Objective To test if gliquidone (gli) induces β cells
desensitization as other sulfonylurea (Su) and the features of the
reversion of responsiveness. Methods An obese type 2 diabetic (DM2) rat model was developed, for which low dose streptozocin (STZ,25 mg/L) was injected ip. into Wistar rats followed by high sucrose-fat diet feeding for 8 weeks as described previously. Islet cells from normal and DM2 rats were isolated and cultured over 24 h in a medium with or without gli and the static Ins secretion at various time intervals were measured by RIA. These islet cells either untreated or pre-treated for 24 h with various dosages of gli (500;1000;1500 ng/ml) were perifused by a column perifusion system. Ins release in
response to the corresponding doses of gli was evaluated. Results Insulin secretion decreased remarkably under the static stimuli to DM2 islets, compared with that of the normal controls (P<0.05). Insulin secretion in normal islets in response to 500 and 1000 ng/ml gli rose to a peak level at the second hour, and then declined with the time, but the islets did not respond to 1500 ng/ml gli. Gli pre-treated islets gave no response to acute gli stimuli. Short term (10 min) removal of the islets from gli-exposure could not reverse the responsiveness; however, after the exposure to gli being discontinued for 20 h,
desensitization could be reverted completely in use of 500 ng/ml gli; partially in use of 1000 ng/ml gli; but not in use of 1500 ng/ml gli. Conclusion The results indicated that the exposure of β cell to gli at various concentrations induced selective desensitization of the β cell to gli stimuli; and the desensitization could be reverted completely or partially after the exposure being discontinued for 20 h to 500 ng/ml and 1000 ng/ml but not to 1500 ng/ml gli, respectively. The restoration of the response of β cell to gli stimuli was dose-dependent and time-dependent.