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

被引:30
作者
Porksen, N
Hussain, MA
Bianda, TL
Nyholm, B
Christiansen, JS
Butler, PC
Veldhuis, JD
Froesch, ER
Schmitz, O
机构
[1] UNIV ZURICH HOSP, DEPT ENDOCRINOL & METAB, CH-8091 ZURICH, SWITZERLAND
[2] MAYO CLIN, ENDOCRINE RES UNIT, ROCHESTER, MN 55905 USA
[3] UNIV VIRGINIA, DEPT MED, CHARLOTTESVILLE, VA 22908 USA
[4] NATL SCI FDN CTR BIOL TIMING, CHARLOTTESVILLE, VA 22908 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1997年 / 272卷 / 03期
关键词
pulsatility; somatostatin; C-peptide; dose response; amplitude;
D O I
10.1152/ajpendo.1997.272.3.E352
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 min 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 mu g . kg(-1). min(-1)) or high-dose IGF-I (0.15 mu g . 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.
引用
收藏
页码:E352 / E358
页数:7
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