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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1

Texto completo
Crajoinas, Renato O. [1] ; Oricchio, Felipe T. [1] ; Pessoa, Thaissa D. [2] ; Pacheco, Bruna P. M. [1] ; Lessa, Lucilia M. A. [2] ; Malnic, Gerhard [2] ; Girardi, Adriana C. C. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, BR-05403900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05403900 Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Citações Web of Science: 117

Crajoinas RO, Oricchio FT, Pessoa TD, Pacheco BP, Lessa LM, Malnic G, Girardi AC. Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1. Am J Physiol Renal Physiol 301: F355-F363, 2011. First published May 18, 2011; doi: 10.1152/ajprenal.00729.2010.-Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone considered a promising therapeutic agent for type 2 diabetes because it stimulates beta cell proliferation and insulin secretion in a glucose-dependent manner. Cumulative evidence supports a role for GLP-1 in modulating renal function; however, the mechanisms by which GLP-1 induces diuresis and natriuresis have not been completely established. This study aimed to define the cellular and molecular mechanisms mediating the renal effects of GLP-1. GLP-1 (1 mu g.kg(-1).min(-1)) was intravenously administered in rats for the period of 60 min. GLP-1-infused rats displayed increased urine flow, fractional excretion of sodium, potassium, and bicarbonate compared with those rats that received vehicle (1% BSA/saline). GLP-1-induced diuresis and natriuresis were also accompanied by increases in renal plasma flow and glomerular filtration rate. Real-time RT-PCR in microdissected rat nephron segments revealed that GLP-1 receptor-mRNA expression was restricted to glomerulus and proximal convoluted tubule. In rat renal proximal tubule, GLP-1 significantly reduced Na+/H+ exchanger isoform 3 (NHE3)-mediated bicarbonate reabsorption via a protein kinase A (PKA)-dependent mechanism. Reduced proximal tubular bicarbonate flux rate was associated with a significant increase of NHE3 phosphorylation at the PKA consensus sites in microvillus membrane vesicles. Taken together, these data suggest that GLP-1 has diuretic and natriuretic effects that are mediated by changes in renal hemodynamics and by downregulation of NHE3 activity in the renal proximal tubule. Moreover, our findings support the view that GLP-1-based agents may have a potential therapeutic use not only as antidiabetic drugs but also in hypertension and other disorders of sodium retention. (AU)

Processo FAPESP: 07/52945-8 - Importância do peptídeo semelhante ao glucagon 1 (GLP-1) na manutenção do volume extracelular: abordagem funcional, farmacológica e molecular
Beneficiário:Adriana Castello Costa Girardi
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 09/50467-7 - Transporte de íons em células renais e sua regulação
Beneficiário:Gerhard Malnic
Linha de fomento: Auxílio à Pesquisa - Regular