Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function

Ronaldo C. Araújo, Marcelo A. Mori, Vanessa F. Merino, Jean Loup Bascands, Joost P. Schanstra, Ricardo L. Zollner, Conceição A. Villela, Clovis R. Nakaie, Antonio C.M. Paiva, Jorge L. Pesquero, Michael Bader, João B. Pesquero

Research output: Contribution to journalArticlepeer-review

Abstract

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 B 1), 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 (B 1-/- 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.

Original languageEnglish (US)
Pages (from-to)431-436
Number of pages6
JournalBiological Chemistry
Volume387
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • Diabetes
  • Glucose
  • Insulin
  • Kinin B1 receptor
  • Kinins
  • Pancreas

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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