Elucidating Vascular Neuropilin 1 (NRP1) Functions in Response to Novel Interactions with Insulin Substrates

阐明血管神经毡蛋白 1 (NRP1) 对与胰岛素底物的新相互作用的反应功能

• 批准号: 10550186
• 负责人: Ye Ding
• 金额: $ 39万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10550186
• 关键词: Adipocytes; Adipose tissue; Aorta; Attenuated; Binding; Binding Sites; Blood Vessels; Cancer cell line; Cardiovascular Diseases; Cell Line; Cells; Cholesterol; Cytoplasm; Cytoplasmic Tail; Diet; Disease; Docking; Dose; Endothelium; Epidermal Growth Factor Receptor; Extracellular Domain; Fluorescein-5-isothiocyanate; Functional disorder; Glucose tolerance test; Glycoproteins; Growth Factor; Hemostatic function; Hepatocyte; High Fat Diet; High-Risk Cancer; Hypoxia; In Vitro; Incidence; Inflammatory Response; Insulin; Insulin Receptor; Insulin Resistance; Insulin-Like Growth Factor I; KDR gene; Knockout Mice; Label; Link; Lipids; Liver; MET gene; Malignant Neoplasms; Measurement; Mediating; Membrane; Metabolic; Metabolic syndrome; Metabolism; Mus; Muscle Fibers; Neuropilin-1; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Obesity; Pathologic; Phosphotransferases; Physiology; Play; Process; Proteins; Public Health; Receptor Protein-Tyrosine Kinases; Role; Signal Pathway; Signal Transduction; Site; Testing; Time; Tissues; Transfection; Triglycerides; Tumor Angiogenesis; United States; Up-Regulation; angiogenesis; blood glucose regulation; comorbidity; epidemiologic data; in vivo; insight; insulin receptor substrate 1 protein; insulin tolerance; metabolic abnormality assessment; mouse model; novel; protein expression; receptor; response; vascular contributions

Project Summary/Abstract Obesity is emerging a major public health challenge in the United States, and around the world. It correlates with several comorbidities including, cardiovascular diseases and metabolic syndromes. Additionally, epidemiological data suggest strong links between obesity and cancer; however, mechanistic connections between obesity and these pathological conditions remain incomplete. Specifically, insulin resistance is characterized by attenuated whole-body sensitivity to insulin and may result in elevated levels of circulating free fatty acids (FFAs). Essential metabolic functions and signaling pathways under this condition becomes dysregulated, and alter finely-tuned regulation of glucose, lipid and overall energy hemostasis. Therefore, obesity is central to preventable pathological conditions due to direct instigation of metabolic perturbations and associated inflammatory responses. Importantly, elucidating novel metabolic, as well as angiogenic regulators may provide unique insight of disease conditions, such as cardiovascular diseases and cancer that depend on these processes. Studies on metabolism and cellular energetics have included skeletal muscles, adipose and hepatic cells given prominent roles these tissues play with respect to lipid utilization and storage. However, the response or contributions of vascular targets with respect to metabolic syndromes, including obesity- instigated perturbations remain unclear. At the nexus of proposed `vascular response target' is transmembrane, neuropilin-1 (Nrp1) receptor. We hypothesize that obesity and concomitant increase of circulating FFAs promote the expression and interaction of Nrp1 with insulin substrates, which vascular Nrp1 functions.

项目总结/文摘