title: Gliclazide at a lower concentration than therapeutic dose increases the sensitivity of insulin secretion to glucose in perfused rat pancreas.
abstract: We studied the difference between effects of therapeutic dose and sub-therapeutic dose of gliclazide on the glucose-induced insulin secretion.
  
  
  
  The normal rat pancreas was isolated and perfused with Krebs-Ringer buffer containing 1-14 mmol/l glucose. Influcences of 0.25 and 2.5 microg/ml gliclazide on the glucose concentration-insulin secretion curve was examined.
  
  
  
  Gliclazide at 0.25 microg/ml significantly potentiated 5-8 mmol/l glucose-induced insulin secretion (2.5 +/- 0.5 vs 1.0 +/- 0.3 mU for 15 min at 6.5 mmol/l glucose, P<0.01), but did not give influence on either 1-3 or 10-14 mmol/l glucose-induced insulin secretion. The glucose concentration, at which half-maximal insulin secretion was observed, was lower with gliclazide (5.9 mmol/l) than in the control (7.5 mmol/l). Gliclazide at 2.5 microg/ml markedly increased the maximally glucose-stimulated insulin secretion from 3.9 +/- 0.5 mU for 15 min in the control to 6.6 +/- 0.7 mU for 15 min (P<0.01). The half-maximal insulin secretion was observed at a lower glucose concentration (5.0 mmol/l) than in the absence of gliclazide.
  
  
  
  Gliclazide in sub-therapeutically low dose has different effects on insulin secretion from in therapeutic dose, namely sharpens the insulin secretion sensitivity to glucose with no influence on the maximal insulin secretion. It is possible that low doses of gliclazide might be of interest in some type 2 diabetics whose main pathophysiology is the blunting of insulin secretion response to hyperglycemia.
authors.affiliation: Third Department of Internal Medicine, Teikyo University School of Medicine, Ichihara-City 299-0111, Japan. mokuchan_14@yahoo.co.jp
authors.forename: O
authors.initials: O
authors.lastname: Mokuda
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Ooka
authors.forename: R
authors.initials: R
authors.lastname: Okazaki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005907:Gliclazide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D005907:Gliclazide; D005947:Glucose