Role fo AMP-activated protein kinase (AMPK) in diabetic nephropathy: change of tubuloglomerular feeedback and salt transport

• Applicant: Danyang Huang, Ph.D.
• Subject Area: Pharmacology
• Term: from 2006 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 31086667

AMP-activated protein kinase (AMPK) is a serine-threonine kinase that regulates many metabolic pathways including fatty acid ß-oxidation, cholesterol synthesis, glycolysis and glucose transport in heart and skeletal muscle. AMPK is considered as a energy sensor kinase since it is activated in a very sensitive manner by cellular stress that depletes ATP or increases AMP/ATP ratio. The role of AMPK in mamalian kidney is unknown. Immunohistochemical and immunofluorescence staining confirmed strong expression of activated AMPK in the apical membrance of cortical thick acending limb and macula densa cells as well as basolateral surface of the collecting duct cells of rat kidney. Furthermore, AMPK activity was increased by 25% in rats treated with high salt diet and a transient activation of AMPK was observed in a macula densa cell line in response to changes in osmolality suggesting a role for this kinase in the control of tubular salt reabsorption and tubuloglomerular feedback response. The aim of this project is to clarify the role of AMPK in control of renal hemodynamics, tubular salt transport and tubuloglomerular feedback. To this end, we will perform pharmacological inhibition or activation of AMPK in clearance and micropuncture experiments in rats and transgenic mice in vivo combined with analysis of renal AMPK expression.

• DFG Programme: Research Grants