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

Eur J Pharmacol. 2000 Nov 24;408(3):327-33. doi: 10.1016/s0014-2999(00)00782-2.


Functional effects of prolonged exposure to the sulphonylurea glibenclamide were examined in a popular clonal pancreatic beta-cell line, denoted as BRIN-BD11. In acute 20-min incubations, 200 microM of tolbutamide or glibenclamide stimulated insulin release from non-depolarized and depolarized cells, which was dramatically reduced following 18-h culture with 100 microM 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 microM 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / physiology
  • Alanine / pharmacology
  • Animals
  • Arginine / pharmacology
  • Cell Line
  • Culture Media / pharmacology*
  • Dose-Response Relationship, Drug
  • Glucose / pharmacology
  • Glyburide / pharmacology*
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Keto Acids / pharmacology
  • Potassium Channels / physiology
  • Potassium Chloride / pharmacology
  • Sulfonylurea Compounds / pharmacology*
  • Tolbutamide / pharmacology


  • Culture Media
  • Insulin
  • Keto Acids
  • Potassium Channels
  • Sulfonylurea Compounds
  • Potassium Chloride
  • alpha-ketoisocaproic acid
  • Adenosine Triphosphate
  • Arginine
  • Tolbutamide
  • Glucose
  • Alanine
  • Glyburide