Insulin-like growth factor I

Insulin-like Growth Factor I (IGF-I), also known as somatomedin C, is a protein that in humans is encoded by the IGF1 gene. IGF-I is primarily produced in the liver as a result of stimulation by growth hormone (GH). It plays an important role in childhood growth and continues to have anabolic effects in adults. IGF-I is a part of the Insulin-like growth factor system, which also includes the Insulin-like Growth Factor II (IGF-II), the IGF-I receptor (IGF1R), and a variety of binding proteins that regulate IGF-I's actions.

Structure and Function

IGF-I is a single chain polypeptide of 70 amino acids with a molecular weight of about 7.6 kDa. It shares a high degree of sequence similarity with insulin and has insulin-like activities, but its effects are distinguished by its growth-promoting properties. The molecule consists of an A chain, a B chain, and a C chain (the latter is not present in insulin), which are connected by disulfide bonds. IGF-I binds to the IGF1 receptor and to insulin-like growth factor-binding proteins (IGFBPs), which regulate its activity and extend its half-life in circulation.

Biological Role

IGF-I plays a crucial role in muscle growth, bone growth, and the development of the nervous system. It stimulates the proliferation of chondrocytes (cartilage cells), leading to bone growth, and promotes the differentiation and proliferation of myoblasts, contributing to muscle growth. In the nervous system, IGF-I supports neuronal survival, neurogenesis, and synaptogenesis, enhancing cognitive functions and neural repair mechanisms.

Clinical Significance

Abnormal levels of IGF-I are associated with a variety of health conditions. Low levels of IGF-I can lead to growth hormone deficiency and dwarfism, while high levels may indicate acromegaly or gigantism, conditions characterized by excessive growth and other physical abnormalities, usually due to a pituitary gland tumor producing excess GH. IGF-I also plays a role in aging, cancer, and diabetes mellitus, with its levels correlating with disease progression and prognosis in some cases.

Therapeutic Applications

Recombinant IGF-I has been explored as a potential treatment for growth failure and for conditions such as Laron syndrome, a rare form of dwarfism caused by GH receptor deficiency. It has also been investigated for its potential in treating neuromuscular diseases, diabetes, and neurodegenerative diseases due to its anabolic and regenerative properties.

Regulation

The production and activity of IGF-I are regulated by growth hormone (GH), nutritional status, and by a family of six high-affinity insulin-like growth factor-binding proteins (IGFBPs) and several low-affinity binding proteins. These binding proteins can inhibit or enhance the actions of IGF-I by modulating its interaction with its receptor and by controlling its bioavailability.