| Description: |
Gliclazide is a whole-cell beta-cell ATP-sensitive potassium currents blocker with an IC50 of 184 nM.Target: Potassium Channelgliclazide further characterize its mechanism of hypoglycemic effect: the observed improvements in insulin sensitivity and in GLUT4 translocation indicate that gliclazide counters the hydrogen peroxide-induced insulin resistance in 3T3L1 adipocytes and also would further augment the hypoglycemic effect of this drug as insulinotropic sulfonylurea [1]. Gliclazide blocked whole-cell beta-cell KATP currents with an IC50 of 184 +/- 30 nmol/l (n = 6-10) but was much less effective in cardiac and smooth muscle (IC50s of 19.5 +/- 5.4 micromol/l (n = 6-12) and 37.9 +/- 1.0 micromol/l (n = 5-10), respectively). In all three tissues, the action of the drug on whole-cell KATP currents was rapidly reversible. In inside-out patches on beta-cells, gliclazide (1 micromol/l) produced a maximum of 66 +/- 13 % inhibition (n = 5), compared with more than 98 % block in the whole-cell configuration. Gliclazide is a high-potency sulphonylurea which shows specificity for the pancreatic beta-cell KATP channel over heart and smooth muscle. In this respect, it differs from glibenclamide [2]. |
| References: |
[1]. Shimoyama, T., et al., Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocation. Metabolism, 2006. 55(6): p. 722-30.
[2]. Lawrence, C.L., et al., Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. Diabetologia, 2001. 44(8): p. 1019-25. |
