Renin inhibition improved muscular function by alleviating insulin resistance and AGEs/RAGE signaling in skeletal muscle associated with high glucose: Exploration of renin inhibitor tanshinone IIA.

Diabeticsarcopenia (DS) is a key complication in skeletal muscle associated with hyperglycemia. This study aimed to clarify the role of tissue renin-angiotensin system (RAS) in DS and to explore novel renin inhibitor to preserve muscle associated with diabetes. A case-control study was performed to assess angiotensin II (Ang II) level in diabetes participants with/without sarcopenia. The docking analysis, the molecular dynamics simulation, and the surface plasmon resonance as well as the human renin-transfected HEK-293 cells and the mouse myoblasts C2C12 were employed to evaluate the binding of tanshinone IIA (Tan IIA) with renin protein and the subsequent bioactivity. The db/db mice were orally administered with Tan IIA sulfonate for 8 weeks and the C2C12 cells culturing with high glucose (HG, 30 mM) were treated with Tan IIA. The DS participants displayed significant elevation in serum Ang II level. Consistently, high glucose induced up-regulation in protein expression of renin and its downstream active peptide Ang II in C2C12 myoblasts. Tan IIA exhibited direct binding affinity with renin protein, showed the comparable IC