Metformin, an AMPK activator, stimulates the phosphorylation of Aquaporin 2 and Urea Transporter A1 in Inner Medullary Collecting Ducts.

Metformin, an AMPK activator, stimulates the phosphorylation of Aquaporin 2 and Urea Transporter A1 in Inner Medullary Collecting Ducts. Am J Physiol Renal Physiol. 2016 Mar 9;:ajprenal.00102.2016 Authors: Klein JD, Wang Y, Blount MA, Molina PA, LaRocque LM, Ruiz JA, Sands JM Abstract Nephrogenic diabetes insipidus (NDI) is characterized by production of very large quantities of dilute urine due to an inability of the kidney to respond to vasopressin. Congenital NDI results from mutations in the type 2 vasopressin receptor (V2R) in approximately 90% of families. These patients do not have mutations in aquaporin-2 (AQP2) or urea transporter UT-A1 (UT-A1). We tested adenosine monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter). We found AMPK expressed in rat inner medulla (IM). AMPK directly phosphorylated AQP2 and UT-A1 in vitro. Metformin, an AMPK activator, increased phosphorylation of both AQP2 and UT-A1 in rat inner medullary collecting ducts (IMCDs). Metformin increased the apical plasma membrane accumulation of AQP2, but not UT-A1, in rat IM. Metformin increased both osmotic water permeability and urea permeability in perfused rat terminal IMCDs. These findings suggest that metformin increases osmotic water permeability by increasing AQP2 accumulation in the apical plasma membrane but increases urea permeability by activating UT-A1 already prese...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research