Gliclazide-d4

Gliclazide-d₄ is intended for use as an internal standard for the quantification of gliclazide by GC- or LC-MS. Gliclazide is a sulfonylurea and an inhibitor of pancreatic β-cell ATP-sensitive potassium (K_ATP) channels (IC₅₀ = 184 nM for murine β-cells).^1,2 It is selective for pancreatic β-cell over cardiac and arterial smooth muscle cell K_ATP channels (IC₅₀s = 19.5 and 37.9 μM, respectively).¹ Gliclazide (5 μM) increases insulin-induced glucose uptake and glucose transporter 4 (GLUT4) translocation to the plasma membrane in a differentiated 3T3L1 adipocyte model of insulin resistance induced by hydrogen peroxide.³ Gliclazide (5 and 10 μg/ml) reduces LDL oxidation by human aortic smooth muscle cells (HASMCs), decreasing TBARS content and 8-isoprostane levels.⁴ It also decreases oxidized LDL-induced HASMC proliferation and monocyte adhesion when used at concentrations ranging from 1 to 10 μg/ml. Gliclazide (5 mg/kg) reduces serum glucose levels and increases glucose uptake by isolated rat hindquarters in a model of diabetes induced by streptozotocin .⁵

1.Lawrence, C.L., Proks, P., Rodrigo, G.C., et al.Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cellsDiabetologia44(8)1019-1025(2001) 2.Proks, P., Reimann, F., Green, N., et al.Sulfonylurea stimulation of insulin secretionDiabetes51(3)S368-S376(2002) 3.Shimoyama, T., Yamaguchi, S., Takahashi, K., et al.Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocationMetabolism55(6)722-730(2006) 4.Mamputu, J.C., and Renier, G.Gliclazide decreases vascular smooth muscle cell dysfuntion induced by cell-meditated oxidized low-density lipoproteinMetabolism50(6)688-695(2001) 5.Pulido, N., Suarez, A., Casanova, B., et al.Gliclazide treatment of streptozotocin diabetic rats restores GLUT4 protein content and basal glucose uptake in skeletal muscleMetabolism46(12 Suppl 1)10-13(1997)