Orcadian Variation of Gh‐independent Igf‐binding Protein in Diabetes Mellitus and Its Relationship to Insulin. A New Role for Insulin?

Abstract

Evidence is accumulating that a non-GH dependent insulin-like growth factor-binding protein (IGF-BP) is not only a carrier protein but also has an active role in the growth process. We have measured levels of this IGF-BP, using a specific RIA, over 12 or 24-h periods in 11 adolescents with diabetes mellitus and five normal adults. In each of the normal the IGF-BP was undetectable for most of the day but with a broad nocturnal peak observed, with levels up to 50 micrograms/l. The levels of IGF-BP were unrelated to the secretory pattern for GH but correlated inversely with the concentration of circulating insulin. In the diabetics a very similar pattern was observed, but with detectable levels throughout the day and much higher peak levels seen at night. Peak levels were up to 120 micrograms/l if a long-acting insulin preparation was administered in the evening but were 400-500 micrograms/l if the long-acting preparation was administered in the morning. The IGF-BP was strongly correlated with plasma glucose in this latter group. In a further group of diabetics overnight profiles were obtained on two separate nights, a normal night and a night with euglycaemia maintained with a glucose clamp technique. Euglycaemia failed to affect peak levels of the binding protein, although the shape of the nocturnal peak was altered consistent with the altered pattern of circulating free insulin. In this group a strong inverse correlation was obtained between the IGF-BP and free insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional modulation of canine insulin-like growth factors and their binding proteins

“…Canine serum IGF-I and -II concentrations were measured in heterologous RIA, with procedures modified from those described by Blum et al (1988), Holly et al (1988), and Morrell et al (1989), using monoclonal antibodies to human IGF-I (Blood Products Ltd, Elstree, Herts, UK) and rat IGF-II (Upstate Biotechnology Incorporated, Lake Placid, NY, USA). Serum samples underwent formic acid-acetone extraction (Bowsher et al 1991) before assay to separate IGFs from their binding proteins.…”

Clinical implications of hyperinsulinaemia in women

“…Fasting serum insulin is negatively associated with IGFBP-1 concentrations in women with PCOS (Suikkari et al, 1989;Pekonen et at., 1989) and with normal ovaries . It has been proposed that circulating IGFBP-I reduces IGF-I bioavailability (Holly et al, 1989), thus suppression of IGFBP-1 by insulin may increase IGF-I action (Conover & Lee, 1990;Holly et al, 1988;Rutanen et al, 1988). In addition, IGFBP-1 has been found in follicular fluid (in proportion to serum concentrations) raising the possibility of an intra-ovarian role for this binding protein in the regulation of IGF-I .…”

Microencapsulated octreotide pamoate in advanced gastrointestinal and pancreatic cancer: a phase I study

“…IGFBP-3 (Cwyfan-Hughes et al, 1993) and IGFBP-1 (Holly et al, 1988) and octreotide (del Pozo et al, 1986) were directly measured using RIA. Plasma insulin and C-peptide were measured using RIA kits purchased from Diagnostic Products Corporation (Los Angeles, CA, USA).…”

“…Plasma levels of IGF-I (Holly et al, 1988) and IGF-lI (Davies et al, 1991) were measured using RIA after acid-acetone extraction. IGFBP-3 (Cwyfan-Hughes et al, 1993) and IGFBP-1 (Holly et al, 1988) and octreotide (del Pozo et al, 1986) were directly measured using RIA.…”