Protein- and diabetes-induced glomerular hyperfiltration: role of glucagon, vasopressin, and urea

Am J Physiol Renal Physiol. 2015 Jul 1;309(1):F2-23. doi: 10.1152/ajprenal.00614.2014. Epub 2015 Apr 29.


A single protein-rich meal (or an infusion of amino acids) is known to increase the glomerular filtration rate (GFR) for a few hours, a phenomenon known as "hyperfiltration." It is important to understand the factors that initiate this upregulation because it becomes maladaptive in the long term. Several mediators and paracrine factors have been shown to participate in this upregulation, but they are not directly triggered by protein intake. Here, we explain how a rise in glucagon and in vasopressin secretion, directly induced by protein ingestion, might be the initial factors triggering the hepatic and renal events leading to an increase in the GFR. Their effects include metabolic actions in the liver and stimulation of sodium chloride reabsorption in the thick ascending limb. Glucagon is not only a glucoregulatory hormone. It is also important for the excretion of nitrogen end products by stimulating both urea synthesis in the liver (along with gluconeogenesis from amino acids) and urea excretion by the kidney. Vasopressin allows the concentration of nitrogenous end products (urea, ammonia, etc.) and other protein-associated wastes in a hyperosmotic urine, thus allowing a very significant water economy characteristic of all terrestrial mammals. No hyperfiltration occurs in the absence of one or the other hormone. Experimental results suggest that the combined actions of these two hormones, along with the complex intrarenal handling of urea, lead to alter the composition of the tubular fluid at the macula densa and to reduce the intensity of the signal activating the tubuloglomerular feedback control of GFR, thus allowing GFR to raise. Altogether, glucagon, vasopressin, and urea contribute to set up the best compromise between efficient urea excretion and water economy.

Keywords: amino acid; nitrogen excretion; thick ascending limb; tubuloglomerular feedback; urine concentration.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclic AMP / metabolism
  • Dietary Proteins / metabolism*
  • Glomerular Filtration Rate
  • Glucagon / physiology*
  • Humans
  • Kidney Glomerulus / physiology*
  • Liver / metabolism
  • Nitrogen / metabolism
  • Urea / metabolism*
  • Vasopressins / physiology*
  • Water / metabolism


  • Dietary Proteins
  • Water
  • Vasopressins
  • Urea
  • Glucagon
  • Cyclic AMP
  • Nitrogen