Therapeutical concentrations of tolbutamide, glibenclamide, gliclazide and gliquidone at different glucose levels: in vitro effects on pancreatic A- and B-cell function

Diabetes Res Clin Pract. 1992 Dec;18(3):197-206. doi: 10.1016/0168-8227(92)90146-i.

Abstract

In the classical model of isolated perfused rat pancreas four commonly used sulfonylureas--tolbutamide, glibenclamide, gliquidone and gliclazide--were investigated at therapeutical concentrations at three different glucose levels (with 0, 2.22 and 5 mmol/l glucose surrounding) and in the presence of a metabolic stimulus with glucose at 8.33 mmol/l. All the sulfonylureas stimulated the B-cell function. Tolbutamide, gliquidone and gliclazide produced a prompt biphasic hormone release while glibenclamide induced a delayed monophasic insulin secretion. In all cases the amount of insulin released depended on the metabolic condition. As the environmental glucose levels fell, the sulfonylureas' stimulatory effect on the B-cell function decreased. At the therapeutical concentrations we tested, no sulfonylurea influenced A-cell activity whether directly or indirectly via an insulin-mediated paracrine inhibition of glucagon release.

MeSH terms

  • Animals
  • Blood Glucose / physiology
  • Dose-Response Relationship, Drug
  • Gliclazide / pharmacology*
  • Glucagon / metabolism*
  • Glucose / pharmacology*
  • Glyburide / pharmacology*
  • Hypoglycemic Agents / pharmacology*
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Kinetics
  • Male
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonylurea Compounds / pharmacology*
  • Time Factors
  • Tolbutamide / pharmacology*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Glucagon
  • Tolbutamide
  • gliquidone
  • Gliclazide
  • Glucose
  • Glyburide