title: Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency.
abstract: OBJECTIVE
  Repaglinide is a new oral hypoglycemic agent that acts as a prandial glucose regulator proposed for the treatment of type 2 diabetes by stimulating insulin secretion. The aim of this study was to explore actions of repaglinide on the rapid pulsatile insulin release by high-frequency insulin sampling and analysis of insulin-concentration time series.
  
  
  METHODS
  We examined 8 healthy lean male subjects in a single-dose double-blind placebo-controlled crossover design. After the subjects underwent an overnight fast, blood sampling was initiated and continued every minute for 120 min. After 40 min, a single dose (0.5 mg) of repaglinide or placebo was given. Serum insulin-concentration time series were assessed by deconvolution analyses and the regularity statistic by approximate entropy (ApEn).
  
  
  RESULTS
  Average insulin concentration was increased after repaglinide administration (basal vs. stimulated period, P values are placebo vs. repaglinide) (25.1 +/- 3.6 vs. 33.5 +/- 4.1 pmol/l, P < 0.001). Insulin secretory burst mass (15.8 +/- 2.2 vs. 19.6 +/- 2.8 pmol x l(-1) x pulse(-1), P = 0.02) and amplitude (6.1 +/- 0.9 vs. 7.7 +/- 1.2 pmol x l(-1) x min(-1), P = 0.008) were augmented after repaglinide administration. A concomitant trend toward an increase in basal insulin secretion was observed (2.5 +/- 0.3 vs. 3.2 +/- 0.4 pmol x l(-1) x min(-1), p = 0.06), while the interpulse interval was unaltered (6.8 +/- 1.0 vs. 5.4 +/- 0.4 min/pulse, P = 0.38). ApEn increased significantly after repaglinide administration (0.623 +/- 0.045 vs. 0.670 +/- 0.034, P = 0.04), suggesting less orderly oscillatory patterns of insulin release.
  
  
  CONCLUSIONS
  In conclusion, a single dose of repaglinide amplifies insulin secretory burst mass (and basal secretion) with no change in burst frequency. The possible importance of these mechanisms in the treatment of type 2 diabetes characterized by disrupted pulsatile insulin secretion remains to be clarified.
authors.affiliation: Department of Medicine M (Endocrinology & Diabetes), Arhus Kommunehospital, University Hospital of Arhus, Denmark. cbj@dadlnet.dk
authors.forename: C B
authors.initials: CB
authors.lastname: Juhl
authors.forename: N
authors.initials: N
authors.lastname: Pørksen
authors.forename: M
authors.initials: M
authors.lastname: Hollingdal
authors.forename: J
authors.initials: J
authors.lastname: Sturis
authors.forename: S
authors.initials: S
authors.lastname: Pincus
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: A
authors.initials: A
authors.lastname: Dejgaard
authors.forename: O
authors.initials: O
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002219:Carbamates / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D010919:Placebos
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D010919:Placebos; C072379:repaglinide