Role of the kinin B-1 receptor in insulin homeostasis and pancreatic islet function
Data
2006-04-01
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Resumo
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 B-2) 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 B-1 receptor (B-1(-/-) mice) have lower fasting plasma glucose concentrations but exhibit higher glycemia after feeding when compared to wild-type mice. B-1(-/-) 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 B-1(-/-) mice. in line with this phenotype, pancreatic vascular permeability was shown to be reduced in B-1 receptor-ablated mice. the B-1 agonist desArg(9)bradykinin injected intravenously can induce the release of insulin into serum, and this effect was not observed in the B-1(-/-) mice or in isolated islets. Our data demonstrate the importance of the kinin B-1 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.
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Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 387, n. 4, p. 431-436, 2006.