Nutritional Regulation of the Insulin-Like Growth Factors*

Abstract

Nutrition is one of the main regulators of circulating IGF-I. In humans, serum IGF-I concentrations are markedly lowered by energy and/or protein deprivation. Both energy and proteins are critical in the regulation of serum IGF-I concentrations. Indeed, after fasting, optimal intake of both energy and protein is necessary for the rapid restoration of circulating IGF-I. We believe, however, that in adult humans energy may be somewhat more important than protein in this regard. While the lowest protein intake is able to increase IGF-I in the presence of adequate energy, there is a threshold energy requirement below which optimal protein intake fails to raise IGF-I after fasting. When energy intake is severely reduced, the carbohydrate content of the diet is a major determinant of responsiveness of IGF-I to GH. The essential amino acid content of the diet is also critical for the optimal restoration of IGF-I after fasting, when protein intake is reduced. The exquisite sensitivity of circulating IGF-I to nutrients, the nycthemeral stability of its concentrations and its relative short half-life constitute the basis for its use as a marker of both nutritional status and adequacy of nutritional rehabilitation. For these indications, IGF-I measurement is more sensitive and more specific than measurement of the other nutrient-related serum proteins (albumin, prealbumin, transferrin, retinol-binding protein). Animal models have been developed to investigate the mechanisms responsible for the nutritional regulation of IGF-I. There is no doubt that many mechanisms are involved (Fig. 12). Decline of serum IGF-I in dietary restriction is independent of the diet-induced alterations in pituitary GH secretion. The role of the liver GH receptors is dependent on the severity of the nutritional insult. In severe dietary restriction (fasting), a marked decrease of the number of somatogenic receptors supports the role of a receptor defect in the decline of circulating IGF-I. In contrast, in less severe forms of dietary restriction (protein restriction), the decline of IGF-I results from a postreceptor defect in the GH action at the hepatic level. Nutritional deprivation decreases hepatic IGF-I production by diminishing IGF-I gene expression. Decline in IGF-I gene expression is mainly caused by nutrient deficiency and less importantly by the nutritionally induced hormonal changes (insulin and T3). Diet restriction also increases the clearance and degradation of serum IGF-I through changes in the levels of circulating IGFBPs.(ABSTRACT TRUNCATED AT 400 WORDS)

IGF-1 and risk of additional breast cancer in the WHEL study

“…It has been shown that insulin has a role in breast cancer incidence through stimulation of proliferation of breast cancer cells (Milazzo et al 1992, Mayer et al 2008. Insulin is central to regulation of IGF1 as well (Straus 1994, Thissen et al 1994. Insulin was also found to predict recurrence of breast cancer (Goodwin et al 2002), and in other studies, women with breast cancer and diabetes had a 40% increase in mortality within 5 years following diagnosis compared to women with breast cancer without diabetes (Lipscombe et al 2008); and breast cancer survivors with HbA1cR7.0% had a hazard ratio (HR) of 2.35; 95% CI, 1.56-3.54 in developing a second breast cancer compared with women with HbA1c!6.5% (Petridou et al 2000, Erickson et al 2010.…”

Differential Regulation of Insulin-like Growth Factor-I (IGF-I) Receptor Gene Expression by IGF-I and Basic Fibroblastic Growth Factor

“…In vivo, fasting was shown to increase IGF-I-specific binding in several tissues, and these changes in IGF-I binding were accompanied by a ϳ2-fold increase in IGF-IR mRNA abundance (3). Since, in some of the tissues, the local levels of IGF-I are decreased after a reduction in caloric intake, it is possible that the increases in IGF-IR expression are secondary to the decrease in local tissue IGF-I concentrations (4). In contrast, some growth disorders such as Laron-type dwarfism are associated with long term reductions of circulating levels of IGF-I.…”

Regulation of Insulin-like Growth Factor-I and -II by Glucose in Primary Cultures of Fetal Rat Hepatocytes

“…1 -I and -II are cell growth regulators that originate largely in the liver (1). Hepatic production of IGFs appears to be regulated at pretranslational levels, as indicated by the strong correlations between circulating IGFs and abundance of hepatic IGF-I and -II mRNA (2)(3)(4).…”

“…Hepatic production of IGFs appears to be regulated at pretranslational levels, as indicated by the strong correlations between circulating IGFs and abundance of hepatic IGF-I and -II mRNA (2)(3)(4). Secretion of both IGFs in adult animals is mainly regulated by growth hormone (GH), but nutritional status and serum insulin concentration are important factors involved in the regulation of IGF synthesis and secretion (1)(2)(3)(4). Previous work "in vivo" has shown that a balanced insulin/nutrients ratio regulates IGFs secretion during the perinatal period of the rat, when the IGF response to GH is not yet well established (2).…”

“…8B). DISCUSSION Experimental models in vivo have been widely used for the study of IGF regulation and have shown the important contribution of factors such as nutrients and insulin involved in liver IGF synthesis and secretion (1)(2)(3). Although the factors involved in the IGF regulation seem to be the same during the lifetime, the relative contribution is different depending on the stage of development (14).…”