Book chapter
Inflammatory Pathways Linked to β Cell Demise in Diabetes
Islets of Langerhans, pp.989-1045
Springer Netherlands
04/17/2014
DOI: 10.1007/978-94-007-6686-0_30
Abstract
Inflammation is proposed to play a key role in the development of both type 1 diabetes (T1D) and type 2 diabetes (T2D). It is well established that autoimmunity against β cells is responsible for massive loss of β cells in T1D. Recently, it has been recognized that chronic low-grade inflammation is not limited to insulin target organs but is also seen in islets in T2D. In T1D, T lymphocytes are primed to destroy the β cells. However, the process that leads to the development of self-reactive T lymphocytes remains elusive and is an area of intense research. A complex interplay between genetic and environmental factors, β cells, and immune cells is likely involved in the process. Immunomodulatory therapies have been attempted with some promises in animal models of T1D but have not yielded satisfactory effects on humans. Recent initiatives to evaluate T1D pathology in human donor pancreata hold promise to increase our knowledge in the coming years. In T2D, overnutrition results in metabolic stress including glucolipotoxicity, endoplasmic reticulum stress, and oxidative stress that potentially trigger an inflammatory response in the islets. Substantial evidence exists for an increase in humoral inflammatory mediators and an accumulation of macrophages in the islets of T2D subjects. Anti-inflammatory therapies targeting IL-1β and NFkB have shown improvement in β cell functions in small short term studies of T2D humans, providing a proof of principle for targeting islet inflammation in T2D. However, the nature of islet inflammation in T2D needs better characterization to tailor anti-inflammatory therapies that are effective and durable for T2D.
Details
- Title: Subtitle
- Inflammatory Pathways Linked to β Cell Demise in Diabetes
- Creators
- Yumi Imai - Department of Internal Medicine, Eastern Virginia Medical School, Strelitz Diabetes Center, Norfolk, USAMargaret A Morris - Departments of Internal Medicine and Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Strelitz Diabetes Center, Norfolk, USAAnca D Dobrian - Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, USADavid A Taylor-Fishwick - Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, USAJerry L Nadler - Department of Internal Medicine, Eastern Virginia Medical School, Strelitz Diabetes Center, Norfolk, USA
- Resource Type
- Book chapter
- Publication Details
- Islets of Langerhans, pp.989-1045
- DOI
- 10.1007/978-94-007-6686-0_30
- Publisher
- Springer Netherlands; Dordrecht
- Language
- English
- Date published
- 04/17/2014
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094510902771
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