The functions of IGF-II are very diverse. IGF-II plays a role in the development of the embryo, it is an important mitogenic factor for growing cells, it is involved in differentiation processes and it is highly expressed in many tumor tissues. Because of its pivotal role in these diverse...

In prokaryotes and eukaryotes, genetic information is supported by doublestranded DNA, in which only one strand is usually transcribed in messenger RNA. Nevertheless, transcription could occur from both strands or from complementary strands, leading sometimes to the synthesis of complementary...

The insulin-like growth factor-I receptor (IGF-IR) has a central role in normal cellular proliferation as well as in transformation processes. Transcription factors have been identified that modulate the activity of the IGF-IR gene. Transcription factors with tumor suppressor activity, such as...

The type 1 insulin-like growth factor (IGF-I) receptor is a tyrosine kinase receptor, conserved through evolution in metazoans, from C. elegans to mammals. It displays several functions, some of which are seemingly contradictory. This Chapter examines only selected functions of the...

The IGF-1 receptor (IGF1R) gene is transcriptionally regulated by growth factors and tumor repressors and encodes a 210 kDa αβ chain which is proteolytically cleaved and disulfide bonded to produce an α 2 β 2 structure. IGF-1 binding to a cysteine-rich domain in the...

The metabolic effects of IGF-I are varied and remarkably similar in many respects to those of GH. IGF-I mediates some, but not all of the metabolic actions of GH in man. Both GH and IGF-I potently stimulate whole body protein synthesis rates in healthy subjects, with minimal effects...

Immune cell development and homeostasis is a highly coordinated process influenced by a network of cells and soluble factors. The endocrine system, in particular the insulin-like growth factors (IGFs), has been shown to play a key role in development and maintenance of normal immune...

Low circulating levels of insulin-like growth factor-I (IGF-I) and alterations in IGF-binding proteins (IGFBP-s) mark the catabolic state of critical illness. The origin of these changes appears different during the first hours to days after onset and in the more chronic phase of critical...

IGF actions are regulated by a family of six high affinity binding proteins (IGFBPs), some of which also have IGF-independent actions. The IGFBPs have highly conserved N- and C-domains, each of which contain internal disulfide links. The middle, 'linker' L-domains of the IGFBPs...

Apoptosis is a physiologically regulated mode of cell death, which plays a critical role during development and maturation. Apoptosis is tightly controlled both within the cell and by extracellular cues from soluble survival factors and from cell contacts with its extracellular environment. For...

In the last several years, investigators have begun to unravel the role of insulin like growth factor-I (IGF-I), and its family of IGF binding proteins, in the building and maintenance of the adult skeleton. Although it was nearly a half a century ago that the presence of a...

Insulin-like growth factor-I (IGF-I) is a small polypeptide growth factor that is ubiquitously present in physiologic fluids. IGF-I is a potent stimulant of extracellular matrix protein (ECM) synthesis by all connective tissue cell types and it can control synthesis of basement...

Bone formation is essential to all aspects of bone physiology, including growth, remodeling, and repair. In terms of potential messenger molecules that regulate bone formation, recent studies have provided strong evidence for a physiological role for IGFBP-5 in the regulation of bone...

Breast cancer remains one of the most common causes of mortality in women worldwide, despite intensive research aimed at identifying the factors involved in its establishment and progression. Many lines of evidence support a key role for the IGF system in the development and...

Insulin-like growth factors (IGFs), IGF receptors and IGF-binding proteins (IGFBPs) are expressed in epithelial cancer. The IGF system is involved in the regulation of the proliferation of both normal and malignant epithelial cells. Proliferative effects of IGFs are mediated...

The insulin-like growth factors, IGF-I and IGF-II, comprise a pair of structurally related, secreted proteins which control diverse cellular functions by regulating multiple signal transduction pathways. Gene targeting experiments have revealed essential roles for IGF action in normal...

Insulin-like growth factor-I (IGF-I) mRNAs is expressed in adults principally in liver, which secretes IGF-I to act as an endocrine growth factor. Liver IGF-I mRNAs are transcribed from multiple start sites within two promoters, giving rise to mRNAs containing either exon 1 or exon 2...

Epidemiologic studies that simply observe the natural cause of events often are referred to as observational studies. In contrast, studies in which the investigator intervenes to change some participants' behavior, assigning the exposure status of each participant, are referred to as...

The insulin-like growth factors-I and -II (IGF-I and IGF-II) are neurotrophic factors with sequence homology to pro-insulin. Through the type I IGF receptor (IGF-IR), the IGFs mediate proliferation, survival and differentiation of neuronal and non-neuronal cells.1,2 IGFs are of particular...

Insulin-like growth factors (IGFs) and their receptors exert their effects on a variety of sarcomas through autocrine, paracrine and endocrine mechanisms. In addition to regulating the proliferation of normal as well as malignant cells of mesenchymal origin, IGFs and their receptors play a...

This review describes the multiple ways in which the kidney and the IGF-I system interact in both health and disease. IGF-I is an important physiological regulator of glomerular hemodynamics, renal growth and certain tubular functions. In several disease states the IGF-I system is an...

Extrapancreatic tumors associated with hypoglycemia (non-islet-cell tumor hypoglycemia, NICTH) is one of major causes of fasting hypoglycemia. In some patients with NICTH, insulin-like growth factor II (IGF-II) produced by and secreted from the tumor is thought to be a hypoglycemic agent....

The relationship between the sites of insulin-like Growth factor-I (IGF-I) expression and the sites of its growth promoting actions have been debated for years. There is compelling evidence for each potential mode of IGF-I action. Arguments for IGF-I endocrine actions include the findings...

Insulin-like growth factor-I (IGF-I) has effects on insulin-stimulated glucose metabolism, increasing peripheral glucose disposal and decreasing hepatic glucose output, thus enhancing insulin sensitivity, however, the mechanisms are poorly understood. It is thought that IGF-I may act...

The proposed “insulin-like growth factor binding protein (IGFBP) superfamily” is said to consist of the high affinity binding proteins, IGFBP-1 to -6 and low affinity binding proteins (IGFBP-related proteins). A key mechanism for regulating IGF bioactivities is the high-affinity IGFBPs,...

During the course of brain development, insulin-like growth factor (IGF1) and the IGF1 receptor are most highly expressed by maturing projection neurons during a time of rapid process growth and synaptogenesis. During this time, IGF1-expressing neurons grow the most extensive dendritic...

Normal and abnormal growth of mammary or breast epithelium is coordinately controlled by circulating hormones and locally-produced growth factors. The insulin-like growth factors and their primary signaling receptor, the IGF type I receptor, have demonstrated roles in normal mammary gland...

Insulin-like growth factor binding proteins (IGFBPs) modulate cell functions through IGF-dependent and independent mechanisms. The IGFBPs are subject to complex regulation, both inhibitory and stimulatory, by transforming growth factor-b (TGF-b) in various cell types, which may result in...

An up to-date description of the etiology, clinical and laboratory pathology of the Laron Syndrome (Primary GH resistance or insensitivity). is presented. Laron Syndrome is a unique model to study the physiological role of IGF-I(primary IGF-I deficiency ) and the IGF-I /GH relationship....

An important aspect of the IGF system in postnatal human physiology is its involvement in tumorigenesis. This was hardly unexpected, based upon the demonstrated role of IGF-I, in particular, as a potent growth regulator. Reports over the last several years of a strong association of...

Insulin and insulin-like growth factor signaling systems arose early in evolution and play key roles in regulating cellular proliferation and survival, energy utilization at both the cellular and whole organism levels, and body size and longevity. In higher organisms, more specific...

A cell and by extracellular cues from soluble survival factors and from cell contacts with its extracellular environment. For many cell types the most prevalent and potent survival factor is IGF-I. The family of six high affinity IGFBPs modulate the availability and hence the anti-apoptotic...

The type 1 insulin-like growth factor receptor (IGF-1R) is widely expressed across many cell types in fetal and postnatal tissues. Signalling through the IGF-1R is the principal pathway responsible for somatic growth in fetal mammals, while somatic growth in postnatal animals is achieved...