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Abstract.

IGF-I and -II share specific serum carrier proteins which elute on neutral Sephadex G-200 gel permeation chromatography at apparent molecular masses of 50 and 200 kD. The half-lives of free and carrier protein-bound ¹²⁵I-IGF-I and -II were determined after bolus injections of the tracers into two normal adults. Labelled IGF-I and -II migrated first with the 50-kD and later with the 200-kD complex. In these complexes their apparent half-lives were 20–30 min and 12–15 h, respectively. The apparent half-life of free ¹²⁵I-IGF-I and -II was 10–12 min. In a second set of experiments, recombinant human insulin-like growth factor I was infused during 6 days in two healthy adults at a dose of 20 μg · kg⁻¹ · h⁻¹ (corresponding to around 30 mg/day). Serum obtained before and during the infusion was subjected to neutral Sephadex G-200 gel permeation chromatography and fractions were pooled according to the apparent molecular masses at which the carrier protein complexes elute. IGF-I and -II in these pools were determined by RIA. Before the IGF-I infusion, 92 and 272 μg/l of IGF-I and -II were found in the 200-kD complex, 45 and 91 μg/l in the 50-kD complex, and 15 and 5 μg/l were present in the free form. Corresponding figures during the IGF-I infusion were 389 and 18 μg/l for the 200-Kd complex, 201 and 54 μg/l for the 50-kD complex, and 80 and < 1 μg/l for free IGF-I and -II. Using the half-lives of the tracer studies and the levels of the different molecular weight forms of IGF in serum, the production rates for IGF-I and -II were calculated to be 10 mg and 13 mg per day.

Abstract. IGF I was determined by a radioimmunoassay and IGF II by a radioreceptorassay in 20 Göttinger miniature (mini)-pigs and 13 domestic pigs of different weight and age. Immunoreactive IGF I serum levels of mini-pigs were similar to those of domestic pigs in corresponding age-classes (150–250 and 100–270 μg/l, respectively). No differences were detectable between receptor-reactive IGF II serum levels in mini-pigs (150–200 μg/l) and domestic pigs (110–270 μg/l) nor did the biological insulin-like activites (measured in the rat fat cell assay) differ in mini- and domestic pigs (81–100 and 71–98 mU insulin/l, respectively). IGF I and IGF II decreased drastically after hypophysectomy in one of the mini-pigs. Intravenous bolus injections of 30 μg/kg of recombinant human IGF I in 4 mini-pigs caused a similar degree of hypoglycemia (nadir of blood glucose 1.33 ± 0.61 mmol/l) as 0.15 IU insulin/kg, followed by a sharp growth hormone peak. We conclude that the marked difference between mini- and domestic pigs regarding body size is unrelated to serum levels of IGF I and II, a lack of response of tissues to IGF I or a reduced growth hormone secretory capacity in the mini-pig.

Abstract.

The short stature of mini-poodles is associated with low serum levels of IGF-I. Standard poodles are taller and have considerably higher serum levels of IGF-I. Low IGF-I serum levels may be a symptom or the cause of small stature. We, therefore, undertook a study in which serum IGF-I levels of mini-poodles were elevated over a prolonged period of time by a constant infusion of rhIGF-I and the growth rate of the mini-poodles was followed. We infused four mini-poodles from day 91 to day 221 of age with 6 mg/day of recombinant human insulin-like growth factor I (rhIGF-I). Serum levels of IGF-I rose from about 160 to about 500 μg/l. Blood glucose remained within normal limits. Stimulation tests with clonidine and with GHRH revealed suppression of endogenous GH secretion during the IGF-I infusion. Serum levels of IGF-II and of creatinine were lower in the IGF-I-infused animals. Radial length and body weight did not increase to a greater extent in the IGF-I infused dogs than in controls. However, 'adapted body mass index' (aBMI = gram body weight/(mm radial length)²) decreased in each of the IGF-I infused animals, whereas it increased in each of the control dogs (p <0.05). We conclude that long-term infusion of IGF-I does not stimulate growth in young minipoodles, but may change body composition.

Abstract.

Recombinant IGF-I was infused sc at a dose of 20 μg · kg⁻¹ · h⁻¹ to 2 healthy subjects during a total of 79 h. Serum levels of IGF-I rose from 93 and 177 to 502 and 616 μg/l, respectively. Fasting blood glucose remained normal. During the infusion, glomerular filtration rate increased by 31% in subject No. 1 and by 32% in subject No.2. Concomitantly, renal plasma flow increased by 26% and 22%, respectively. Proximal and distal tubular reabsorption of fluid and sodium as determined by lithium clearance was elevated to a similar extent. When determined again one week after the end of the IGF-I infusion, all parameters of renal function had returned to baseline. Sodium excretion, body weight and blood pressure did not change. We conclude that IGF-I infused at pharmacological doses has marked effects on kidney function. Future studies will be necessary to define the clinical potential of recombinant IGF-I in the treatment of diseases characterized by impaired renal perfusion and filtration.