Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency

Claus B. Juhl, Niels PØrksen, Malene Hollingdal, Jeppe Sturis, Steven Pincus, Johannes D. Veldhuis, Anders Dejgaard, Ole Schmitz

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25 Scopus citations

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. RESEARCH DESIGN AND 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 · 1-1 · pulse - 1, P = 0.02) and amplitude (6.1 ± 0.9 vs. 7.7 ± 1.2 pmol · 1-1 · 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 · l-1 · 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.

Original languageEnglish (US)
Pages (from-to)675-681
Number of pages7
JournalDiabetes care
Volume23
Issue number5
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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    Juhl, C. B., PØrksen, N., Hollingdal, M., Sturis, J., Pincus, S., Veldhuis, J. D., Dejgaard, A., & Schmitz, O. (2000). Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency. Diabetes care, 23(5), 675-681. https://doi.org/10.2337/diacare.23.5.675