The Role of Angiotensin II in Skeletal Muscle Metabolism

Abstract

Hypertension and diabetes have long been closely linked. As such, the major player in the renin, angiotensin system, angiotensin II, has recently been investigated for its effects on metabolism and diabetes. Since skeletal muscle is one of the most metabolically active tissues, this study investigates the effects of angiotensin II specifically on skeletal muscle. In this study, L6 skeletal muscle cells were treated with angiotensin II for either 3 or 24 hours and a number of effects were investigated. Fatty acid oxidation and lipid synthesis was measured using [1-14C]-palmitate, glucose oxidation and glycogen synthesis were measured using 14C-glucose. In addition,mitochondrial oxidative capacity was measured using an XF 24 Flux Analyzer (Seahorse Bioscience) and reactive oxygen species measured using confocal microscopy. The clinical study involving the drug Benicar ® investigated the metabolic effects of blocking angiotensin II on skeletal muscle fatty acid oxidation, glucose oxidation, and oxidative and glycolytic enzyme activity. In L6 cells, angiotensin II significantly reduced fatty acid oxidation after 24 hours (p<0.01) and 3 hours (p<0.001) if angiotensin II was present during oxidation experiments. It also significantly reduced mitochondrial oxidative capacity (p<0.05) after 24 hours and significantly increased reactive oxygen species production (p<0.05) over 3 hours. The clinical study showed no significant effects of Benicar® on fatty acid or glucose oxidation or any enzyme activities.