Abstract
Diabetes is one of the most prevalent diseases in the world. Type 1 diabetes is characterized by the failure of synthesizing and secreting of insulin because of destroyed pancreatic β-cells. Type 2 diabetes, on the other hand, is described by the decreased synthesis and secretion of insulin because of the defect in pancreatic β-cells as well as by the failure of responding to insulin because of malfunctioning of insulin signaling. In order to understand the signaling mechanisms of responding to insulin, it is necessary to identify all components in the insulin signaling network. Here, an interaction network consisting of proteins that have statistically high probability of being biologically related to insulin signaling in Homo sapiens was reconstructed by integrating Gene Ontology (GO) annotations and interactome data. Furthermore, within this reconstructed network, interacting proteins which mediate the signal from insulin hormone to glucose transportation were identified using linear paths. The identification of key components functioning in insulin action on glucose metabolism is crucial for the efforts of preventing and treating type 2 diabetes mellitus.
Highlights
Signaling provides the communication of living cells by processing biological information
The phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B (PKB) pathway is responsible for the metabolic actions of the insulin such as glucose uptake, glycogen synthesis, gene expression, and protein synthesis
This study provides a comprehensive insulin signaling network with indication of key components which will facilitate a deeper understanding of underlying mechanisms of insulin-resistant states and pathophysiology of insulin deficiency
Summary
Signaling provides the communication of living cells by processing biological information. Using systematic genome-wide and pathway specific proteinprotein interaction screens, a framework of the interconnectivity of a large number of human proteins, including therapeutically relevant disease-associated proteins has been generated by these pathways Recent developments in these protein-protein interaction networks have increased the understanding of the mechanisms of diseases with identification of drug targets and adaptation of living cells to the environment [1,2,3,4,5]. Beside its primary role in glucose homeostasis, insulin signaling mechanism regulates ion and amino acid transport, lipid metabolism, glycogen synthesis, gene transcription and mRNA turnover, protein synthesis and degradation, and DNA synthesis by a complex, highly integrated network activated by the insulin receptor [6, 9]
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