[Gliquidon induced-desensitization of pancreatic beta cells and the partial reversion of responsiveness after the desensitization of exposure to drug in normal and STZ type 2 diabetic rats].
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.


CONCLUSIONS
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.
Wang
Shuang
S
Department of Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
Li
Xiu-jun
XJ
Yang
Hai-yan
HY
Zhao
Gui-zhi
GZ
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013997:Time Factors
D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C010969:gliquidone