TMEM16A channel upregulation in arterial smooth muscle cells produces vasoconstriction during diabetes
M. Dennis Leo, Dieniffer Peixoto-Nieves, Wen Yin, Somasundaram Raghavan, Padmapriya Muralidharan, Alejandro Mata‐Daboin, Jonathan H. Jaggar
Abstract
We investigated the involvement of TMEM16A channels in vascular dysfunction during type 2 diabetes (T2D). TMEM16A message, protein, and currents were higher in smooth muscle cells of resistance-size arteries during T2D. Pressure stimulated greater vasoconstriction in the arteries of T2D mice that was abolished in the arteries of TMEM16A smKO mice. Akt2 protein and activity were both lower in T2D arteries, and Akt2 knockdown elevated TMEM16A protein. We propose that a decrease in Akt2 function stimulates TMEM16A expression in arterial smooth muscle cells, leading to vasoconstriction during T2D.
Topics & Concepts
VasoconstrictionDownregulation and upregulationCardiologyInternal medicineDiabetes mellitusMedicineSmooth muscleEndocrinologyChemistryGeneBiochemistryNitric Oxide and Endothelin EffectsApelin-related biomedical researchMuscle Physiology and Disorders