Dissecting the Heterogeneity of Human Islet Stress Responses in Type 2 Diabetes

Abstract

The overall objective of this project is to dissect the genetic regulation of islet stress responses and to determine how genetic variants, including those associated with type 2 diabetes (T2D SNPs), modulate these responses to contribute to islet dysfunction and T2D pathogenesis. This project will address significant gaps in our knowledge of the genetic and cellular heterogeneity of T2D by 1) defining the precise transcriptomic and epigenomic alterations in islets associated with diabetogenic oxidative/metabolic and inflammatory stressors; 2) determining how each islet cell type responds to each stressor; 3) identifying individual genetic variants, particularly T2D SNPs, that modulate these responses to increase or decrease diabetes susceptibility; and 4) testing whether the genes and pathways induced by these stressors are compensatory/protective or pathogenic.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2019
Accession Number
AD1086480

Entities

People

  • Michael L Stitzel

Organizations

  • Jackson Laboratory

Tags

DTIC Thesaurus Topics

  • Antigens
  • Biomedical Research
  • Cell Line
  • Cells
  • Chromosome Structures
  • Cytokines
  • Diabetes
  • Diseases And Disorders
  • Dysfunction
  • Gene Expression
  • Genetic Phenomena
  • Genetics
  • Governments
  • Heterogeneity
  • Humanities
  • Insulin
  • Medical Personnel
  • Oxidative Stress
  • Pathogenesis
  • Procurement
  • Professional Development
  • Proteins
  • Regulations
  • Steady State
  • Stress (Physiology)
  • Tissue Donors
  • Training
  • Type 2 Diabetes

Fields of Study

  • Biology

Readers

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  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology