Insulin-Like Growth Factor

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Serum insulin-like growth factor-I (IGF-I) levels at the higher end of the reference range have been associated with increased risk for the future development of prostate cancer. We determined whether high serum IGF-I levels are associated with precancerous lesions of the prostate. We conducted a case-control study to determine whether high serum IGF-I levels were associated with the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) among patients who presented for prostate biopsy because of an abnormal serum prostate-specific antigen level or digital rectal exam. We measured serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) prior to prostate biopsy and compared them between 103 men with HGPIN (cases) and 205 men with normal prostate histology (controls). The mean IGF-I level in patients with HGPIN (130.2 ng/mL) was significantly higher compared with controls (118.8 ng/mL, P = 0.01). The mean IGFBP-3 level in patients with HGPIN (2,393.9 ng/mL) was also higher compared with controls (2,276.0 ng/mL, P = 0.06). After adjusting for age, prostate-specific antigen, digital rectal examination, and ethnic background, the odds ratio for a HGPIN diagnosis among men in the highest relative to the lowest quartile of serum IGF-I level was 1.94 (95% confidence interval, 1.0-3.7; P = 0.04). The potential association between a high serum IGF-I level and the presence of HGPIN may represent an important clue to understanding the basis for the relationship between IGF-I physiology and prostate cancer risk. Larger studies will be required to confirm this relationship.

Nam RK, Trachtenberg J, Jewett MA, et al. Serum insulin-like growth factor-I levels and prostatic intraepithelial neoplasia: a clue to the relationship between IGF-I physiology and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2005;14(5):1270-3.

To elucidate the physiological role of insulin-like growth factor-I (IGF-I) during early pregnancy in mares, number of ovarian follicles was monitored ultrasonically during different stages of the first trimester of pregnancy in 36 thoroughbred mares. From 9 of 36 mares, blood samples were collected weekly from the mating day till the end of the first trimester of pregnancy and plasma IGF-I profiles were examined with other hormones, like follicle stimulating hormone (FSH), luteinizing hormone (LH), ir-inhibin, progesterone and estradiol-17beta. Plasma IGF-I level fluctuated throughout the studied period with four peaks on the 7th, 28th, 49th and 84th days of pregnancy. Plasma IGF-I showed a positive correlation with plasma FSH (P<0.05), whereas no correlation was found with other hormones during the studied period. Plasma IGF-I had no correlation with the foetal size, but positive correlation with the number of large (> 30 mm) and medium (10-30 mm) follicles. These results suggested that IGF-I might produce from the medium and large follicles during early pregnancy and promote to develop their growth via pituitary FSH mediated effects in the mares.

Derar R, Haramaki S, Hoque S, et al. Insulin-like growth factor-I as a follicular growth promoter during early pregnancy in thoroughbred mares. J Vet Med Sci. 2005;67(1):19-23.

Insulin-like growth factor-1 (IGF-1) plays an important role in cell proliferation and differentiation. The purpose of this study was to use a radioreceptor assay to evaluate whether IGF-1 receptors are present in human pulp and to determine whether differences in its expression are found in the pulp tissue of teeth having incomplete or complete root development. Twenty pulps were obtained from freshly extracted human third molars; they were then processed and labeled with I-IGF-1. The results showed IGF-1 receptor expression in all human pulp samples. t test revealed statistically significant higher expression in the pulps from teeth having incomplete root development (P <0.005). Given the functions of this growth factor system in other tissues, the present findings are consistent with the hypothesis that IGF-1 contributes toward forming and mineralizing dental tissues as well as in pulp-repairing processes.

Caviedes-bucheli J, Muñoz HR, Rodríguez CE, Lorenzana TC, Moreno GC, Lombana N. Expression of insulin-like growth factor-1 receptor in human pulp tissue. J Endod. 2004;30(11):767-9.

Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Hyperinsulinemia and insulin action were initially proposed as the common preceding factors of hypertension, low high-density lipoprotein cholesterol, hypertriglyceridemia, abdominal obesity, and altered glucose tolerance, linking all these abnormalities to the development of coronary heart disease. The similarities of insulin resistance with another inflammatory state, atherosclerosis, have been described only in the last few decades. Atherosclerosis and insulin resistance share similar pathophysiological mechanisms, mainly due to the actions of the two major proinflammatory cytokines, TNF-alpha and IL-6. Genetic predisposition to increased transcription rates of these cytokines is associated with metabolic derangement and simultaneously with coronary heart disease. Dysregulation of the inflammatory axis predicts the development of insulin resistance and type 2 diabetes mellitus. The knowledge of how interactions between metabolic and inflammatory pathways occur will be useful in future therapeutic strategies. The effective administration of antiinflammatory agents in the treatment of insulin resistance and atherosclerosis is only the beginning of a promising approach in the management of these syndromes.

Fernández-real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev. 2003;24(3):278-301.

Human IGF-I is a single chain 70-amino acid polypeptide cross-linked by 3 disulfide bridges, with a calculated molecular mass of 7.6 kD. The IGF1 protein displays homology to proinsulin. The IGF-I structural gene maps locus 12q22-q24.1.The IGF-I coding region is flanked by sequences encoding an amino-terminal peptide of at least 25 residues and a carboxyl-terminal peptide of 35 amino acids. The findings provided evidence that IGF-I is synthesized as a precursor protein that undergoes proteolytic processing at both ends.

Insulin like growth factor 1 (IGF-1) and its receptor (IGF-1R) provide a potent proliferative signaling system that stimulates growth in many different cell types and blocks apoptosis. In vivo IGF-1 acts as an intermediate of many growth hormone responses, and may stimulate the growth of some types of cancer. IGF-1 also provides a mitogenic signal to act as a growth factor for many tissue culture cells. One component of IGF-1 mitogenic signaling is association of the receptor tyrosine kinase with Shc, Grb2, and Sos-1 to activate ras and the Map kinase cascade (raf, Mek, Erk). An endpoint of the Map kinase pathway is modification of transcription factor activity, such as activation of ELK transcription factors. Serum response factor (SRF) and AP-1 contribute to mitogenic signaling by many factors. Phosphorylation of IRS-1 and PI3 kinase activation are also involved in IGF-1 signaling, similar to insulin signaling.