REGULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 DURING THE24-HOUR METABOLIC CLOCK AND IN RESPONSE TO HYPOINSULINEMIA INDUCED BYFASTING AND SANDOSTATIN IN NORMAL WOMEN

OBJECTIVE: To establish the relation of insulin-like growth factor-I ( IGF-I) and IGF-binding protein-1 (IGFBP-1) with 24-hour metabolic excu rsions in normal healthy women and in response to acute interruption o f metabolic homeostasis by hypoinsulinemia. METHODS: Hourly blood samp les during the 24-hour metabolic clock were obtained from seven normal ly cycling women. Uniform dietary composition (50% carbohydrate, 35% f at, and 15% protein) and timing of meals (8 AM, 12 PM, and 6 PM) were prescribed. Daytime hypoinsulinemia was induced by omitting meals and by Sandostatin (100 mu g) administration. Changes in serum levels of g lucose, insulin, cortisol, IGF-I, and IGFBP-1 were measured. RESULTS: The diurnal pattern of serum IGFBP-1 levels during the 24-hour metabol ic clock was characterized by a rapid fall during the feeding phase of the day and a progressive 3.5-fold rise during nocturnal fasting; IGF -I levels were unchanged. Changes in IGFBP-1 levels were in parallel t o those of cortisol and were inversely related to increases in glucose (80%) and insulin (tenfold) levels after each meal and to their decli ne during nocturnal fasting. Daytime fasting and administration of San dostatin were accompanied by rapid and sustained increases in IGFBP-1 when insulin levels declined to 54 +/- 20 pmol/L. CONCLUSIONS: With co nstant levels of IGF-I, the diurnal rhythm of IGFBP-1 may subserve a p hysiologic function by coordinating insulin and IGF-I action with subs trate availability. Fluctuations of insulin levels during the 24-hour metabolic clock in normal women appear to serve as a signal, with an i nhibitory effect on IGFBP-1 production when levels are above 70 pmol/L and a stimulatory effect at levels below 70 pmol/L. These findings pr ovide a basis for future investigations in women with nutritionally re lated reproductive disorders.