RESEARCH PROJECT

Insulin signaling and renal epithelial transport

Epithelial cells that line the renal proximal tubule reabsorb a significant fraction of filtered sodium and water, and therefore, play a key role in regulating body fluid osmotic homeostasis.  The sodium proton exchanger 3 (NHE3) is expressed in the proximal tubule and accounts for the majority of total Na+and water epithelial transport.  Any changes in NHE3 activity can greatly impact body fluid osmotic homeostasis and alter cellular functions.  Thus, NHE3 is a tightly regulated transport protein. Similar to NHE3, insulin receptors are expressed along the renal tubule of the mammalian kidney with a higher density in the proximal tubule.  Importantly, insulin was shown to stimulate Na+and water epithelial transport in this segment via increased NHE3 activity.  However, despite extensive research efforts, little is known about how insulin activates NHE3. Our laboratory uses the zebrafish as a model organism to study the signaling mechanisms that link insulin to an increase in proximal tubule-specific sodium proton exchanger 3 activity.