Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia.

Abstract

A B S T R A C T Serum levels of immunoreactive insulinlike growth factors (IGF) I and II were determined by a modified IGF I and a new IGF II radioimmunoassay in normal children and adults, and in patients with acromegaly, isolated growth hormone deficiency, and extrapancreatic tumor hypoglycemia.Serum samples were gel filtered by a simple routine procedure at acidic pH to dissociate and separate IGF from the IGF carrier protein.Mean immunoreactive IGF I levels (±SD; corrected for crossreactivity of IGF II) were 193+58 ng/ml in normal adult subjects, 712+245 ng/ml in acromegalic patients and 24±14 ng/ml in patients with isolated growth hormone deficiency. The lack of growth hormone alone, irrespective of an otherwise normal hormonal status, appears to be responsible for the drastic decrease of IGF I levels.Oversecretion of growth hormone does not increase the levels of immunoreactive IGF II: mean levels (± SD; corrected for crossreactivity of IGF I) in normal and acromegalic subjects are virtually identical (647 ±126 and 641±189 ng/ml, respectively). Apparently, normal growth hormone levels stimulate IGF II production already maximally. However, in growth hormone deficiency immunoreactive IGF II is significantly decreased (252 ±99 ng/ml). Thus, IGF II, like IGF I, is growth hormone dependent. But in contrast to IGF I, the growth hormone dependence of IGF II seems to become apparent only at subnormal growth hormone levels.In normal children IGF I is age dependent: it is low in newborn cord sera (51±20 ng/ml) and gradually rises into the adult range with increasing age. At the onset of and during puberty mean IGF I levels lie above prepubertal values. In contrast, IGF II levels in normal children are independent ofage and pubertal stage beyond the first year of life, whereas newborns have significantly lower IGF II values.Hypoglycemia resulting from extrapancreatic tumors is not associated with increased immunoreactive IGF I or II levels. IGF I is decreased in most of the sera (mean level ±SD:56±39 ng/ml) whereas IGF II lies in the normal range (556±195 ng/ml).

Insulin-like growth factor I during growth in bulls

“…In humans, blood concentrations of IGF, increase . from birth up to puberty (Zapf et al, 1981) and decrease again during adult life (Clemmons and Van Wyk, 1984 (Clemmons and Van Wyk, 1984;Spencer, 1985 (Lemal et aL, 1988 (Blum et aL, 1985a (Blum et al, 1985b). The small decrease in albumin concentrations during the growth trial relative to the period of rearing was of minor concern.…”

Evaluation of the synthetic somatostatin analogue SMS 201-995 in patients with hypoglycaemia associated with hepatocellular carcinoma

“…One possibility is that the hypoglycaemia was not due to the production of an insulinomimetic peptide. Somatomedin C/IGF1 concentrations were low, and although other insulin-like growth factors were not measured, Zapf et al (1981) somatostatin analogue in inhibiting GH, rather than insulin or glucagon secretion (Bauer et al, 1982). Further studies using the native form of somatostatin might be of interest.…”

“…One possible explanation is the production by the tumour of an 'insulin-like' polypeptide (e.g., insulin-like growth factor or IGF), which has been found in the serum of such cases by some workers (Gorden et al, 1981;Daughaday et al, 1981), but not by others (Joffe et al, 1978;Zapf et al, 1981).…”

Presentation of Neuroendocrine Self in the Thymus: Toward a Novel Type of Vaccine / Immunotherapy

“…In parallel with this hierarchy, immune tolerance of IGF-2 is higher than IGF-1, and much more than insulin. This is indirectly reflected by the frequency and titer of antibodies obtained after active immunization with the three peptides [32]. In the same line of reasoning, the high occurrence of anti-insulin autoantibodies in the normal population [33] could be linked to the low level of INS expression within the human thymus.…”