Free Insulin-Like Growth Factor I (IGF-I) and IGF-II in Human Saliva*

Abstract

We found that human saliva contains both insulin-like growth factor I (IGF-I) and IGF-II but no significant binding proteins, and that salivary IGF-I levels correlated with plasma GH levels. Mixed saliva had globular proteins precipitated by freezing/thawing. After centrifugation the clear supernatant was used directly in the IGF-I RIA (Van Wyk and Underwood antibody) and in a human placental membrane RRA for IGF-II. The lower limits of detection for IGF-I and IGF-II were 0.7 ng/mL (micrograms/L) and 1.2 ng/mL (micrograms/L), respectively. Iodinated IGF added to saliva was not degraded, as assessed by trichloroacetic acid precipitability and placental membrane binding. In saliva from 14 normal subjects, IGF-I was measurable in all. IGF-II was detectable only in 8 of 14 subjects; the mean value in these 8 subjects was 2.6 +/- 0.6 (+/- SE) ng/mL (micrograms/L). The mol wt of salivary IGF was similar to that of free plasma IGF after acid or neutral pH gel chromatography. Human saliva contained no significant IGF-binding protein. Eluates from neutral gel chromatography of concentrated (20-fold) normal saliva did not inhibit IGF-II binding to placental membrane receptors. Eluted proteins from saliva samples subjected to prior acid gel chromatography failed to bind radiolabeled IGF after neutralization. Saliva samples assayed for binding protein using an amniotic fluid binding protein RIA had values at or below the lower limit of detection [less than 0.06 micrograms eq/mL (mgeq/L)]. Salivary IGF-I concentrations did not change with increasing salivary flow rates above normal, with time of day, or with storage at room temperature for up to 24 h before freezing. The mean IGF-I concentration in mixed saliva from 14 normal young adults (8 men) was 2.3 +/- 0.3 (+/- SE) ng/mL (micrograms/L), and their mean plasma IGF-I level was 315 +/- 27 ng/mL (micrograms/L). Mean salivary IGF-I was significantly lower in 15 patients with GH deficiency [1.3 +/- 0.2 ng/mL (micrograms/L); P less than 0.01] and 8-fold higher in 5 acromegalic patients [17.2 +/- 6.3 ng/mL (micrograms/L); P less 0.01]. Removal of their GH adenomas led to a fall in salivary IGF-I to 5.6 +/- 1.3 ng/mL (micrograms/L); P less than 0.05). In summary, saliva contains free IGFs but no significant quantities of specific binding proteins. Salivary IGF-I levels reflect the GH status of the donor.

Free insulin‐like growth factors (IGF‐I and IGF‐II) in human serum

“…The fraction of free IGFs has never unequivocally been demonstrated, but most studies find that the percentage of free IGF-I in healthy subjects accounts for l-5% of total, extractable IGF-I [8,12,24]. Our results are considerably lower, being 0.38 + 0.02% (range 0.14-& 76%).…”

Wound Healing and Expression of Antimicrobial Peptides/Polypeptides in Human Keratinocytes, a Consequence of Common Growth Factors

“…Furthermore, these growth factors had a synergistic/additive effect in inducing expression of some of these antimicrobial peptides/polypeptides. These growth factors are present in saliva (31,32) and have long been thought to support the proliferation of cells in wounds when animals lick their wounds. Our findings indicate that these growth factors may also aid in the prevention of infections in the wound.…”

Role of Hepatocyte Growth Factor and c-Met Receptor in Neoplastic Conditions of Salivary Glands

“…Human saliva contains cell growth factors such as insulin-like growth factors I and II [12], transforming growth factor-alpha [21], vascular endothelial growth factor [36], EGF [24] and fibroblast growth factor-2 [16]. These growth factors have been assumed to play roles in wound healing of the upper digestive tract.…”