Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1
Autor: | Adriana C. C. Girardi, Renato O. Crajoinas, Thaissa Dantas Pessoa, Bruna Piccolo Muniz Pacheco, G Malnic, Lucilia Maria Abreu Lessa, Felipe Theocarides Oricchio |
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Rok vydání: | 2011 |
Předmět: |
endocrine system
medicine.medical_specialty Sodium-Hydrogen Exchangers Physiology Type 2 diabetes Kidney Glucagon-Like Peptide-1 Receptor Glucagon-Like Peptide 1 Internal medicine Cyclic AMP Receptors Glucagon medicine Animals Hypoglycemic Agents Phosphorylation Rats Wistar Pentanoic Acids Receptor Protein kinase A Sodium-Hydrogen Exchanger 3 Venoms Chemistry digestive oral and skin physiology Kidney metabolism medicine.disease Cyclic AMP-Dependent Protein Kinases Glucagon-like peptide-1 Rats Endocrinology Renal physiology Exenatide Thiazolidines Natriuretic Agents Beta cell Peptides medicine.drug |
Zdroj: | American Journal of Physiology-Renal Physiology. 301:F355-F363 |
ISSN: | 1522-1466 1931-857X |
Popis: | 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 μg·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. |
Databáze: | OpenAIRE |
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