The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death

Yin, Jiajing; Li, Yanbo; Wang, Yan; Liu, Guodong; Wang, Jun; Zhu, Xingjun; Pan, Shangha

doi:10.4161/auto.8.2.18807

Cited by 57 publications

(41 citation statements)

References 77 publications

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“…In fact, transgenic mice lacking autophagy in their b-cells exhibit decreased b-cell mass and an aberrant response to glucose stimulation. Moreover, inhibition of autophagy increases the vulnerability of b-cells to cytotoxic effects (Yin et al, 2012). It has therefore been suggested that autophagy is essential to maintain the structure, mass, and function of b-cells.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation, Protects Pancreatic -Cells from Apoptosis, and Prevents Type 2 Diabetes Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet

Abderrazak

Hadri

Bosc

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Intraperitoneal injection of arglabin (2.5 ng/g of body weight, twice daily, 13 weeks) into female human apolipoprotein E 2 gene knock-in (ApoE 2 Ki) mice fed a high-fat Western-type diet (HFD) reduced plasma levels of glucose and insulin by ∼20.0% 6 3.5% and by 50.0% 6 2.0%, respectively, in comparison with vehicletreated mice. Immunohistochemical analysis revealed the absence of active caspase-3 in islet sections from ApoE 2 Ki mice fed a HFD and treated with arglabin. In addition, arglabin reduced interleukin-1b (IL-1b) production in a concentration-dependent manner in Langerhans islets isolated from ApoE 2 Ki mice treated with lipopolysaccharide (LPS) and with cholesterol crystals. This inhibitory effect is specific for the inflammasome NOD-like receptor family, pyrin domain-containing 3 (NLRP3) because IL-1b production was abolished in Langerhans islets isolated from Nlrp3 2/2 mice. In the insulin-secreting INS-1 cells, arglabin inhibited, in a concentration-dependent manner, the maturation of pro-IL-1b into biologically active IL-1b probably through the inhibition of the maturation of procaspase-1 into active capsase-1. Moreover, arglabin reduced the susceptibility of INS-1 cells to apoptosis by increasing Bcl-2 levels. Similarly, autophagy activation by rapamycin decreased apoptosis susceptibility while autophagy inhibition by 3-methyladenin treatment promoted apoptosis. Arglabin further increased the expression of the autophagic markers Bcl2-interacting protein (Beclin-1) and microtubule-associated protein 1 light chain 3 II (LC3-II) in a concentration-dependent manner. Thus, arglabin reduces NLRP3-dependent inflammation as well as apoptosis in pancreatic b-cells in vivo and in the INS-1 cell line in vitro, whereas it increases autophagy in cultured INS-1 cells, indicating survival-promoting properties of the compound in these cells. Hence, arglabin may represent a new promising compound to treat inflammation and type 2 diabetes mellitus development.

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Section: Resultsmentioning

confidence: 99%

Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation, Protects Pancreatic -Cells from Apoptosis, and Prevents Type 2 Diabetes Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet

Abderrazak

Hadri

Bosc

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…Another study reported marked autophagy induction during treatment of human pancreatic islets with palmitic acid, but not with glucose [140]. Thus far, relatively little is known about the exact interplay between autophagy and ER stress, but most of the evidence is in favor of targeting autophagy as a protective mechanism of b-cells to ameliorate ER stress [141].…”

Section: Diabetesmentioning

confidence: 99%

Stress-induced self-cannibalism: on the regulation of autophagy by endoplasmic reticulum stress

Deegan

Saveljeva

Gorman

et al. 2012

Cell. Mol. Life Sci.

242

170

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Macroautophagy (autophagy) is a cellular catabolic process which can be described as a self-cannibalism. It serves as an essential protective response during conditions of endoplasmic reticulum (ER) stress through the bulk removal and degradation of unfolded proteins and damaged organelles; in particular, mitochondria (mitophagy) and ER (reticulophagy). Autophagy is genetically regulated and the autophagic machinery facilitates removal of damaged cell components and proteins; however, if the cell stress is acute or irreversible, cell death ensues. Despite these advances in the field, very little is known about how autophagy is initiated and how the autophagy machinery is transcriptionally regulated in response to ER stress. Some three dozen autophagy genes have been shown to be required for the correct assembly and function of the autophagic machinery; however; very little is known about how these genes are regulated by cellular stress. Here, we will review current knowledge regarding how ER stress and the unfolded protein response (UPR) induce autophagy, including description of the different autophagy-related genes which are regulated by the UPR.

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“…These findings suggest that ER stress might be upstream of oxidant stress in hypertension. In addition, ER stress is often associated with autophagy (15), and the relevance of this for cells in the SFO is unknown. Finally, ER stress in pathological settings is usually associated with apoptotic cell death.…”

Section: Figurementioning

confidence: 99%

Endoplasmic reticulum stress and hypertension — a new paradigm?

Hasty¹,

Harrison²

2012

J. Clin. Invest.

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The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death

Cited by 57 publications

References 77 publications

Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation, Protects Pancreatic -Cells from Apoptosis, and Prevents Type 2 Diabetes Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet

Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation, Protects Pancreatic -Cells from Apoptosis, and Prevents Type 2 Diabetes Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet

Stress-induced self-cannibalism: on the regulation of autophagy by endoplasmic reticulum stress

Endoplasmic reticulum stress and hypertension — a new paradigm?

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