Inositol phosphoglycan (IPG)

Inositol phosphoglycans (IPGs) are a class of second messengers that play a critical role in the non-canonical insulin signaling pathway [1, 2]. They are generated through the hydrolysis of glycosyl-phosphatidylinositol (GPI) precursors in the cell membrane upon insulin receptor activation [3, 7]. There are two primary types: IPG-A, which contains myo-inositol and inhibits adenylyl cyclase and protein kinase A, and IPG-P, which contains D-chiro-inositol and activates pyruvate dehydrogenase phosphatase [1, 5]. Together, these molecules mimic and mediate the metabolic actions of insulin, such as stimulating glucose uptake, promoting glycogen synthesis, and regulating lipid metabolism [4, 9]. Deficiencies or imbalances in IPG production are strongly linked to insulin resistance, type 2 diabetes, and polycystic ovary syndrome (PCOS) [5, 13]. Consequently, IPGs and their precursors, such as D-chiro-inositol and myo-inositol, are targeted in therapeutic strategies to restore insulin sensitivity and manage metabolic disorders [8, 14].

Other names

Inositol phosphate glycanGlycosyl-phosphatidylinositol-derived mediatorPIG-PPhosphoinositolglycan-peptide

Inositol phosphoglycans act as insulin-mimetic second messengers that are released from the cell membrane in response to insulin receptor activation [1, 2]. IPG-P (containing D-chiro-inositol) activates pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase to enhance oxidative glucose metabolism, while IPG-A (containing myo-inositol) inhibits adenylyl cyclase and protein kinase A to regulate lipolysis [1, 5]. They also allosterically activate phosphoprotein phosphatase 2C-alpha (PP2Cα), leading to the stimulation of glycogen synthase and increased glucose uptake [2, 3].