Details

Autor(en) / Beteiligte

• Clemmons, David

Titel

Role of IGF binding proteins in regulating IGF responses to changes in metabolism

Ist Teil von

• Journal of molecular endocrinology, 2018-07, Vol.61 (1), p.T139-T169

Ort / Verlag

England

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• The IGF binding protein family contains six members that share significant structural homology. Their principal function is to regulate the actions of IGF-I and IGF-II. These proteins are present in plasma and extracellular fluids and regulate access of both IGF-I and II to the type I IGF receptor. Additionally they have functions that are independent of their ability to bind IGFs. Each protein is regulated independently of IGF-I and IGF-II and this provides an important mechanism by which other hormones and physiologic variables can regulate IGF actions indirectly. Several members of the family are sensitive to changes in intermediary metabolism. Specifically the presence of obesity/ insulin resistance can significantly alter the expression of these proteins. Similarly changes in nutrition or catabolism can alter their synthesis and degradation. Multiple hormones such as glucocorticoids, androgens, estrogen and insulin regulate IGFBP synthesis and bioavailability. In addition to their ability to regulate IGF access to receptors these proteins can bind to distinct cell surface proteins or proteins in extracellular matrix and several cellular functions are influenced by these interactions. IGFBPs can be transported intracellularly and interact with nuclear proteins to alter cellular physiology. In pathophysiologic states there is significant dysregulation between the changes in IGFBP synthesis and bioavailability and changes in IGF-I and IGF-II. These discordant changes can lead to marked alterations in IGF action. Although binding protein physiology and pathophysiology are complex experimental results have provided an important avenue for understanding how IGF actions are regulated in a variety of physiologic and pathophysiologic conditions.