Unexpected Systemic Phenotypes Result from Focal Combined Deficiencies of Forebrain Insulin Receptor/IGF-1 Receptor Signaling

Details

• Personal Author:
  Gandy S ; Huffman DM
• Description:
  Midlife obesity has recently been identified as a global pandemic. Morbidities and mortalities attributable to excess adiposity include atherosclerosis, type 2 diabetes (T2D) (2), certain cancers, and dementia, each of which has reached epidemic proportions on its own. It is no exaggeration to state that T2D and dementia threaten the emotional and financial stabilities of most Western economies. Moreover, when T2D and dementia comorbidity is present, the severities and costs of management of each are dramatically increased. Thus, there are major imperatives that drive current inquiries into the borderland where cognition and metabolism intersect. New research in PNAS by Soto et al. provides significant insight into this area by describing dramatic links to phenotypes relevant to cognition, behavior, and metabolism. A key set of principles drove this work: (i) insulin receptors (IRs) and insulin-like growth factor 1 (IGF-1) receptors (IGF1Rs), upon binding of their cognate ligand, trigger two closely related signaling pathways that promote both redundant and distinct intracellular effects (7), and (ii) this redundancy includes the formation of IR/IGF1R hybrids, and it has been estimated that at least half of the IRs and IGF1Rs in brain exist as heterodimers (8), which have greatest affinity for IGF-1 and IGF-2. [Description provided by NIOSH]
• Subjects:
  Behavior Blood Energy Metabolism Hematologic Diseases Mental Disorders Mental Health Morbidity Mortality Neoplasms Nervous System Occupational Health Safety

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• Keywords:
  Blood Sugar Disorders Brain Disorders Brain Function Cancer Cognitive Function Humans Mental Disorders Metabolism Morbidity Rates Mortality Rates Obesity

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• ISSN:
  0027-8424
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  116
• Issue:
  13
• NIOSHTIC Number:
  nn:20055752
• Citation:
  Proc Natl Acad Sci U.S.A. 2019 Mar; 116(13):5852-5854
• Federal Fiscal Year:
  2019
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20160901
• Source Full Name:
  Proceedings of the National Academy of Sciences of the United States of America
• End Date:
  20200831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:acda7144d8d54827ade801aafbc79f6b45db37dd564e61c790d1de9e8e0d6a4f079d8414f785d306387a3d9a48af8dde0b9adaedc17695e88209d4144b28a5f7
• Download URL:
  https://stacks.cdc.gov/view/cdc/213533/cdc_213533_DS1.pdf
• File Type:
  [PDF - 649.46 KB ]