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

被引:29
作者
Araújo, RC
Mori, MA
Merino, VF
Bascands, JL
Schanstra, JP
Zollner, RL
Villela, CA
Nakaie, CR
Paiva, ACM
Pesquero, JL
Bader, M
Pesquero, JB [1 ]
机构
[1] Univ Fed Sao Paulo, Dept Biophys, BR-04023062 Sao Paulo, Brazil
[2] Univ Mogi das Cruzes, BR-08780911 Sao Paulo, Brazil
[3] CHU Rangueil, INSERM, U388, Inst Louis Bugnard, F-31432 Toulouse, France
[4] Univ Estadual Campinas, Dept Internal Med, BR-13081970 Campinas, SP, Brazil
[5] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany
基金
巴西圣保罗研究基金会;
关键词
diabetes; glucose; insulin; kinin B1 receptor; kinins; pancreas;
D O I
10.1515/BC.2006.057
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:431 / 436
页数:6
相关论文
共 35 条
[21]   International union of pharmacology.: XLV.: Classification of the kinin receptor family:: from molecular mechanisms to pathophysiological consequences [J].
Leeb-Lundberg, LMF ;
Marceau, F ;
Müller-Esterl, W ;
Pettibone, DJ ;
Zuraw, BL .
PHARMACOLOGICAL REVIEWS, 2005, 57 (01) :27-77
[22]   Effects of radiation therapy on vascular responsiveness [J].
Levesque, L ;
Lam, MH ;
Allaire, P ;
Mondat, M ;
Houle, S ;
Beaudoin, G ;
Donath, D ;
Leclerc, G .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2001, 37 (04) :381-393
[23]  
LUKINIUS A, 1995, AM J PATHOL, V146, P429
[24]   Bradykinin receptor ligands: Therapeutic perspectives [J].
Marceau, F ;
Regoli, D .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (10) :845-852
[25]   Increased insulin sensitivity and hypoinsulinemia in APS knockout mice [J].
Minami, A ;
Iseki, M ;
Kishi, K ;
Wang, M ;
Ogura, M ;
Furukawa, N ;
Hayashi, S ;
Yamada, M ;
Obata, T ;
Takeshita, Y ;
Nakaya, Y ;
Bando, Y ;
Izumi, K ;
Moodie, SA ;
Kajiura, F ;
Matsumoto, M ;
Takatsu, K ;
Takaki, S ;
Ebina, Y .
DIABETES, 2003, 52 (11) :2657-2665
[26]   Decreased urinary kallikrein with hyperglycemia in patients with short-term insulin-dependent diabetes mellitus [J].
Pelikanova, T ;
Pinsker, P ;
Smrckova, I ;
Stribrna, L ;
Dryakova, M .
JOURNAL OF DIABETES AND ITS COMPLICATIONS, 1998, 12 (05) :264-272
[27]   Molecular cloning and functional characterization of a mouse bradykinin B1 receptor gene [J].
Pesquero, JB ;
Pesquero, JL ;
Oliveira, SM ;
Roscher, AA ;
Metzger, R ;
Ganten, D ;
Bader, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 220 (01) :219-225
[28]   Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors [J].
Pesquero, JB ;
Araujo, RC ;
Heppenstall, PA ;
Stucky, CL ;
Silva, JA ;
Walther, T ;
Oliveira, SM ;
Pesquero, JL ;
Paiva, ACM ;
Calixto, JB ;
Lewin, GR ;
Bader, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (14) :8140-8145
[29]  
RODRIGUEZ A, 2005, 16 SCI M INT AM SOC
[30]   Inhibitory effect of a novel bradykinin B1 receptor antagonist, R-954, on enhanced vascular permeability in type 1 diabetic mice [J].
Simard, B ;
Gabra, BH ;
Sirois, P .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 2002, 80 (12) :1203-1207