Glimepiride induces the PI3 kinase (PI3K) and Akt pathway, along with insulin receptor substrate-1/2 and endothelial nitric oxide synthase. Glimepiride also increases osteoblast proliferation and differentiation, which is thought to be related to its ability to activate the PI3K and Akt pathway. Furthermore, Glimepiride enhances intrinsic peroxisome proliferator-activated receptor γ activity. Glimepiride also increases protein expression of glucose transports 1 and 4, and is a potent KIR channel blocker. Potent Kir6 (KATP) channel blocker and anti-diabetic agent. Inhibits pinacidil-activated cardiac Kir6 channels with an IC50 of 6.8 nM.
Lawrence et al. Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sacrolemmal KATP channels. Br.J.Pharmacol. 2002, 136, (5), 746-52.
SE Nissen.; SJ Nicholls.; K Wolski.; R Nesto.; S Kupfer. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the periscope randomized controlled . JAMA. 2008, 299, (13), 1561-1573.