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

  1. M. Hollingdal1,
  2. J. Sturis1,2,
  3. M.-A. Gall1,2,
  4. P. Damsbo1,2,
  5. S. Pincus1,3,
  6. J. D. Veldhuis1,4,
  7. N. Pørksen1,
  8. O. Schmitz1,
  9. C. B. Juhl1,*

Article first published online: 9 JUN 2005

DOI: 10.1111/j.1464-5491.2005.01652.x

Issue

Diabetic Medicine

Diabetic Medicine

Volume 22, Issue 10, pages 1408–1413, October 2005

Additional Information

How to Cite

Hollingdal, M., Sturis, J., Gall, M.-A., Damsbo, P., Pincus, S., Veldhuis, J. D., Pørksen, N., Schmitz, O. and Juhl, C. B. (2005), Repaglinide treatment amplifies first-phase insulin secretion and high-frequency pulsatile insulin release in Type 2 diabetes. Diabetic Medicine, 22: 1408–1413. doi: 10.1111/j.1464-5491.2005.01652.x

Author Information

  1. 1

    Department of Endocrinology and Diabetes, Århus Sygehus and Department of Clinical Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark,

  2. 2

    Novo Nordisk, Bagsvaerd, Denmark,

  3. 3

    Guilford, CT, USA,

  4. 4

    Division of Endocrinology, Mayo Clinic, Rochester, MN, USA

*Claus B. Juhl MD PhD, Department of Medicine M (Endocrinology and Diabetes), Aarhus Sygehus, Noerrebrogade 44, 8000 Aarhus C, Denmark. E-mail: claus.juhl@dadlnet.dk

Publication History

  1. Issue published online: 13 SEP 2005
  2. Article first published online: 9 JUN 2005
  3. Accepted 19 December 2004

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Keywords:

  • deconvolution analysis;
  • first-phase insulin secretion;
  • pulsatile insulin secretion;
  • repaglinide

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 HbA1c did not reach statistical significance (P = 0.07). AUCins,0−12 min 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.

Diabet. Med. (2005)

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