasting plasma glucose concentrations but exhibit higher glycemia after feeding when compared to wild-type mice. B1-/- mice also present pancreas abnormalities, characterized by fewer pancreatic islets and lower insulin content, which leads to hypoinsulinemia and reduced insulin release after a glucose load. Nevertheless, an insulin tolerance test indicated higher sensitivity in B1-/- mice. In line with this phenotype, pancreatic vascular permeability was shown to be reduced in B1 receptor-ablated mice. The B1 agonist desArg9bradykinin injected intravenously can induce the release of insulin into serum, and this effect was not observed in the B1-/- mice or in isolated islets. Our data demonstrate the importance of the kinin B1 receptor in the control of pancreatic vascular homeostasis and insulin release, highlighting a new role for this receptor in the pathogenesis of diabetes and related diseases.
Araújo
Ronaldo C
RC
Universidade de Mogi das Cruzes, 08780-911 São Paulo, Brazil.
Mori
Marcelo A
MA
Merino
Vanessa F
VF
Bascands
Jean-Loup
JL
Schanstra
Joost P
JP
Zollner
Ricardo L
RL
Villela
Conceição A
CA
Nakaie
Clovis R
CR
Paiva
Antonio C M
AC
Pesquero
Jorge L
JL
Bader
Michael
M
Pesquero
João B
JB
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002199:Capillary Permeability; D006706:Homeostasis / Q000502:physiology; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007515:Islets of Langerhans / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000502:physiology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D043783:Receptor, Bradykinin B1; D014665:Vasodilator Agents; C024626:bradykinin, des-Arg(9)-; D001920:Bradykinin