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

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, whic h was dramatically reduced following 18-h culture with 100 muM glibenclamid e. Sulphonylurea desensitization in non-depolarized cells was reversed foll owing 6-36-h subsequent culture in the absence of glibenclamide. However, d esensitization of insulinotropic effects of sulphonylureas in depolarized c ells following glibenclamide culture and associated decline in cellular ins ulin content was not fully reversible. Culture with 100 muM glibenclamide a lso markedly reduced the acute insulinotropic actions of glucose, L-alanine , L-arginine, 2-ketoisocaproic acid (KIC) and KCl. These effects were almos t completely reversed following 18-h culture in the absence of the sulphony lurea. (C) 2000 Elsevier Science B.V. All rights reserved.