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].
Gliclazide/格列齐特 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary β-cells
20 nM
12 h
Gliclazide decreased C3 levels and inhibited islet β-cell dedifferentiation.
iScience. 2024 Sep 28;27(10):111064.
MIN-6 cells
20 nM
12 h
Gliclazide decreased C3 levels and inhibited islet β-cell dedifferentiation.
iScience. 2024 Sep 28;27(10):111064.
Gliclazide/格列齐特 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Type 2 diabetes model
Oral
6 mg/kg
Once daily for one month
Evaluate the effect of gliclazide on islet β-cell dedifferentiation in T2DM mice, results showed that gliclazide decreased C3 levels and inhibited β-cell dedifferentiation.
iScience. 2024 Sep 28;27(10):111064.
Male Wistar rats
Type 1 diabetes model
Intra-arterial injection
20mg/kg
Single dose, samples taken after 240 seconds
To investigate the effect of deoxycholic acid on the permeation of gliclazide through the blood-brain barrier. Results showed increased penetration of gliclazide in diabetic animals, and DA pretreatment further enhanced penetration in both healthy and diabetic animals.
J Diabetes Res. 2013;2013:598603
Male Golden Syrian hamsters
5-FU-induced oral mucositis model
Oral gavage
1, 5, or 10 mg/kg
Once daily for 10 days
To evaluate the effect of gliclazide on 5-FU-induced oral mucositis. Results showed that gliclazide at 10 mg/kg significantly reduced oxidative stress and inflammation, and accelerated mucosal recovery.
搜索
