Regulation of mitochondrial dynamics and energetics in the diabetic renal proximal tubule by the β2-adrenergic receptor agonist formoterol.

Regulation of mitochondrial dynamics and energetics in the diabetic renal proximal tubule by the β2-adrenergic receptor agonist formoterol. Am J Physiol Renal Physiol. 2020 Sep 21;: Authors: Cleveland KH, Brosius FC, Schnellmann RG Abstract Diabetes is a prevalent metabolic disease that contributes to ~50% of all end stage renal diseases (ESRD) and has limited treatment options. We previously demonstrated that the β2-adrenergic receptor (AR) agonist formoterol induced mitochondrial biogenesis and promoted recovery from acute kidney injury. Here, we assessed the effects of formoterol on mitochondrial dysfunction and dynamics in renal proximal tubule cells (RPTC) treated with high glucose and in a mouse model of type 2 diabetes. RPTC exposed to glucose exhibited increased electron transport chain (ETC) complex I, II, III and V protein levels, reduced ATP levels and uncoupled oxygen consumption rate (OCR) compared to RPTC cultured in the absence of glucose or osmotic controls. ETC proteins, ATP and OCR were restored in RPTC treated with formoterol.High-glucose RPTC exhibited an increase in phospho-Drp1, a mitochondrial fission protein, and a decrease in Mfn1, a mitochondrial fusion protein. Diabetic db/db and non-diabetic db/m mice were treated with formoterol or vehicle for 3 weeks and euthanized. Db/db mice showed increased renal cortical ETC protein levels in complexes I, III and V and decreased ATP and these changes were prevented...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research