Dipeptidyl peptidase IV inhibition upregulates GLUT4 translocation and expression in heart and skeletal muscle of spontaneously hypertensive rats

Imagem de Miniatura
Arquivos
art_CRAJOINAS_Dipeptidyl_peptidase_IV_inhibition_upregulates_GLUT4_translocation_and_2013.PDF (1.5 MB)
Citações na Scopus
58
Tipo de produção
article
Data de publicação
2013
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE BV
Autores
GIANNOCCO, Gisele
OLIVEIRA, Kelen C.
MACIEL, Rui M. B.
Citação
EUROPEAN JOURNAL OF PHARMACOLOGY, v.698, n.1-3, p.74-86, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The purpose of the current study was to test the hypothesis that the dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin, which exerts anti-hyperglycemic and anti-hypertensive effects, upregulates GLUT4 translocation, protein levels, and/or mRNA expression in heart and skeletal muscle of spontaneously hypertensive rats (SHRs). Ten days of treatment with sitagliptin (40 mg/kg twice daily) decreased plasma DPPIV activity in both young (Y, 5-week-old) and adult (A, 20-week-old) SHRs to similar extents ( similar to 85%). However, DPPIV inhibition only lowered blood pressure in Y-SHRs (119 +/- 3 vs. 136 +/- 4 mmHg). GLUT4 translocation, total protein levels and mRNA expression were decreased in the heart, soleus and gastrocnemius muscle of SHRs compared to age-matched Wistar Kyoto (WKY) normotensive rats. These differences were much more pronounced between A-SHRs and A-WKY rats than between Y-SHRs and Y-WKY rats. In Y-SHRs, sitagliptin normalized GLUT4 expression in the heart, soleus and gastrocnemius. In A-SHRs, sitagliptin increased GLUT4 expression to levels that were even higher than those of A-WKY rats. Sitagliptin enhanced the circulating levels of the DPPIV substrate glucagon-like peptide-1 (GLP-1) in SHRs. In addition, stimulation of the GLP-1 receptor in cardiomyocytes isolated from SHRs increased the protein level of GLUT4 by 154 +/- 13%. Collectively, these results indicate that DPPIV inhibition upregulates GLUT4 in heart and skeletal muscle of SHRs. The underlying mechanism of sitagliptin-induced upregulation of GLUT4 in SHRs may be, at least partially, attributed to GLP-1.
Palavras-chave
Dipeptidyl peptidase IV, Glucose transporter type 4, Hypertension, Heart, Skeletal muscle
URI
https://observatorio.fm.usp.br/handle/OPI/2372
Referências
  1. Ahrén Bo, 2003, Curr Diab Rep, V3, P365, DOI 10.1007/s11892-003-0079-9
  2. Barreto-Chaves MLM, 2000, BRAZ J MED BIOL RES, V33, P661, DOI 10.1590/S0100-879X2000000600007
  3. Brandt I, 2006, CLIN CHEM, V52, P82, DOI 10.1373/clinchem.2005.057638
  4. BUCHANAN TA, 1992, DIABETES, V41, P872, DOI 10.2337/diabetes.41.7.872
  5. CAMPBELL IW, 1995, BIOCHEM BIOPH RES CO, V211, P780, DOI 10.1006/bbrc.1995.1881
  6. CHEN C, 1994, J CLIN INVEST, V94, P399, DOI 10.1172/JCI117335
  7. Conarello SL, 2003, P NATL ACAD SCI USA, V100, P6825, DOI 10.1073/pnas.0631828100
  8. Crajoinas RO, 2010, AM J PHYSIOL-RENAL, V299, pF872, DOI 10.1152/ajprenal.00654.2009
  9. De Cingolani GEC, 2004, METABOLISM, V53, P382, DOI 10.1016/j.metabol.2003.10.017
  10. Ding S.Y., 2001, J BIOL CHEM, V286, P16768
  11. Drucker DJ, 2003, EXPERT OPIN INV DRUG, V12, P87, DOI 10.1517/13543784.12.1.87
  12. Drucker DJ, 2006, LANCET, V368, P1696, DOI 10.1016/S0140-6736(06)69705-5
  13. Girardi ACC, 2012, AM J PHYSIOL-CELL PH, V302, pC1569, DOI 10.1152/ajpcell.00017.2012
  14. Gronborg M, 2002, MOL CELL PROTEOMICS, V1, P517, DOI 10.1074/mcp.M200010-MCP200
  15. Holst JJ, 2007, PHYSIOL REV, V87, P1409, DOI 10.1152/physrev.00034.2006
  16. Vyas AK, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0017178
  17. Jackson EK, 2008, HYPERTENSION, V51, P1637, DOI 10.1161/HYPERTENSIONAHA.108.112532
  18. JAMES DE, 1985, AM J PHYSIOL, V248, pE567
  19. JAMES DE, 1988, NATURE, V333, P183, DOI 10.1038/333183a0
  20. KATAYAMA S, 1994, HYPERTENSION, V23, P1071
  21. Katayama S, 1997, Hypertens Res, V20, P279, DOI 10.1291/hypres.20.279
  22. Lambeir AM, 2003, CRIT REV CL LAB SCI, V40, P209, DOI 10.1080/713609354
  23. Lauritzen HPMM, 2010, AM J PHYSIOL-ENDOC M, V299, pE169, DOI 10.1152/ajpendo.00066.2010
  24. LEE MK, 1994, DIABETES, V43, P1435, DOI 10.2337/diabetes.43.12.1435
  25. Lehnen AM, 2011, HORM METAB RES, V43, P231, DOI 10.1055/s-0031-1271747
  26. LOWRY OH, 1951, J BIOL CHEM, V193, P265
  27. Marguet D, 2000, P NATL ACAD SCI USA, V97, P6874, DOI 10.1073/pnas.120069197
  28. MENTLEIN R, 1993, EUR J BIOCHEM, V214, P829, DOI 10.1111/j.1432-1033.1993.tb17986.x
  29. MENTLEIN R, 1993, REGUL PEPTIDES, V49, P133, DOI 10.1016/0167-0115(93)90435-B
  30. Mistry GC, 2008, J CLIN PHARMACOL, V48, P592, DOI 10.1177/0091270008316885
  31. Okerson T., 2011, AM J HYPERTENS, V23, P334
  32. Pacheco BPM, 2011, J HYPERTENS, V29, P520, DOI 10.1097/HJH.0b013e328341939d
  33. PALMIERI FE, 1983, BIOCHIM BIOPHYS ACTA, V755, P522, DOI 10.1016/0304-4165(83)90259-3
  34. PATERNOSTRO G, 1995, CARDIOVASC RES, V30, P205, DOI 10.1016/S0008-6363(95)00019-4
  35. REAVEN GM, 1989, DIABETES, V38, P1155, DOI 10.2337/diabetes.38.9.1155
  36. Shioda T, 1998, P NATL ACAD SCI USA, V95, P6331, DOI 10.1073/pnas.95.11.6331
  37. Tanaka T, 2011, CURR OPIN NEPHROL HY, V20, P476, DOI 10.1097/MNH.0b013e328349af9d
  38. THORENS B, 1990, DIABETES CARE, V13, P209, DOI 10.2337/diacare.13.3.209
  39. Villanueva-Penacarrillo ML, 2001, ENDOCRINE, V15, P241, DOI 10.1385/ENDO:15:2:241
  40. YOSHIOKA S, 1993, METABOLISM, V42, P75, DOI 10.1016/0026-0495(93)90175-N

Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13
Artigos e Materiais de Revistas Científicas - ODS/03