The incretin hormone, glucagon-like peptide 1 (GLP1), is released from the gut in response to fat or carbohydrate and contributes to negative feedback control of blood glucose by effects on insulin secretion, glucagon, and gastric emptying. GLP1 receptors are also expressed in proximal tubule, and possibly elsewhere in the kidney. We examined the effect of a GLP1 receptor agonist on single nephron GFR (SNGFR), proximal reabsorption (Jprox), tubuloglomerular feedback (TGF) responses, and urine flow rate in hydropenic male Wistar and Wistar Froemter rats. Methods- Micropuncture and whole-kidney data were obtained before and during infusion of GLP1 agonist, exenatide (1 nmol/h iv). SNGFR and Jprox were measured by late proximal collection at both extremes of TGF activation. Primary changes in Jprox were revealed by analysis of covariance for Jprox with SNGFR as covariate. Effects on TGF activation were determined in separate experiments by comparing early distal and late proximal collections. Results and Conclusion- Exenatide increased SNGFR by 33-50%, suppressed proximal tubular reabsorption by 20-40%, doubled early distal flow rate, and increased urine flow rate 6-fold without altering the efficiency of glomerulotubular balance, TGF responsiveness, or the tonic influence of TGF. This implies that exenatide is both a proximal diuretic and a renal vasodilator. Since the natural agonist for the GLP1 receptor is regulated by intake of fat and carbohydrate, but not by salt or fluid, the control of salt excretion by the GLP-1R system departs from the usual negative-feedback paradigm for hormonal regulation of salt balance.
- Glucagon-like peptide 1
- glomerular filtration
- tubular reabsorption
- tubuloglomerular feedback
- Copyright © 2012, American Journal of Physiology - Renal Physiology