ADD-1 provides major new insight into the mechanism of insulin action
Year: 1999
Type: letter
Abstract: We evolved to live in a world in which food supplies are unpredictable in availability and often insufficient to meet immediate needs. Consequently, it is critical to be able to switch between the distinct metabolic programs that are appropriate to either the fasted or the fed state. Although many endocrine systems are involved in this transition, insulin is a preeminent hormonal mediator of this nutritional switch. Insulin levels rise postprandially to mediate anabolism and energy storage and fall between meals to permit the release of adipose energy stores and the switch from glucose use to production. The relevant actions of insulin take place in adipose tissue, muscle, and liver, where insulin receptor signaling exerts tissue-specific effects on an array of metabolic pathways that impact on carbohydrate, lipid, and protein metabolism. The cellular mechanism of insulin action has been a topic of major interest for many years. The greatest emphasis has been on the early steps of signal transduction, involving the insulin receptor substrate (IRS) proteins, which when tyrosine phosphorylated by the insulin receptor kinase serve as docking proteins for assembly of signaling complexes for downstream pathways such as ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and others (1). Many classic actions of insulin (e.g., glucose transport and glycogen synthesis) occur very rapidly and require the mediation of rapid changes in the state of protein phosphorylation or dephosphorylation. It is established that, alongside these rapid nongenomic effects, changes in gene expression play critical roles in insulin action in adipose cells, liver, and other tissues (2).
Authors: Jeffrey S. Flier, Anthony N. Hollenberg
Institutions: Beth Israel Deaconess Medical Center, Harvard University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2036381699