Lost in translation: endoplasmic reticulum stress and the decline of <i>β</i>‐cell health in diabetes mellitus

Evans‐Molina, Carmella; Hatanaka, Masayuki; Mirmira, Raghavendra G.

doi:10.1111/dom.12163

Cited by 55 publications

(42 citation statements)

References 103 publications

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“…Glucotoxic, lipotoxic, and inflammatory conditions reduce the protein folding capacity of the ER, resulting in the accumulation and aggregation of unfolded proteins, a condition referred to as ER stress 191 . Myriad pathological factors in a diabetic milieu perturb ER function and cause ER stress 192 . Thus, β-cells have evolved to elicit a multi-faceted and complex signaling cascade to mitigate stress.…”

Section: Er Stressmentioning

confidence: 99%

Natural history of β-cell adaptation and failure in type 2 diabetes

Alejandro

Gregg

Blandino-Rosano

et al. 2015

Molecular Aspects of Medicine

194

121

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Type 2 diabetes mellitus (T2D) is a complex disease characterized by β-cell failure in the setting of insulin resistance. The current evidence suggests that genetic predisposition, and environmental factors can impair the capacity of the β-cells to respond to insulin resistance and ultimately lead to their failure. However, genetic studies have demonstrated that known variants account for less than 10% of the overall estimated T2D risk, suggesting that additional unidentified factors contribute to susceptibility of this disease. In this review, we will discuss the different stages that contribute to the development of β-cell failure in T2D. We divide the natural history of this process in three major stages: susceptibility, β-cell adaptation and β-cell failure and provide an overview of the molecular mechanisms involved. Further research into mechanisms will reveal key modulators of β-cell failure and thus identify possible novel therapeutic targets and potential interventions to protect against β-cell failure.

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Section: Er Stressmentioning

confidence: 99%

Natural history of β-cell adaptation and failure in type 2 diabetes

Alejandro

Gregg

Blandino-Rosano

et al. 2015

Molecular Aspects of Medicine

194

121

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“…The impression one obtains from these findings is that the process of generation of the peptidepositive-crinophagic-granules is taking place also constitutively, albeit increased by high glucose. We expect that as active diabetogenesis ensues this process may be modulated, such as a result of the stress conditions that accompanies diabetogenesis (38)(39)(40). The issue from the perspective of autoimmunity is that the insulin catabolic products constitute the immunogens that select for autoreactive T cells that bypass insulin processing and escape thymus regulation (5,23).…”

Section: Live Imaging Of Beta Cells and Apcs And Electron Microscopy mentioning

confidence: 99%

Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells

Vomund

Zinselmeyer

Hughes

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Beta cells from nondiabetic mice transfer secretory vesicles to phagocytic cells. The passage was shown in culture studies where the transfer was probed with CD4 T cells reactive to insulin peptides. Two sets of vesicles were transferred, one containing insulin and another containing catabolites of insulin. The passage required live beta cells in a close cell contact interaction with the phagocytes. It was increased by high glucose concentration and required mobilization of intracellular Ca 2+ . Live images of beta cell-phagocyte interactions documented the intimacy of the membrane contact and the passage of the granules. The passage was found in beta cells isolated from islets of young nonobese diabetic (NOD) mice and nondiabetic mice as well as from nondiabetic humans. Ultrastructural analysis showed intraislet phagocytes containing vesicles having the distinct morphology of dense-core granules. These findings document a process whereby the contents of secretory granules become available to the immune system. autoimmune diabetes | autoimmunity | insulin reactivity | insulin-reactive T cells

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“…A large number of ER stress review articles focusing on cancer [16][17][18][19][20][21][22][23][24]; Alzheimer disease [25][26][27][28][29]; Parkinson [30,31], kidney [32][33][34], lung [35][36][37], cardiovascular [38][39][40][41][42], and inflammatory diseases [43][44][45][46][47]; obesity [48][49][50]; gastrointestinal disease [51]; and diabetes [50,[52][53][54][55][56][57][58][59][60] have recently been published. In addition, relationships between ER stress and environmental toxicants have also been summarized [61,62].…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress in Drug- and Environmental Toxicant-Induced Liver Toxicity

Chen

Melchior

Guo

2014

Journal of Environmental Science and Health, Part C

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Liver injury resulting from exposure to drugs and environmental chemicals is a major health problem. Endoplasmic reticulum stress (ER stress) is considered to be an important factor in a wide range of diseases, such as cancer, neurological and cardiovascular disease, diabetes, and inflammatory diseases. The role of ER stress in drug-induced and environmental toxicant-induced liver toxicity has been underestimated in the past; emerging evidence indicates that ER stress makes a substantial contribution to the pathogenesis of drug-induced liver toxicity. In this review, we summarize current knowledge on drugs and environmental toxicants that trigger ER stress in liver and on the underlying molecular mechanisms. We also discuss experimental approaches for ER stress studies.

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Lost in translation: endoplasmic reticulum stress and the decline of β‐cell health in diabetes mellitus

Cited by 55 publications

References 103 publications

Natural history of β-cell adaptation and failure in type 2 diabetes

Natural history of β-cell adaptation and failure in type 2 diabetes

Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells

Endoplasmic Reticulum Stress in Drug- and Environmental Toxicant-Induced Liver Toxicity

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