Desensitization of sulphonylurea- and nutrient-induced insulin secretion following prolonged treatment with glibenclamide

AJ Ball, Peter Flatt, Neville McClenaghan

Research output: Contribution to journal › Article

20 Citations (Scopus)

Abstract

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.
LanguageEnglish
Pages327-333
JournalEuropean Journal of Pharmacology
Volume408
Issue number3
Publication statusPublished - Nov 2000

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Glyburide
Insulin
Food
Tolbutamide
Alanine
Arginine
Glucose
Cell Line
Acids

Cite this

Ball, AJ ; Flatt, Peter ; McClenaghan, Neville. / Desensitization of sulphonylurea- and nutrient-induced insulin secretion following prolonged treatment with glibenclamide. In: European Journal of Pharmacology. 2000 ; Vol. 408, No. 3. pp. 327-333.
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Ball, AJ, Flatt, P & McClenaghan, N 2000, 'Desensitization of sulphonylurea- and nutrient-induced insulin secretion following prolonged treatment with glibenclamide', European Journal of Pharmacology, vol. 408, no. 3, pp. 327-333.

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

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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.

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Ball AJ, Flatt P, McClenaghan N. Desensitization of sulphonylurea- and nutrient-induced insulin secretion following prolonged treatment with glibenclamide. European Journal of Pharmacology. 2000 Nov;408(3):327-333.