Abstract
| Language | English |
|---|---|
| Pages | 327-333 |
| Journal | European Journal of Pharmacology |
| Volume | 408 |
| Issue number | 3 |
| Publication status | Published - Nov 2000 |
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Desensitization of sulphonylurea- and nutrient-induced insulin secretion following prolonged treatment with glibenclamide. / Ball, AJ; Flatt, Peter; McClenaghan, Neville.
In: European Journal of Pharmacology, Vol. 408, No. 3, 11.2000, p. 327-333.Research output: Contribution to journal › Article
TY - JOUR
T1 - Desensitization of sulphonylurea- and nutrient-induced insulin secretion following prolonged treatment with glibenclamide
AU - Ball, AJ
AU - Flatt, Peter
AU - McClenaghan, Neville
PY - 2000/11
Y1 - 2000/11
N2 - Functional effects of prolonged exposure to the sulphonylurea glibenclamide were examined in a popular clonal pancreatic p-cell line, denoted as BRIN-BD11. In acute 20-min incubations, 200 muM of tolbutamide or glibenclamide stimulated insulin release from non-depolarized and depolarized cells, which was dramatically reduced following 18-h culture with 100 muM glibenclamide. Sulphonylurea desensitization in non-depolarized cells was reversed following 6-36-h subsequent culture in the absence of glibenclamide. However, desensitization of insulinotropic effects of sulphonylureas in depolarized cells following glibenclamide culture and associated decline in cellular insulin content was not fully reversible. Culture with 100 muM glibenclamide also markedly reduced the acute insulinotropic actions of glucose, L-alanine, L-arginine, 2-ketoisocaproic acid (KIC) and KCl. These effects were almost completely reversed following 18-h culture in the absence of the sulphonylurea. (C) 2000 Elsevier Science B.V. All rights reserved.
AB - Functional effects of prolonged exposure to the sulphonylurea glibenclamide were examined in a popular clonal pancreatic p-cell line, denoted as BRIN-BD11. In acute 20-min incubations, 200 muM of tolbutamide or glibenclamide stimulated insulin release from non-depolarized and depolarized cells, which was dramatically reduced following 18-h culture with 100 muM glibenclamide. Sulphonylurea desensitization in non-depolarized cells was reversed following 6-36-h subsequent culture in the absence of glibenclamide. However, desensitization of insulinotropic effects of sulphonylureas in depolarized cells following glibenclamide culture and associated decline in cellular insulin content was not fully reversible. Culture with 100 muM glibenclamide also markedly reduced the acute insulinotropic actions of glucose, L-alanine, L-arginine, 2-ketoisocaproic acid (KIC) and KCl. These effects were almost completely reversed following 18-h culture in the absence of the sulphonylurea. (C) 2000 Elsevier Science B.V. All rights reserved.
M3 - Article
VL - 408
SP - 327
EP - 333
JO - European Journal of Pharmacology
T2 - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -