化合物信息

S2601  

Research Area: Metabolic Disease
Biological Activity:
Gliclazide (Diamicron) is a whole-cell beta-cell ATP-sensitive potassium currents blocker with an IC50 of 184 ± 30 nM. Gliclazide (Diamicron) binds to sulfonylurea receptors on the surface of the Beta islet cells found in the pancreas. This binding effectively closes the K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca2+ ion channels to open increasing the Ca2+ influx. The calcium can then bind to and activate calmodulin which in turn leads to exocystosis of insulin vesicles leading to insulin release. Gliclazide is used for control of hyperglycemia in gliclazide-responsive diabetes mellitus of stable, mild, non-ketosis prone, maturity-onset or adult type. Gliclazide (Diamicron) is used when diabetes cannot be controlled by proper dietary management and exercise or when insulin therapy is not appropriate. [1][2][3]References on Gliclazide (Diamicron)[1] Diabetologia. , 2001 Aug, 44(8):1019-25[2] http://en.wikipedia.org/wiki/Gliclazide, , [3] Diabetes., 2009 Oct, 58(10):2419-24

DB01120 

G409875 

A sulfonylurea hypoglycemic agent. Used as an antidiabetic.

G2167 

Application
Used in the treatment of non-insulin dependent diabetes mellitus (NIDDM).
Biochem/physiol Actions
Oxidative modification of low-density lipoprotein (LDL) plays an important role in vascular dysfunction associated with diabetes mellitus. Gliclazide is a second-generation sulfonylurea with free-radical-scavenging activity. Incubation of human aortic smooth muscle cell (HASMC) with native human LDL (100 μg/mL) in the presence of increasing concentrations of gliclazide (1 to 10 μg/mL) resulted in a dose-dependent decrease in HASMC-mediated LDL oxidation. Exposure of HASMCs to gliclazide (1 to 10 μg/mL) and native LDL (100 μg/mL) also led to a dose-dependent decrease in oxidized LDL-induced human monocyte adhesion to HASMCs. In addition, incubation of HASMCs with gliclazide dramatically reduced the ability of oxidized LDL to stimulate the proliferation of these cells. Finally, treatment of HASMCs with gliclazide resulted in a marked decrease in oxidatively modified LDL-induced monocyte chemoattractant protein (MCP)-1 and human heat shock protein 70 (HSP 70) expression, both at the gene and protein levels. These results show that gliclazide, at concentrations in the therapeutic range (5 to 10 μg/mL), is effective in vitro in reducing vascular smooth muscle cell (VSMC) dysfunction induced by oxidatively modified LDL. Administration of gliclazide to type 2 diabetic patients could form part of the strategy for the prevention and management of diabetic cardiovascular diseases