IGF-I inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-I infusion rates.
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 x kg(-1) x 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 microg x kg(-1) x min(-1)) or high-dose IGF-I (0.15 microg x kg(-1) x 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.
Pørksen
N
N
Department of Endocrinology and Metabolism M, Aarhus University Hospital, Denmark.
Hussain
M A
MA
Bianda
T L
TL
Nyholm
B
B
Christiansen
J S
JS
Butler
P C
PC
Veldhuis
J D
JD
Froesch
E R
ER
Schmitz
O
O
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D012636:Secretory Rate / Q000187:drug effects
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D007334:Insulin-Like Growth Factor I