IGF-I inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-I infusion rates

Niels Pørksen, Mehboob A. Hussain, T. L. Bianda, Birgit Nyholm, Jens S. Christiansen, Peter C. Butler, Johannes D. Veldhuis, E. Rudi Froesch, Ole Schmitz

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Insulin-like growth factor I (IGF-I) shares structural and functional features with insulin, affects carbohydrate metabolism, and inhibits insulin secretion. Insulin secretion is pulsatile, and it is regulated by changing frequency and/or mass of secretory bursts. To examine the mechanism of IGF- I's inhibition of insulin secretion, eight healthy volunteers were studied three times. During glucose infusion (2.5 mg · kg-1 · min-1) blood was sampled minutely at time 75-200 rain for triplicate insulin concentration measurements by enzyme-linked immunosorbent assay (ELISA; coefficient of variation 2.1%). Time 125 min infusion of saline, low-dose IGF-I (0.025 μg · kg-1 · min-1) or high-dose IGF-I (0.15 μg · kg-1 · min-1) was commenced and continued until 200 min. Data were compared before (75-125 min) vs. during infusion (150-200 min). Insulin concentration time series were deconvolved, using validated pulse-detection criteria, to assess insulin secretory burst mass and frequency. During saline infusion no time effect occurred. After IGF-I infusion, serum C-peptide decreased (582 ± 85 vs. 481 ± 82 pM, low-dose IGF-I, P < 0.05; 539 ± 84 vs. 427 ± 69 pM, high-dose IGF-I, P < 0.01). Total insulin secretion rates decreased by 17 and 21%, respectively, via specific inhibition of the insulin secretory burst mass (31 ± 8 vs. 20 ± 4 pmol/ml, low-dose IGF-I, P = 0.06; 22 ± 4 vs. 17 ± 3 pmol/ml, high-dose IGF-I, P < 0.05), whereas the frequency was not affected (10.5 ± 1.3 vs. 10.7 ± 1.3 pulses/h, low-dose IGF-I, P = 0.85; 8.7 ± 1.0 vs. 11.1 ± 1.2 min/pulse, high-dose IGF-I, P = 0.15). We conclude that IGF- I inhibits pulsatile insulin secretion by specific inhibition of mass but not frequency of secretory bursts.

Original languageEnglish (US)
Pages (from-to)E352-E358
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume272
Issue number3 35-3
DOIs
StatePublished - Mar 1997

Keywords

  • C-peptide
  • amplitude
  • dose response
  • pulsatility
  • somatostatin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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    Pørksen, N., Hussain, M. A., Bianda, T. L., Nyholm, B., Christiansen, J. S., Butler, P. C., Veldhuis, J. D., Froesch, E. R., & Schmitz, O. (1997). IGF-I inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-I infusion rates. American Journal of Physiology - Endocrinology and Metabolism, 272(3 35-3), E352-E358. https://doi.org/10.1152/ajpendo.1997.272.3.e352