Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats
Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats Anna Abella 1 , Luc Marti 1 , Marta Camps 1 , Marc Claret 2 , J. Fernández-Alvarez 2 , Ramon Gomis 2 , Anna Gumà 1 , Nathalie Viguerie 3 , Christian Carpéné 3 , Manuel Palac...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2003-04, Vol.52 (4), p.1004-1013 |
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| creator | ABELLA, Anna MARTI, Luc TESTAR, Xavier ZORZANO, Antonio CAMPS, Marta CLARET, Marc FERNANDEZ-ALVAREZ, J GOMIS, Ramon GUMA, Anna VIGUERIE, Nathalie CARPENE, Christian PALACIN, Manuel |
| description | Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki
Rats
Anna Abella 1 ,
Luc Marti 1 ,
Marta Camps 1 ,
Marc Claret 2 ,
J. Fernández-Alvarez 2 ,
Ramon Gomis 2 ,
Anna Gumà 1 ,
Nathalie Viguerie 3 ,
Christian Carpéné 3 ,
Manuel Palacín 1 ,
Xavier Testar 1 and
Antonio Zorzano 1
1 Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, and Parc Científic de Barcelona,
Barcelona, Spain
2 Endocrinology and Diabetes Unit, IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain
3 Institut National de la Santé et de la Recherche Médicale (INSERM U 317), Toulouse, France
Abstract
In this study we have explored whether the bifunctional protein semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion
protein-1 (VAP-1) represents a novel target for type 2 diabetes. To this end, Goto-Kakizaki (GK) diabetic rats were treated
with the SSAO substrate benzylamine and with low ineffective doses of vanadate previously shown to have antidiabetic effects
in streptozotocin-induced diabetic rats. The administration of benzylamine in combination with vanadate in type 2 diabetic
rats acutely stimulated glucose tolerance, and the chronic treatment normalized hyperglycemia, stimulated glucose transport
in adipocytes, and reversed muscle insulin resistance. Acute in vivo administration of benzylamine and vanadate stimulated
skeletal muscle glucose transport, an effect that was also observed in incubated muscle preparations coincubated with adipose
tissue explants or with human recombinant SSAO. Acute administration of benzylamine/vanadate also ameliorated insulin secretion
in diabetic GK rats, and this effect was also observed in incubated pancreatic islets. In keeping with these observations,
we also demonstrate that pancreatic islets express SSAO/VAP-1. As far as mechanisms of action, we have found that benzylamine/vanadate
causes enhanced tyrosine phosphorylation of proteins and reduced protein tyrosine phosphatase activity in adipocytes. In addition,
incubation of human recombinant SSAO, benzylamine, and vanadate generates peroxovanadium compounds in vitro. Based on these
data, we propose that benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates
insulin secretion and also produces peroxovanadium in adipose tissue, activating glucose metabolism in adipocytes and in neighboring
muscle. This opens the possibility of |
| doi_str_mv | 10.2337/diabetes.52.4.1004 |
| format | Article |
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Rats
Anna Abella 1 ,
Luc Marti 1 ,
Marta Camps 1 ,
Marc Claret 2 ,
J. Fernández-Alvarez 2 ,
Ramon Gomis 2 ,
Anna Gumà 1 ,
Nathalie Viguerie 3 ,
Christian Carpéné 3 ,
Manuel Palacín 1 ,
Xavier Testar 1 and
Antonio Zorzano 1
1 Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, and Parc Científic de Barcelona,
Barcelona, Spain
2 Endocrinology and Diabetes Unit, IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain
3 Institut National de la Santé et de la Recherche Médicale (INSERM U 317), Toulouse, France
Abstract
In this study we have explored whether the bifunctional protein semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion
protein-1 (VAP-1) represents a novel target for type 2 diabetes. To this end, Goto-Kakizaki (GK) diabetic rats were treated
with the SSAO substrate benzylamine and with low ineffective doses of vanadate previously shown to have antidiabetic effects
in streptozotocin-induced diabetic rats. The administration of benzylamine in combination with vanadate in type 2 diabetic
rats acutely stimulated glucose tolerance, and the chronic treatment normalized hyperglycemia, stimulated glucose transport
in adipocytes, and reversed muscle insulin resistance. Acute in vivo administration of benzylamine and vanadate stimulated
skeletal muscle glucose transport, an effect that was also observed in incubated muscle preparations coincubated with adipose
tissue explants or with human recombinant SSAO. Acute administration of benzylamine/vanadate also ameliorated insulin secretion
in diabetic GK rats, and this effect was also observed in incubated pancreatic islets. In keeping with these observations,
we also demonstrate that pancreatic islets express SSAO/VAP-1. As far as mechanisms of action, we have found that benzylamine/vanadate
causes enhanced tyrosine phosphorylation of proteins and reduced protein tyrosine phosphatase activity in adipocytes. In addition,
incubation of human recombinant SSAO, benzylamine, and vanadate generates peroxovanadium compounds in vitro. Based on these
data, we propose that benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates
insulin secretion and also produces peroxovanadium in adipose tissue, activating glucose metabolism in adipocytes and in neighboring
muscle. This opens the possibility of using the SSAO/VAP-1 activity as a local generator of protein tyrosine phosphatase inhibitors
in antidiabetic therapy.
Footnotes
Address correspondence and reprint requests to Antonio Zorzano, Department de Bioquímica i Biologia Molecular, Facultat de
Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028, Barcelona, Spain. E-mail: azorzano{at}porthos.bio.ub.es
Received for publication 3 December 2002 and accepted in revised form 8 January 2003.
A.A. and L.M. equally contributed to the study.
IAPP, islet amyloid polypeptide; IRS, insulin receptor substrate; LAR, leukocyte antigen-related phosphatase; NMR, nuclear
magnetic resonance; PTP1B, protein tyrosine phosphatase-1B; SHP2, src-homology phosphatase-2; SSAO, semicarbazide-sensitive
amine oxidase; VAP-1, vascular adhesion protein-1.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/diabetes.52.4.1004</identifier><identifier>PMID: 12663473</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adipocytes ; Adipocytes - metabolism ; Amine Oxidase (Copper-Containing) - administration & dosage ; Amine Oxidase (Copper-Containing) - genetics ; Amine Oxidase (Copper-Containing) - metabolism ; Animals ; Antidiabetics ; Benzylamines - administration & dosage ; Biological and medical sciences ; Biological Transport - drug effects ; Blood Glucose - analysis ; Body fat ; Cell Adhesion Molecules - metabolism ; Diabetes ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - physiopathology ; Diabetes therapy ; Enzyme Inhibitors - metabolism ; Fundamental and applied biological sciences. Psychology ; Glucose ; Glucose - metabolism ; Hyperglycemia ; Insulin - metabolism ; Insulin - pharmacology ; Insulin Resistance ; Insulin Secretion ; Islets of Langerhans - physiopathology ; Kinases ; Male ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Musculoskeletal system ; Peroxides - metabolism ; Phosphatase ; Phosphorylation ; Phosphotyrosine - metabolism ; Physiological aspects ; Plasma ; Protein Tyrosine Phosphatases - antagonists & inhibitors ; Proteins ; Rats ; Rats, Wistar ; Recombinant Proteins - administration & dosage ; Signal transduction ; Type 2 diabetes ; Vanadates - administration & dosage</subject><ispartof>Diabetes (New York, N.Y.), 2003-04, Vol.52 (4), p.1004-1013</ispartof><rights>2003 INIST-CNRS</rights><rights>COPYRIGHT 2003 American Diabetes Association</rights><rights>Copyright American Diabetes Association Apr 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c647t-ebb3f760c0a743fe7cfb7c03c632d9a2b387f532e4395ccf975803c1cd75b3093</citedby><cites>FETCH-LOGICAL-c647t-ebb3f760c0a743fe7cfb7c03c632d9a2b387f532e4395ccf975803c1cd75b3093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14698978$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12663473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ABELLA, Anna</creatorcontrib><creatorcontrib>MARTI, Luc</creatorcontrib><creatorcontrib>TESTAR, Xavier</creatorcontrib><creatorcontrib>ZORZANO, Antonio</creatorcontrib><creatorcontrib>CAMPS, Marta</creatorcontrib><creatorcontrib>CLARET, Marc</creatorcontrib><creatorcontrib>FERNANDEZ-ALVAREZ, J</creatorcontrib><creatorcontrib>GOMIS, Ramon</creatorcontrib><creatorcontrib>GUMA, Anna</creatorcontrib><creatorcontrib>VIGUERIE, Nathalie</creatorcontrib><creatorcontrib>CARPENE, Christian</creatorcontrib><creatorcontrib>PALACIN, Manuel</creatorcontrib><title>Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki
Rats
Anna Abella 1 ,
Luc Marti 1 ,
Marta Camps 1 ,
Marc Claret 2 ,
J. Fernández-Alvarez 2 ,
Ramon Gomis 2 ,
Anna Gumà 1 ,
Nathalie Viguerie 3 ,
Christian Carpéné 3 ,
Manuel Palacín 1 ,
Xavier Testar 1 and
Antonio Zorzano 1
1 Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, and Parc Científic de Barcelona,
Barcelona, Spain
2 Endocrinology and Diabetes Unit, IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain
3 Institut National de la Santé et de la Recherche Médicale (INSERM U 317), Toulouse, France
Abstract
In this study we have explored whether the bifunctional protein semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion
protein-1 (VAP-1) represents a novel target for type 2 diabetes. To this end, Goto-Kakizaki (GK) diabetic rats were treated
with the SSAO substrate benzylamine and with low ineffective doses of vanadate previously shown to have antidiabetic effects
in streptozotocin-induced diabetic rats. The administration of benzylamine in combination with vanadate in type 2 diabetic
rats acutely stimulated glucose tolerance, and the chronic treatment normalized hyperglycemia, stimulated glucose transport
in adipocytes, and reversed muscle insulin resistance. Acute in vivo administration of benzylamine and vanadate stimulated
skeletal muscle glucose transport, an effect that was also observed in incubated muscle preparations coincubated with adipose
tissue explants or with human recombinant SSAO. Acute administration of benzylamine/vanadate also ameliorated insulin secretion
in diabetic GK rats, and this effect was also observed in incubated pancreatic islets. In keeping with these observations,
we also demonstrate that pancreatic islets express SSAO/VAP-1. As far as mechanisms of action, we have found that benzylamine/vanadate
causes enhanced tyrosine phosphorylation of proteins and reduced protein tyrosine phosphatase activity in adipocytes. In addition,
incubation of human recombinant SSAO, benzylamine, and vanadate generates peroxovanadium compounds in vitro. Based on these
data, we propose that benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates
insulin secretion and also produces peroxovanadium in adipose tissue, activating glucose metabolism in adipocytes and in neighboring
muscle. This opens the possibility of using the SSAO/VAP-1 activity as a local generator of protein tyrosine phosphatase inhibitors
in antidiabetic therapy.
Footnotes
Address correspondence and reprint requests to Antonio Zorzano, Department de Bioquímica i Biologia Molecular, Facultat de
Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028, Barcelona, Spain. E-mail: azorzano{at}porthos.bio.ub.es
Received for publication 3 December 2002 and accepted in revised form 8 January 2003.
A.A. and L.M. equally contributed to the study.
IAPP, islet amyloid polypeptide; IRS, insulin receptor substrate; LAR, leukocyte antigen-related phosphatase; NMR, nuclear
magnetic resonance; PTP1B, protein tyrosine phosphatase-1B; SHP2, src-homology phosphatase-2; SSAO, semicarbazide-sensitive
amine oxidase; VAP-1, vascular adhesion protein-1.
DIABETES</description><subject>Adipocytes</subject><subject>Adipocytes - metabolism</subject><subject>Amine Oxidase (Copper-Containing) - administration & dosage</subject><subject>Amine Oxidase (Copper-Containing) - genetics</subject><subject>Amine Oxidase (Copper-Containing) - metabolism</subject><subject>Animals</subject><subject>Antidiabetics</subject><subject>Benzylamines - administration & dosage</subject><subject>Biological and medical sciences</subject><subject>Biological Transport - drug effects</subject><subject>Blood Glucose - analysis</subject><subject>Body fat</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Diabetes therapy</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Hyperglycemia</subject><subject>Insulin - metabolism</subject><subject>Insulin - pharmacology</subject><subject>Insulin Resistance</subject><subject>Insulin Secretion</subject><subject>Islets of Langerhans - physiopathology</subject><subject>Kinases</subject><subject>Male</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Musculoskeletal system</subject><subject>Peroxides - metabolism</subject><subject>Phosphatase</subject><subject>Phosphorylation</subject><subject>Phosphotyrosine - metabolism</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Protein Tyrosine Phosphatases - antagonists & inhibitors</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Signal transduction</subject><subject>Type 2 diabetes</subject><subject>Vanadates - administration & dosage</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpt0mGL0zAYB_Aiirc7_QK-kCKcCF53aZI2zcsyzikOJp6K70KaPt1ydsmZpOfuXvjZzdxkTEYoheT3JA8P_yR5kaMxJoRdtlo2EMCPCzym4xwh-igZ5ZzwjGD2_XEyQijHWc44O0lOvb9BCJVxPU1OclyWhDIySn5fw0or6Rr5oFvIrsF4HfQdpPVKG0jna91KD5ffpFdDL11at0vw2pr0k7MBtMnytFaxQIf79GoNLvhUmrQ2QW-70-rveSzQJp3aYLOP8od-iF_6WQb_LHnSyd7D893_LPn67urL5H02m08_TOpZpkrKQgZNQzpWIoUko6QDprqGKURUSXDLJW5IxbqCYKCEF0p1nBVVPM1Vy4qGIE7Oktfbe2-d_TmAD2KlvYK-lwbs4AUjOalQRSN89R-8sYMzsTeB89gLp3Rz28UWLWQPQpvOBifVAgw42VsDnY7bNeeMlgSxyLMjPK52M_tj_s2BjyTAOizk4L2oprMDenGMKtv3sAARZziZH3C85cpZ7x104tbplXT3IkdikynxL1OiwIKKTaZi0cvdSIZmBe2-ZBeiCM53IKZE9p2TRmm_d7TkFWdVdG-3bqkXy1_awf61I8_-AZoo5F0</recordid><startdate>20030401</startdate><enddate>20030401</enddate><creator>ABELLA, Anna</creator><creator>MARTI, Luc</creator><creator>TESTAR, Xavier</creator><creator>ZORZANO, Antonio</creator><creator>CAMPS, Marta</creator><creator>CLARET, Marc</creator><creator>FERNANDEZ-ALVAREZ, J</creator><creator>GOMIS, Ramon</creator><creator>GUMA, Anna</creator><creator>VIGUERIE, Nathalie</creator><creator>CARPENE, Christian</creator><creator>PALACIN, Manuel</creator><general>American Diabetes Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20030401</creationdate><title>Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats</title><author>ABELLA, Anna ; MARTI, Luc ; TESTAR, Xavier ; ZORZANO, Antonio ; CAMPS, Marta ; CLARET, Marc ; FERNANDEZ-ALVAREZ, J ; GOMIS, Ramon ; GUMA, Anna ; VIGUERIE, Nathalie ; CARPENE, Christian ; PALACIN, Manuel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c647t-ebb3f760c0a743fe7cfb7c03c632d9a2b387f532e4395ccf975803c1cd75b3093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adipocytes</topic><topic>Adipocytes - metabolism</topic><topic>Amine Oxidase (Copper-Containing) - administration & dosage</topic><topic>Amine Oxidase (Copper-Containing) - genetics</topic><topic>Amine Oxidase (Copper-Containing) - metabolism</topic><topic>Animals</topic><topic>Antidiabetics</topic><topic>Benzylamines - administration & dosage</topic><topic>Biological and medical sciences</topic><topic>Biological Transport - drug effects</topic><topic>Blood Glucose - analysis</topic><topic>Body fat</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Diabetes therapy</topic><topic>Enzyme Inhibitors - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Hyperglycemia</topic><topic>Insulin - metabolism</topic><topic>Insulin - pharmacology</topic><topic>Insulin Resistance</topic><topic>Insulin Secretion</topic><topic>Islets of Langerhans - physiopathology</topic><topic>Kinases</topic><topic>Male</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Musculoskeletal system</topic><topic>Peroxides - metabolism</topic><topic>Phosphatase</topic><topic>Phosphorylation</topic><topic>Phosphotyrosine - metabolism</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Protein Tyrosine Phosphatases - antagonists & inhibitors</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Signal transduction</topic><topic>Type 2 diabetes</topic><topic>Vanadates - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ABELLA, Anna</creatorcontrib><creatorcontrib>MARTI, Luc</creatorcontrib><creatorcontrib>TESTAR, Xavier</creatorcontrib><creatorcontrib>ZORZANO, Antonio</creatorcontrib><creatorcontrib>CAMPS, Marta</creatorcontrib><creatorcontrib>CLARET, Marc</creatorcontrib><creatorcontrib>FERNANDEZ-ALVAREZ, J</creatorcontrib><creatorcontrib>GOMIS, Ramon</creatorcontrib><creatorcontrib>GUMA, Anna</creatorcontrib><creatorcontrib>VIGUERIE, Nathalie</creatorcontrib><creatorcontrib>CARPENE, Christian</creatorcontrib><creatorcontrib>PALACIN, Manuel</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ABELLA, Anna</au><au>MARTI, Luc</au><au>TESTAR, Xavier</au><au>ZORZANO, Antonio</au><au>CAMPS, Marta</au><au>CLARET, Marc</au><au>FERNANDEZ-ALVAREZ, J</au><au>GOMIS, Ramon</au><au>GUMA, Anna</au><au>VIGUERIE, Nathalie</au><au>CARPENE, Christian</au><au>PALACIN, Manuel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>52</volume><issue>4</issue><spage>1004</spage><epage>1013</epage><pages>1004-1013</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki
Rats
Anna Abella 1 ,
Luc Marti 1 ,
Marta Camps 1 ,
Marc Claret 2 ,
J. Fernández-Alvarez 2 ,
Ramon Gomis 2 ,
Anna Gumà 1 ,
Nathalie Viguerie 3 ,
Christian Carpéné 3 ,
Manuel Palacín 1 ,
Xavier Testar 1 and
Antonio Zorzano 1
1 Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, and Parc Científic de Barcelona,
Barcelona, Spain
2 Endocrinology and Diabetes Unit, IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain
3 Institut National de la Santé et de la Recherche Médicale (INSERM U 317), Toulouse, France
Abstract
In this study we have explored whether the bifunctional protein semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion
protein-1 (VAP-1) represents a novel target for type 2 diabetes. To this end, Goto-Kakizaki (GK) diabetic rats were treated
with the SSAO substrate benzylamine and with low ineffective doses of vanadate previously shown to have antidiabetic effects
in streptozotocin-induced diabetic rats. The administration of benzylamine in combination with vanadate in type 2 diabetic
rats acutely stimulated glucose tolerance, and the chronic treatment normalized hyperglycemia, stimulated glucose transport
in adipocytes, and reversed muscle insulin resistance. Acute in vivo administration of benzylamine and vanadate stimulated
skeletal muscle glucose transport, an effect that was also observed in incubated muscle preparations coincubated with adipose
tissue explants or with human recombinant SSAO. Acute administration of benzylamine/vanadate also ameliorated insulin secretion
in diabetic GK rats, and this effect was also observed in incubated pancreatic islets. In keeping with these observations,
we also demonstrate that pancreatic islets express SSAO/VAP-1. As far as mechanisms of action, we have found that benzylamine/vanadate
causes enhanced tyrosine phosphorylation of proteins and reduced protein tyrosine phosphatase activity in adipocytes. In addition,
incubation of human recombinant SSAO, benzylamine, and vanadate generates peroxovanadium compounds in vitro. Based on these
data, we propose that benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates
insulin secretion and also produces peroxovanadium in adipose tissue, activating glucose metabolism in adipocytes and in neighboring
muscle. This opens the possibility of using the SSAO/VAP-1 activity as a local generator of protein tyrosine phosphatase inhibitors
in antidiabetic therapy.
Footnotes
Address correspondence and reprint requests to Antonio Zorzano, Department de Bioquímica i Biologia Molecular, Facultat de
Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028, Barcelona, Spain. E-mail: azorzano{at}porthos.bio.ub.es
Received for publication 3 December 2002 and accepted in revised form 8 January 2003.
A.A. and L.M. equally contributed to the study.
IAPP, islet amyloid polypeptide; IRS, insulin receptor substrate; LAR, leukocyte antigen-related phosphatase; NMR, nuclear
magnetic resonance; PTP1B, protein tyrosine phosphatase-1B; SHP2, src-homology phosphatase-2; SSAO, semicarbazide-sensitive
amine oxidase; VAP-1, vascular adhesion protein-1.
DIABETES</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>12663473</pmid><doi>10.2337/diabetes.52.4.1004</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2003-04, Vol.52 (4), p.1004-1013 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_pubmed_primary_12663473 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adipocytes Adipocytes - metabolism Amine Oxidase (Copper-Containing) - administration & dosage Amine Oxidase (Copper-Containing) - genetics Amine Oxidase (Copper-Containing) - metabolism Animals Antidiabetics Benzylamines - administration & dosage Biological and medical sciences Biological Transport - drug effects Blood Glucose - analysis Body fat Cell Adhesion Molecules - metabolism Diabetes Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - physiopathology Diabetes therapy Enzyme Inhibitors - metabolism Fundamental and applied biological sciences. Psychology Glucose Glucose - metabolism Hyperglycemia Insulin - metabolism Insulin - pharmacology Insulin Resistance Insulin Secretion Islets of Langerhans - physiopathology Kinases Male Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Musculoskeletal system Peroxides - metabolism Phosphatase Phosphorylation Phosphotyrosine - metabolism Physiological aspects Plasma Protein Tyrosine Phosphatases - antagonists & inhibitors Proteins Rats Rats, Wistar Recombinant Proteins - administration & dosage Signal transduction Type 2 diabetes Vanadates - administration & dosage |
| title | Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats |
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