Insulin-like growth factors and their binding proteins: review of functions and clinical applications.

Insulin-like Growth Factors I & II (IGFs I & II) circulate in a concentration 1000 times that of insulin. The effect of these growth factors appears to be regulated by their binding proteins. The clinical usefulness of the IGFs resides currently in the growth hormone disease states and their treatment, as well as tumour related hypoglycemia. The growth hormone dependent binding protein (mol. wt 53kD) appears to possess a role in growth disorders, whereas the growth hormone independent binding protein (mol. wt 28kD) has recently been found to exert a role in glucose homeostasis.

Metabolic regulation of the growth hormone independent insulin-like growth factor binding protein in human plasma.

This study examines the regulation of circulating GH-independent insulin-like growth factor binding protein, BP-28. Commencing at 22.00 h, BP-28 in 5 normal adults rose 11-fold to peak values of 120 +/- 12 micrograms/l, remained elevated between 01.00 and 08.00 h, then fell rapidly following a meal. If meals were omitted, BP-28 remained at peak levels throughout the day. The fasting BP-28 level was higher in women (141 +/- 22 micrograms/l, N = 5) than men (59 +/- 14 micrograms/l, N = 7), and pregnancy caused a further 2-fold elevation. Oral glucose rapidly lowered BP-28 in diabetic and nondiabetic pregnant women, nonpregnant women, and men. In a heterogeneous group of 18 subjects, insulin (0.1 U/kg iv), with or without simultaneous administration of GnRH and TRH, elicited a 3- to 4-fold rise in BP-28, commencing 60 min after the nadir of plasma glucose, and independent of the response in GH, PRL, TSH, LH or cortisol. We conclude that BP-28 levels in adults are metabolically regulated, and postulate a role for this protein in the maintenance of glucose homeostasis.