title: Dose-dependent effects of glyburide on insulin secretion and glucose uptake in humans.
abstract: OBJECTIVE
  To examine the relationship between plasma glyburide concentrations (0, 50, 100, 200, 400, and 800 nM) and the insulin response and glucose metabolism during euglycemic (4.6 +/- 0.1 mM) and hyperglycemic (11.6 +/- 0.2 mM) conditions.
  
  
  METHODS
  Nine healthy subjects participated in the study. Steady-state plasma glyburide concentrations were achieved by primed continuous intravenous infusion of glyburide.
  
  
  RESULTS
  During both euglycemia and hyperglycemia, glyburide enhanced insulin secretion and glucose disposal only to drug levels of 100-200 nM corresponding to an oral dose less than or equal to 10 mg.
  
  
  CONCLUSIONS
  The data suggest that glyburide (and probably other sulfonylureas), operates within a narrow range of plasma concentrations (50-200 nM), which can be achieved with very low doses of the drug. It remains to be shown whether the threshold of maximal effect also in clinical practice is achieved with lower sulfonylurea doses than that currently used.
authors.affiliation: Fourth Department of Medicine, Helsinki University Hospital, Finland.
authors.forename: L C
authors.initials: LC
authors.lastname: Groop
authors.forename: N
authors.initials: N
authors.lastname: Barzilai
authors.forename: K
authors.initials: K
authors.lastname: Ratheiser
authors.forename: L
authors.initials: L
authors.lastname: Luzi
authors.forename: E
authors.initials: E
authors.lastname: Wåhlin-Boll
authors.forename: A
authors.initials: A
authors.lastname: Melander
authors.forename: R A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015309:Glucose Clamp Technique; D005905:Glyburide / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005905:Glyburide