ER stress increases expression of intracellular calcium channel RyR1 to modify Ca2+ homeostasis in pancreatic beta cells

Zhang, Irina X; Hermann, Andrea; Leon, Juan; Jeyarajan, Sivakumar; Arunagiri, Anoop; Arvan, Peter; Gilon, Patrick; Satin, Leslie S.

doi:10.1016/j.jbc.2023.105065

Cited by 6 publications

(2 citation statements)

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“…Dysfunction: Perturbations in RyR expression and/or function during the pathogenesis of diabetes have been shown to play a role in disrupting Ca 2+ ER and cytoplasmic Ca 2+ handling. Under conditions of protein misfolding and associated ER stress, RyR1 expression is significantly increased in INS-1, leading to Ca 2+ ER release, enhanced β-cell UPR, and increased apoptosis [ 56 , 61 ] ( Figure 2 ). Thus, the inhibition of RyRs in INS-1 cells and mouse islets prevents tunicamycin-induced Ca 2+ ER depletion in β-cells [ 56 ].…”

Section: Ca 2+ Er Handling Proteins And...mentioning

confidence: 99%

Disrupted Endoplasmic Reticulum Ca2+ Handling: A Harβinger of β-Cell Failure

Dobson,

Jacobson

2024

Biology

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The β-cell workload increases in the setting of insulin resistance and reduced β-cell mass, which occurs in type 2 and type 1 diabetes, respectively. The prolonged elevation of insulin production and secretion during the pathogenesis of diabetes results in β-cell ER stress. The depletion of β-cell Ca2+ER during ER stress activates the unfolded protein response, leading to β-cell dysfunction. Ca2+ER is involved in many pathways that are critical to β-cell function, such as protein processing, tuning organelle and cytosolic Ca2+ handling, and modulating lipid homeostasis. Mutations that promote β-cell ER stress and deplete Ca2+ER stores are associated with or cause diabetes (e.g., mutations in ryanodine receptors and insulin). Thus, improving β-cell Ca2+ER handling and reducing ER stress under diabetogenic conditions could preserve β-cell function and delay or prevent the onset of diabetes. This review focuses on how mechanisms that control β-cell Ca2+ER are perturbed during the pathogenesis of diabetes and contribute to β-cell failure.

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Section: Ca 2+ Er Handling Proteins And...mentioning

confidence: 99%

Disrupted Endoplasmic Reticulum Ca2+ Handling: A Harβinger of β-Cell Failure

Dobson,

Jacobson

2024

Biology

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“…Endoplasmic reticulum stress can restore the normal function of the endoplasmic reticulum through cellular autophagy. This process involves inducing cellular autophagy through unfolded proteins response (UPR) ( 27 ), promoting Ca 2+ influx into the cytoplasm to induce cellular autophagy ( 28 ), and inhibiting Bcl-2 to induce endoplasmic reticulum autophagy ( 29 ) ( Figure 4 ). The occurrence of autophagy has both positive and negative effects on the endoplasmic reticulum.…”

Section: Overview Of Autophagy In Diabetic Statesmentioning

confidence: 99%

The role of autophagy in the treatment of type II diabetes and its complications: a review

Zhao,

Bie,

Pang

et al. 2023

Front. Endocrinol.

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Type II diabetes mellitus (T2DM) is a chronic metabolic disease characterized by prolonged hyperglycemia and insulin resistance (IR). Its incidence is increasing annually, posing a significant threat to human life and health. Consequently, there is an urgent requirement to discover effective drugs and investigate the pathogenesis of T2DM. Autophagy plays a crucial role in maintaining normal islet structure. However, in a state of high glucose, autophagy is inhibited, resulting in impaired islet function, insulin resistance, and complications. Studies have shown that modulating autophagy through activation or inhibition can have a positive impact on the treatment of T2DM and its complications. However, it is important to note that the specific regulatory mechanisms vary depending on the target organ. This review explores the role of autophagy in the pathogenesis of T2DM, taking into account both genetic and external factors. It also provides a summary of reported chemical drugs and traditional Chinese medicine that target the autophagic pathway for the treatment of T2DM and its complications.

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