From immunobiology to β-cell biology: The changing perspective on type 1 diabetes

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Type 1 Diabetes (T1D) is characterized by the immune mediated destruction of β cells. Clinical studies have focused on drug therapies to modulate autoimmunity, yet none of these interventions has resulted in durable preservation of β-cell function. These findings raise the possibility that initiating or propagating events outside of the immune system should be considered in future efforts to prevent or reverse T1D. An emerging concept suggests that defects inherent to the β cell may trigger autoimmunity. A study by Engin et al. in type 1 diabetic NOD mice suggests that excessive β-cell endoplasmic reticulum stress arising from environmental insults results in abnormal protein synthesis, folding, and/or processing. Administration of the chemical protein folding chaperone TUDCA resulted in recovery of β-cell endoplasmic reticulum function and a diminished incidence of diabetes in NOD mice. We propose here that these data and others support a model whereby an inadequate or defective β-cell endoplasmic reticulum response results in the release of β-cell antigens and neoantigens that initiate autoimmunity. Pharmacologic therapies that either mitigate these early β-cell stressors or enhance the ability of β cells to cope with such stressors may prove to be effective in the prevention or treatment of T1D.

Original languageEnglish (US)
Article numbere28778
Pages (from-to)e28778-1-e28778-5
JournalIslets
Volume6
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Type 1 Diabetes Mellitus
Cell Biology
Autoimmunity
Inbred NOD Mouse
Protein Folding
Endoplasmic Reticulum
Endoplasmic Reticulum Stress
Immune System
Antigens
Drug Therapy
Incidence
Therapeutics

Keywords

  • ATF6
  • Autoimmunity
  • ER stress
  • SXBP1
  • Type 1 diabetes
  • Unfolded protein response
  • β cell

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

From immunobiology to β-cell biology : The changing perspective on type 1 diabetes. / Maganti, Aarthi; Evans-Molina, Carmella; Mirmira, Raghu.

In: Islets, Vol. 6, No. 2, e28778, 2014, p. e28778-1-e28778-5.

Research output: Contribution to journalArticle

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