Gliclazide is a blocker of pancreatic β-cell ATP-sensitive potassium channels with IC50 of 184 nM in murine. It belongs to the sulfonylurea class of insulin secretagoguesIt. Gliclazide is an antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM).
Potassium (K) channel, or the ATP-sensitive potassium channel, is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The potassium channel plays a major role in controlling the beta-cell membrane potential and thereby insulin release.
Gliclazide is an ATP-sensitive potassium channel blocker. In an experimental system, potassium channel activities of cloned beta-cells were measured by recording macroscopic currents in giant inside-out membrane patches. The results showed that gliclazide inhibited beta-cell K (ATP) channels at two sites: a high-affinity site, which is half-maximally blocked (Ki) at 50 nM and a low-affinity site with a Ki of 3 mM. In the other hand, cloned cardiac and smooth muscle K(ATP) channels did not show high-affinity block by gliclazide[3]. According to another report, Gliclazide blocked whole-cell beta-cell KATP currents with an IC50 of 184 nM but was much less effective in cardiac and smooth muscle, with IC50s of 19.5 μM and 37.9 μM, respectively[4]. In an experiment assessing the protective effect of gliclazide on 3T3L1 adipocytes from insulin resistance induced by oxidative stress, it was found that addition of 0.1 to 10 μM gliclazide to hydrogen peroxide-treated cells dose-dependently restored glucose uptake, with 5 μM gliclazide significantly restoring glucose uptake to 93.3 ± 6.6% even under hydrogen peroxide, while the data of the corresponding control group was 65.9 ± 7.8%[5].
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