Repaglinide treatment amplifies first-phase insulin secretion and high-frequency pulsatile insulin release in Type 2 diabetes

M. Hollingdal, J. Sturis, M. A. Gall, P. Damsbo, S. Pincus, J. D. Veldhuis, N. Pørksen, O. Schmitz, Claus B. Juhl

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Aims/hypothesis: First-phase insulin release and coordinated insulin pulsatility are disturbed in Type 2 diabetes. The present study was undertaken to explore a possible influence of the oral prandial glucose regulator, repaglinide, on first-phase insulin secretion and high-frequency insulin pulsatility in Type 2 diabetes. Methods: We examined 10 patients with Type 2 diabetes in a double-blind placebo-controlled, cross-over design. The participants were treated for 6 weeks with either repaglinide [2-9 mg/day (average 5.9 mg)] or placebo in random order. At the end of each treatment period, first-phase insulin secretion was measured. Entrainment of insulin secretion was assessed utilizing 1-min glucose bolus exposure (6 mg/kg body weight every 10 min) for 60 min during (A) baseline conditions, i.e. 12 h after the last repaglinide/placebo administration, and (B) 30 min after an oral dose of 0.5 mg repaglinide/placebo with subsequent application of time-series analyses. Results: Postprandial (2-h) blood glucose was significantly reduced by repaglinide after 5 weeks of treatment (P < 0.001). The fall in HbA lc did not reach statistical significance (P = 0.07). AUC ins,0-12min during the first-phase insulin secretion test was enhanced (P < 0.05). In addition, glucose entrained insulin secretory burst mass and amplitude increased markedly (burst mass: repaglinide, 44.4 ± 6.0 pmol/l/pulse vs. placebo, 31.4 ± 3.3 pmol/l/pulse, P < 0.05; burst amplitude: repaglinide, 17.7 ± 2.4 pmol/l/min vs. placebo, 12.6 ± 1.3 pmol/l/min, P < 0.05) while basal insulin (non-pulsatile) secretion was unaltered. After acute repaglinide exposure (0.5 mg) basal insulin secretion increased significantly (P < 0.05). Neither acute nor chronic repaglinide administration influenced frequency or regularity of insulin pulses during entrainment. Conclusion/interpretation: Repaglinide augments first-phase insulin secretion as well as high-frequency insulin secretory burst mass and amplitude during glucose entrainment in patients with Type 2 diabetes, while regularity of the insulin release process was unaltered.

Original languageEnglish (US)
Pages (from-to)1408-1413
Number of pages6
JournalDiabetic Medicine
Volume22
Issue number10
DOIs
StatePublished - Oct 1 2005

Keywords

  • Deconvolution analysis
  • First-phase insulin secretion
  • Pulsatile insulin secretion
  • Repaglinide

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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