An Integrative Network Biology Approach to Evaluate the Role of Endoplasmic Reticulum Stress Response in Obese Type 2 Diabetes

摘要

Extracellular/intracellular stimuli can influence eukaryotic cell function through organelles that regulate critical signaling pathways. The endoplasmic reticulum (ER), for example, impacts cellular processes including protein synthesis, folding and secretion; amino acid transport; apoptosis; cell proliferation; lipid synthesis across major cell types in response to stimuli such as accumulation of misfolded proteins and glucose deprivation. Dysregulated signaling pathways underlying the ER-mediated processes mentioned above have been linked to disease conditions such as diabetes, obesity, and Alzheimer's disease. Our current understanding, however, lacks a detailed network view that integrates organelle-mediated pathway dysregulation with cellular processes and disease pathogenesis. In this report, we introduce an integrative network biology approach that combines ER-stress response pathways with basic cellular processes using data from peer-reviewed literature. As an example, we apply our systems biology approach to study the role of ER stress in pancreaticβcells under obese diabetic conditions, generate testable hypotheses, and provide novel insights intoβ-cell pathogenesis.