Effects of peroxisome proliferator-activated receptor [gamma] agonists on Na+ transport and activity of the kinase SGK1 in epithelial cells from lung and kidney
Background and purpose: Peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) agonists, such as rosiglitazone and pioglitazone, sensitize cells to insulin, and are therefore used to treat type 2 diabetes. However, in some patients, these drugs induce oedema, and the present study tests th...
Saved in:
Published in | British journal of pharmacology Vol. 159; no. 3; p. 678 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Blackwell Publishing Ltd
01.02.2010
|
Online Access | Get full text |
Cover
Loading…
Abstract | Background and purpose: Peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) agonists, such as rosiglitazone and pioglitazone, sensitize cells to insulin, and are therefore used to treat type 2 diabetes. However, in some patients, these drugs induce oedema, and the present study tests the hypothesis that this side effect reflects serum and glucocorticoid-inducible kinase 1 (SGK1)-dependent enhancement of epithelia Na+ absorption. Experimental approach: Na+ absorbing epithelial cells (H441 cells, mpkCCD cells) on permeable membranes were mounted in Ussing chambers, and the effects of rosiglitazone (2 µM) and pioglitazone (10 µM) on transepithelial Na+ absorption were quantified electrometrically. Changes in SGK1 activity were assessed by monitoring phosphorylation of residues within an endogenous protein. Key results: Both cell types absorbed Na+ via an electrogenic process that was enhanced by insulin. In mpkCCD cells, this stimulation of Na+ transport was associated with increased activity of SGK1, whereas insulin regulated Na+ transport in H441 cells through a mechanism that did not involve activation of this kinase. Rosiglitazone and pioglitazone had no discernible effect on transepithelial Na+ absorption in unstimulated or insulin-stimulated cells and failed to alter cellular SGK1 activity. Conclusions and implications: Our results do not support the view that PPAR[gamma] agonists stimulate epithelial Na+ absorption or alter the control of cellular SGK1 activity. It is therefore likely that other mechanisms are involved in PPAR[gamma]-mediated fluid retention, and a better understanding of these mechanisms may help with the identification of patients likely to develop oedema or heart failure when treated with these drugs. [PUBLICATION ABSTRACT] |
---|---|
AbstractList | Background and purpose: Peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) agonists, such as rosiglitazone and pioglitazone, sensitize cells to insulin, and are therefore used to treat type 2 diabetes. However, in some patients, these drugs induce oedema, and the present study tests the hypothesis that this side effect reflects serum and glucocorticoid-inducible kinase 1 (SGK1)-dependent enhancement of epithelia Na+ absorption. Experimental approach: Na+ absorbing epithelial cells (H441 cells, mpkCCD cells) on permeable membranes were mounted in Ussing chambers, and the effects of rosiglitazone (2 µM) and pioglitazone (10 µM) on transepithelial Na+ absorption were quantified electrometrically. Changes in SGK1 activity were assessed by monitoring phosphorylation of residues within an endogenous protein. Key results: Both cell types absorbed Na+ via an electrogenic process that was enhanced by insulin. In mpkCCD cells, this stimulation of Na+ transport was associated with increased activity of SGK1, whereas insulin regulated Na+ transport in H441 cells through a mechanism that did not involve activation of this kinase. Rosiglitazone and pioglitazone had no discernible effect on transepithelial Na+ absorption in unstimulated or insulin-stimulated cells and failed to alter cellular SGK1 activity. Conclusions and implications: Our results do not support the view that PPAR[gamma] agonists stimulate epithelial Na+ absorption or alter the control of cellular SGK1 activity. It is therefore likely that other mechanisms are involved in PPAR[gamma]-mediated fluid retention, and a better understanding of these mechanisms may help with the identification of patients likely to develop oedema or heart failure when treated with these drugs. [PUBLICATION ABSTRACT] |
Author | Mansley, Morag K Inglis, Sarah K Wilson, Stuart M Hansen, Michael K Getty, Jennet Husband, Elaine M |
Author_xml | – sequence: 1 givenname: Stuart M surname: Wilson fullname: Wilson, Stuart M – sequence: 2 givenname: Morag K surname: Mansley fullname: Mansley, Morag K – sequence: 3 givenname: Jennet surname: Getty fullname: Getty, Jennet – sequence: 4 givenname: Elaine M surname: Husband fullname: Husband, Elaine M – sequence: 5 givenname: Sarah K surname: Inglis fullname: Inglis, Sarah K – sequence: 6 givenname: Michael K surname: Hansen fullname: Hansen, Michael K |
BookMark | eNqNjk1LAzEQhoNUcFv9DwMeZdfE7pdnqQoFL3orUobdyZptNlmTrLT_xp9qWsSzcxl4n3mGd85mxhpiDATPRJzbPhN5VabFshbZHef3GedFmWf7M5b8gRlLOOdVKkRdX7C59z3nEVZFwr5XUlITPFgJIzm7V94OBKOzWklyGKxLsQnqCwO14KihMUaw6XAY8B2ws0b5o27gBW8gODR-tC4AmhZOogqH4_PwQbBTBj3B69NagDJAo4qpVqihIa09SGcH0JPpTvZOtYYOl-xcovZ09bsX7Ppx9fbwnMaKnxP5sO3t5ExEW1HkRSVqXlbL_139ABgqZo4 |
ContentType | Journal Article |
Copyright | 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society |
Copyright_xml | – notice: 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society |
DBID | 7QP 7TK K9. NAPCQ |
DOI | 10.1111/j.1476-5381.2009.00564.x |
DatabaseName | Calcium & Calcified Tissue Abstracts Neurosciences Abstracts ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium |
DatabaseTitle | Nursing & Allied Health Premium ProQuest Health & Medical Complete (Alumni) Calcium & Calcified Tissue Abstracts Neurosciences Abstracts |
DatabaseTitleList | Nursing & Allied Health Premium |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Pharmacy, Therapeutics, & Pharmacology |
EISSN | 1476-5381 |
ExternalDocumentID | 3376031141 |
GroupedDBID | --- .3N 05W 0R~ 1OC 23N 24P 2WC 33P 36B 3SF 4.4 52U 52V 5GY 6J9 7QP 7TK 8-0 8-1 8UM A00 AAESR AAEVG AAHHS AANLZ AAONW AASGY AAXRX AAZKR ABCUV ABDBF ABPVW ABQWH ABXGK ACAHQ ACCFJ ACCZN ACFBH ACGFO ACGFS ACGOF ACMXC ACPOU ACPRK ACXBN ACXQS ADBBV ADBTR ADEOM ADIZJ ADKYN ADMGS ADOZA ADXAS ADZMN ADZOD AEEZP AEGXH AEIGN AEIMD AENEX AEQDE AEUQT AEUYR AFBPY AFFPM AFGKR AFPWT AFRAH AFZJQ AHBTC AHMBA AIACR AIAGR AITYG AIURR AIWBW AJBDE ALAGY ALIPV ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMYDB AOIJS ATUGU AZBYB AZVAB B0M BAFTC BAWUL BFHJK BHBCM BMXJE BRXPI C45 CAG COF CS3 DCZOG DIK DRFUL DRMAN DRSTM DU5 E3Z EAD EAP EAS EBC EBD EBS ECV EJD EMB EMK EMOBN ENC ESX F5P FUBAC G-S GODZA GX1 H.X HGLYW HYE HZ~ K9. KBYEO LATKE LEEKS LH4 LITHE LOXES LSO LUTES LW6 LYRES MEWTI MK0 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM MY~ N9A NAPCQ NF~ O66 O9- OIG OK1 OVD P2P P2W P4E Q.N QB0 ROL RPM RWI SJN SUPJJ SV3 TEORI TR2 TUS UPT WBKPD WH7 WHWMO WIH WIJ WIK WIN WOHZO WVDHM WXSBR XV2 YHG ZGI ZZTAW ~8M ~S- |
ID | FETCH-proquest_journals_15457180673 |
ISSN | 0007-1188 |
IngestDate | Fri Sep 13 07:37:27 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 3 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-proquest_journals_15457180673 |
PQID | 1545718067 |
PQPubID | 42104 |
ParticipantIDs | proquest_journals_1545718067 |
PublicationCentury | 2000 |
PublicationDate | 20100201 |
PublicationDateYYYYMMDD | 2010-02-01 |
PublicationDate_xml | – month: 02 year: 2010 text: 20100201 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | London |
PublicationPlace_xml | – name: London |
PublicationTitle | British journal of pharmacology |
PublicationYear | 2010 |
Publisher | Blackwell Publishing Ltd |
Publisher_xml | – name: Blackwell Publishing Ltd |
SSID | ssj0014775 |
Score | 3.9564614 |
Snippet | Background and purpose: Peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) agonists, such as rosiglitazone and pioglitazone, sensitize cells to... |
SourceID | proquest |
SourceType | Aggregation Database |
StartPage | 678 |
Title | Effects of peroxisome proliferator-activated receptor [gamma] agonists on Na+ transport and activity of the kinase SGK1 in epithelial cells from lung and kidney |
URI | https://www.proquest.com/docview/1545718067/abstract/ |
Volume | 159 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1La9tAEF5Mesml9JHSNg8G0uTiqCBHD-uYNM7bbiAKGEoxWntlRGzJVHJo-2vyN3PLzO7KKyfGNL0II-FFYj5mZ76d-YaxL30ROHy_4VocHaTlDGxuRZHjWXEfY92GaHLOiRpod7zTG-e863ZrtYdK1dK04F_7fxf2lfyPVfEe2pW6ZF9g2dmieAN_o33xihbG6z_ZuGWKMUjv-3eSZ2NqfMpGVLBC6bRFfQt3EYWV6NrEpKB5Gu7hMBqPox33qB4NM5LOlWcGHYwjD2lmhFI7VzKufT1dQpcS3CYpbnv165MLW4qNTKilY0SsO50A5KpbZTTVjY-3ySB9cm6sNZQqghUTI55t6P2ZiOR1QVWnhrNt49tpmr2N6B0amvZEFGrAwblsNTJ4zbku3myNIoqp21Wmgw7p56pGnjCaiqEztU_KvfsWZkzKoQvl0R3fs9Cr23MuX6uQJ1VKQDpwTw0UWrKx6OVKqVPXc8qC06qWd-d77_jm8rIXtrrh_FMVO1At0j7mopi4v2r4gUu8wdHZxewAzPF9NXxDf9F8EdrCl3gWTcgQKXzDXuvcBg4UUN-ymkjfsd0rZd8_exCaXr98D3bhqmL59-xeoxmyGAyaYTGaoUQz_JBY_gklkiFLoRPVYYZjQOtDiWNaHBELCsdAOIYkBYNjkDgGwjEQjuW_FY7X2PZxK_x2apXf39MoznuUIWD4ReOYPrCVNEvFRwYu7unN2B00bI7pQjMIfM692IvFwOdxYDuf2MaylT4vf7zOVg16N9hK8WsqNjFyLfiWtPEjDJaldw |
link.rule.ids | 315,786,790,27957,27958 |
linkProvider | Flying Publisher |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Effects+of+peroxisome+proliferator-activated+receptor+%5Bgamma%5D+agonists+on+Na%2B+transport+and+activity+of+the+kinase+SGK1+in+epithelial+cells+from+lung+and+kidney&rft.jtitle=British+journal+of+pharmacology&rft.au=Wilson%2C+Stuart+M&rft.au=Mansley%2C+Morag+K&rft.au=Getty%2C+Jennet&rft.au=Husband%2C+Elaine+M&rft.date=2010-02-01&rft.pub=Blackwell+Publishing+Ltd&rft.issn=0007-1188&rft.eissn=1476-5381&rft.volume=159&rft.issue=3&rft.spage=678&rft_id=info:doi/10.1111%2Fj.1476-5381.2009.00564.x&rft.externalDBID=NO_FULL_TEXT&rft.externalDocID=3376031141 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0007-1188&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0007-1188&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0007-1188&client=summon |