Objective: To test if gliquidone (gli) induces beta 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 i.p. 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 beta cell to gli at various concentrations induced selective desensitization of the beta 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 beta cell to gli stimuli was dose-dependent and time-dependent.