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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 and João B. Pesquero
Published/Copyright: April 11, 2006
Biological Chemistry
From the journal Volume 387 Issue 4

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 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.

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References

Araújo, R.C., Kettritz, R., Fichtner, I., Paiva, A.C.M., Pesquero, J.B., and Bader, M. (2001). Altered neutrophil homeostasis in kinin B1 receptor-deficient mice. Biol. Chem.382, 91–95.10.1515/BC.2001.014Search in Google Scholar

Bhoola, K.D., Figueroa, C.D., and Worthy, K. (1992). Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol. Rev.44, 1–80.Search in Google Scholar

Chai, K.X., Ni, A., Wang, D., Ward, D.C., Chao, J., and Chao, L. (1996). Genomic DNA sequence, expression, and chromosomal localization of the human B1 bradykinin receptor gene BDKRB1. Genomics31, 51–57.10.1006/geno.1996.0008Search in Google Scholar

Chen, D., Mauvais-Jarvis, F., Bluher, M., Fisher, S.J., Jozsi, A., Goodyear, L.J., Ueki, K., and Kahn, C.R. (2004). p50α/p55α phosphoinositide 3-kinase knockout mice exhibit enhanced insulin sensitivity. Mol. Cell. Biol.24, 320–329.10.1128/MCB.24.1.320-329.2004Search in Google Scholar

Christopher, J. and Jaffa, A.A. (2002). Diabetes modulates the expression of glomerular kinin receptors. Int. Immunopharmacol.2, 1771–1779.10.1016/S1567-5769(02)00188-1Search in Google Scholar

Christopher, J., Velarde, V., and Jaffa, A.A. (2001a). Induction of B1-kinin receptors in vascular smooth muscle cells: cellular mechanisms of MAP kinase activation. Hypertension38, 602–605.10.1161/01.HYP.38.3.602Search in Google Scholar PubMed

Christopher, J., Velarde, V., Zhang, D., Mayfield, D., Mayfield, R.K., and Jaffa, A.A. (2001b). Regulation of B2-kinin receptors by glucose in vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol.280, H1537–1546.10.1152/ajpheart.2001.280.4.H1537Search in Google Scholar PubMed

Cloutier, F. and Couture, R. (2000). Pharmacological characterization of the cardiovascular responses elicited by kinin B1 and B2 receptor agonists in the spinal cord of streptozotocin-diabetic rats. Br. J. Pharmacol.130, 375–385.10.1038/sj.bjp.0703319Search in Google Scholar PubMed PubMed Central

Damas, J., Bourdon, V., and Lefebvre, P.J. (1999). Insulin sensitivity, clearance and release in kininogen-deficient rats. Exp. Physiol.84, 549–557.10.1111/j.1469-445X.1999.01812.xSearch in Google Scholar PubMed

Duka, I., Shenouda, S., Johns, C., Kintsurashvili, E., Gavras, I., and Gavras, H. (2001). Role of the B2 receptor of bradykinin in insulin sensitivity. Hypertension38, 1355–1360.10.1161/hy1201.096574Search in Google Scholar PubMed

Emanueli, C., Grady, E.F., Madeddu, P., Figini, M., Bunnett, N.W., Parisi, D., Regoli, D., and Geppetti, P. (1998). Acute ACE inhibition causes plasma extravasation in mice that is mediated by bradykinin and substance P. Hypertension31, 1299–1304.10.1161/01.HYP.31.6.1299Search in Google Scholar

Gabra, B.H. and Sirois, P. (2003). Beneficial effect of chronic treatment with the selective bradykinin B1 receptor antagonists, R-715 and R-954, in attenuating streptozotocin-diabetic thermal hyperalgesia in mice. Peptides8, 1131–1139.10.1016/j.peptides.2003.06.003Search in Google Scholar PubMed

Gotoh, M., Maki, T., Kiyoizumim, T., Satomi, S., and Monaco, A.P. (1985). An improved method for isolation of mouse pancreatic islets. Transplantation40, 437–438.10.1097/00007890-198510000-00018Search in Google Scholar PubMed

Henriksen, E.J. and Jacob, S. (2003). Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition. J. Cell. Physiol.196, 171–179.10.1002/jcp.10294Search in Google Scholar PubMed

Henriksen, E.J., Jacob, S., Kinnick, T.R., Youngblood, E.B., Schmit, M.B., and Dietze, G.J. (1999). ACE inhibition and glucose transport in insulin resistant muscle: roles of bradykinin and nitric oxide. Am. J. Physiol.277, R332–R336.Search in Google Scholar

Isami, S., Kishikawa, H., Araki, E., Uehara, M., Kaneko, K., Shirotani, T., Todaka, M., Ura, S., Motoyoshi, S., Matsumoto, K., et al. (1996). Bradykinin enhances GLUT4 translocation through the increase of insulin receptor tyrosine kinase in primary adipocytes: evidence that bradykinin stimulates the insulin signalling pathway. Diabetologia39, 412–420.10.1007/BF00400672Search in Google Scholar PubMed

Kishi, K., Muromoto, N., Nakaya, Y., Miyata, I., Hagi, A., Hayashi, H., and Ebina, Y. (1998). Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway. Diabetes47, 550–558.10.2337/diabetes.47.4.550Search in Google Scholar PubMed

Konstantinova, I. and Lammert, E. (2004). Microvascular development: learning from pancreatic islets. Bioessays26, 1069–1075.10.1002/bies.20105Search in Google Scholar PubMed

Kuebler, J.F., Schremmer-Danninger, E., Bhoola, K.D., Roscher, A.A., Messmer, K., and Hoffmann, T.F. (2003). Kinin-B1 receptors in ischaemia-induced pancreatitis: functional importance and cellular localisation. Biol. Chem.384, 1311–1319.10.1515/BC.2003.147Search in Google Scholar PubMed

Lawson, S.R., Gabra, B.H., Guerin, B., Neugebauer, W., Nantel, F., Battistini, B., and Sirois, P. (2005). Enhanced dermal and retinal vascular permeability in streptozotocin-induced type 1 diabetes in Wistar rats: blockade with a selective bradykinin B1 receptor antagonist. Regul. Pept.124, 221–224.10.1016/j.regpep.2004.09.002Search in Google Scholar PubMed

Leeb-Lundberg, L.M., Marceau, F., Muller-Esterl, W., Pettibone, D.J., and Zuraw, B.L. (2005). International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol. Rev.57, 27–77.Search in Google Scholar

Levesque, L., Lam, M.H., Allaire, P., Mondat, M., Houle, S., Beaudoin, G., Donath, D., and Leclerc, G. (2001). Effects of radiation therapy on vascular responsiveness. J. Cardiovasc. Pharmacol.37, 381–393.10.1097/00005344-200104000-00005Search in Google Scholar PubMed

Lukinius, A., Jansson, L., and Korsgren, O. (1995). Ultrastructural evidence for blood microvessels devoid of an endothelial cell lining in transplanted pancreatic islets. Am. J. Pathol.146, 429–435.Search in Google Scholar

Marceau, F. and Regoli, D. (2004). Bradykinin receptor ligands: therapeutic perspectives. Nat. Rev. Drug Discov.3, 845–852.10.1038/nrd1522Search in Google Scholar PubMed

Minami, A., Iseki, M., Kishi, K., Wang, M., Ogura, M., Furukawa, N., Hayashi, S., Yamada, M., Obata, T., Takeshita, Y., et al. (2003). Increased insulin sensitivity and hypoinsulinemia in APS knockout mice. Diabetes52, 2657–2665.10.2337/diabetes.52.11.2657Search in Google Scholar

Pelikanova, T., Pinsker, P., Smrckova, I., Stribrna, L., and Dryakova, M. (1998). Decreased urinary kallikrein with hyperglycemia in patients with short-term insulin-dependent diabetes mellitus. J. Diabetes Complications12, 264–272.10.1016/S1056-8727(98)00002-6Search in Google Scholar

Pesquero, J.B., Pesquero, J.L., Oliveira, S.M., Roscher, A., Metzger, R., Ganten, D., and Bader, M. (1996). Molecular cloning and functional characterization of a mouse bradykinin B1 receptor gene. Biochem. Biophys. Res. Commun.220, 219–225.10.1006/bbrc.1996.0384Search in Google Scholar

Pesquero, J.B., Araújo, R.C., Heppenstall, P.A., Stucky, C.L, Silva, J.A. Jr., Walther, T., Oliveira, S.M., Pesquero, J.L., Paiva, A.C., Calixto, J.B., et al. (2000). Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors. Proc. Natl. Acad. Sci. USA97, 8140–8145.10.1073/pnas.120035997Search in Google Scholar

Rodríguez, A., Pereira K, Boric MP, Velarde V. (2005). High glucose or hyperglycemia increases B1-kinin receptor expression and signaling in endothelial cells. In: XVIth Scientific Meeting of the Inter American Society of Hypertension, Cancun, Mexico.Search in Google Scholar

Simard, B., Gabra, B.H., and Sirois, P. (2002). Inhibitory effect of a novel bradykinin B1 receptor antagonist, R-954, on enhanced vascular permeability in type 1 diabetic mice. Can. J. Physiol. Pharmacol.80, 1203–1207.10.1139/y02-153Search in Google Scholar

Tschope, C., Walther, T., Yu, M., Reinecke, A., Koch, M., Seligmann, C., Heringer, S.B., Pesquero, J.B., Bader, M., Schultheiss, H., and Unger, T. (1999a). Myocardial expression of rat bradykinin receptors and two tissue kallikrein genes in experimental diabetes. Immunopharmacology15, 35–42.10.1016/S0162-3109(99)00109-5Search in Google Scholar

Tschope, C., Reinecke, A., Seidl, U., Yu, M., Gavriluk, V., Riester, U., Gohlke, P., Graf, K., Bader, M., Hilgenfeldt, U., et al. (1999b). Functional, biochemical, and molecular investigations of renal kallikrein-kinin system in diabetic rats. Am. J. Physiol.277, H2333–2340.10.1152/ajpheart.1999.277.6.H2333Search in Google Scholar

Yang, C. and Hsu, W.H. (1995). Stimulatory effect of bradykinin on insulin release from the perfused rat pancreas. Am. J. Physiol.268, E1027–E1030.10.1152/ajpendo.1995.268.5.E1027Search in Google Scholar

Yang, C. and Hsu, W.H. (1997). Glucose-dependency of bradykinin-induced insulin secretion from the perfused rat pancreas. Regul. Pept.71, 23–28.10.1016/S0167-0115(97)01011-2Search in Google Scholar

Zuccollo, A., Navarro, M., Frontera, M., Cueva, F., Carattino, M., and Catanzaro, O.L. (1999). The involvement of kallikreinkinin system in diabetes type I (insulitis). Immunopharmacology45, 69–74.10.1016/S0162-3109(99)00149-6Search in Google Scholar

Published Online: 2006-04-11
Published in Print: 2006-04-01

©2006 by Walter de Gruyter Berlin New York

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