Autophagy and its link to type II diabetes mellitus

Yang, Jai Sing; Lu, Chi Cheng; Kuo, Sheng Chu; Hsu, Yu-Chin; Tsai, Shih Chang; Chen, Shih Yin; Chen, Yng Tay; Lin, Ying; Huang, Yu Chuen; Chen, Chao‐Jung; Lin, Wei; Liao, Wenlin; Lin, Wei Yong; Liu, Yu Huei; Sheu, Jinn Chyuan; Tsai, Fuu Jen

doi:10.1051/bmdcn/2017070201

Cited by 88 publications

(72 citation statements)

References 184 publications

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“…Autophagy regulates the function of insulin‐sensitive tissues such as skeletal muscle, liver, visceral fat, and subcutaneous fat, as well as islet β cells (Yang et al, ), while deficient autophagy will lead to the impairment of islet β‐cell function and mass, thus eventually leading to the incidence of diabetes (Marrif & Al‐Sunousi, ). Several signal pathways involving in the regulation of autophagy, such as AMPK/mTOR signal pathway, have been confirmed to play an important role in protecting islet β cells (Varshney, Gupta, & Roy, ).…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy is a highly conserved process to eliminate aged and miss‐folded proteins or damaged organelles for maintaining cellular homeostasis and promoting cell survival (Levine & Kroemer, ,; Zhang & Chen, ). The dysfunction of autophagy may induce a series of diseases, such as diabetes mellitus, cancer, aging‐related diseases, and neurodegenerative diseases (Chen & Karantza, ; Chen & Karantza‐Wadsworth, ; Fan et al, ; Kou & Chen, ; Yang et al, ). Deficient function of islet β cells is a major pathological features of diabetes mellitus, but autophagy plays an important role in regulating the structure and functions of β cells through clearing senescent cells and damaged proteins or organelles, and protecting islet β cells against apoptosis (Las & Shirihai, ).…”

Section: Introductionmentioning

confidence: 99%

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Metformin‐induced autophagy and irisin improves INS‐1 cell function and survival in high‐glucose environment via AMPK/SIRT1/PGC‐1α signal pathway

Jia

et al. 2019

Food Science & Nutrition

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In order to explore the protective function of metformin on pancreatic β cells to alleviate insulin resistance and underlying mechanisms, INS‐1 cells were cultured into normal control (N), high glucose (H), high glucose and metformin (H + Met), high glucose and chloroquine (H + CQ), and high glucose and Ex527 (H + Ex527) groups, respectively. Upon 24‐hr cultivation, the proliferation and glucose‐stimulated insulin secretion (GSIS) of INS‐1 cells were determined, and the expression of irisin and other proteins associated with AMPK/SIRT1/PGC‐1α signal pathway, autophagy, and apoptosis was evaluated. Compared with the N group, the cells from the H group revealed lower proliferation, GSIS, and expression of irisin and proteins associated with AMPK/SIRT1/PGC‐1α signal pathway and autophagy, but higher expression of proteins associated with apoptosis; in contrast, metformin could significantly rescue lower cell proliferation, GSIS, and expression of proteins associated with AMPK/SIRT1/PGC‐1α signal pathway and autophagy, as well as irisin, and suppress apoptosis in high‐glucose environment. Meanwhile, autophagy inhibitor CQ and SIRT1 inhibitor Ex527 can block above functions of metformin. Therefore, metformin can promote INS‐1 cell proliferation, enhance GSIS, and suppress apoptosis by activating AMPK/SIRT1/PGC‐1α signal pathway, up‐regulating irisin expression, and inducing autophagy in INS‐1 cells in high‐glucose environment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metformin‐induced autophagy and irisin improves INS‐1 cell function and survival in high‐glucose environment via AMPK/SIRT1/PGC‐1α signal pathway

Jia

et al. 2019

Food Science & Nutrition

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“…Induction of tumor cell apoptosis is one of the best strategies for treating glioma and multiple types of cancers (27,28). Apoptotic death can be activated by three main pathways (17,29). The extrinsic pathway is triggered through binding of extrinsic signals to death receptors, which leads to activation of caspase-8 (29,30).…”

Section: Discussionmentioning

confidence: 99%

“…Apoptotic death can be activated by three main pathways (17,29). The extrinsic pathway is triggered through binding of extrinsic signals to death receptors, which leads to activation of caspase-8 (29,30). The mitochondrial (intrinsic signaling) pathway is activated upon cellular stresses such as ROS production and ΔΨm disruption, and this results in activation of caspase-9.…”

Section: Discussionmentioning

confidence: 99%

Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells

Tsai¹,

Chen

Hsiao³

et al. 2018

Oncol Rep

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Gadolinium (Gd) compounds serve as magnetic resonance imaging contrast agents and exert certain anticancer activities. Yet, the molecular signaling underlying the antitumor effect of Gd chloride (GdCl 3) on glioma remains unclear. In the present study, we aimed to ascertain the apoptotic mechanisms of GdCl 3 on rat glioma C6 cells. Our results demonstrated that GdCl 3 significantly reduced cell viability and shrunk cell morphology of C6 cells in a concentration-dependent manner. GdCl 3 led to apoptotic C6 cell death as detected by TUNEL staining. An increase in cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9 occurred in GdCl 3-treated C6 cells as detected by immunoblotting analysis. The activities of caspase-3, caspase-8 and caspase-9 were increased, and the specific inhibitors of caspase-3/-8/-9 individually reversed cell viability, which caused apoptotic death in C6 cells prior to GdCl 3 exposure. GdCl 3 also caused an elevation in the cytoplasmic Ca 2+ level and reactive oxygen species (ROS) production, as well as the loss of mitochondrial membrane potential (ΔΨm) as shown by flow cytometric analysis in C6 cells. The results from the immunoblotting analysis demonstrated that there were upregulated protein levels of cytochrome c and Bax but a downregulated protein level of Bcl-2 in C6 cells after GdCl 3 treatment. Additionally, GdCl 3 decreased the protein levels of phosphorylated-extracellular signal-regulated kinases, phosphorylated-c-Jun N-terminal kinase and phosphorylated-p38 mitogen-activated protein kinases in C6 cells. In conclusion, ROS production and MAPKs signaling pathways contribute to GdCl 3-induced caspase cascade-mediated apoptosis in C6 cells. Our findings provide a better understanding of the molecular mechanisms underlying the role of GdCl 3 in rat glioma C6 cells.

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“…Documents reported that autophagy was wildly involved in variety of human diseases, such as cancer, inflammatory diseases, Parkinson disease, cardiovascular Disease, diabetes mellitus [42][43][44][45].…”

Section: Discussionmentioning

confidence: 99%

Rapamycin Alleviated the Symptoms of Fat Embolism Syndrome by Modulating Autophagy in a Rat Model

Zhang¹,

Zhang²,

Xu³

et al. 2017

Preprint

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As a high fatal disease, fat embolism syndrome is complication, which brought great pain to patient and their family served as a serious social burden. The mechanism of FES remains unclear. Autophagy controls the cell survival and homeostasis by removing the mis-folded proteins and damaged organelles as well as intracellular pathogens through a lysosomal degradation pathway. Increasing research documented that autophagy was wildly involved in variety of human diseases and had huge therapeutic potential. In our study, we first established the rat model of FES with the liquid fat by tail vein injection. We observed the up-regulated MPO expression and activity, increased Wet-to-Dry (W/D) lung weight, promoted quantity of fat granules, and the dominant disorder in the lung rat model of FES, compared to the control group. These observations demonstrated that we successfully build the rat model of FES. Then, we sought to dissect the role of the autophagy in the rat model of FES. The western blots analysis showed that the autophagy was inhibited in the rat model of FES constructed with liquid fat. Furthermore, Rapamycin could restore the repression of autophagy in rat model of FES. These investigations illustrated that autophagy was involved in FES. In addition, our experiments showed that Rapamycin could alleviate the symptoms of FES. Taken together, our study demonstrated the participation of autophagy in FES and further, as a potential therapeutic target, the modulation of autophagy could affect the symptom of rat model of FES.

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Autophagy and its link to type II diabetes mellitus

Cited by 88 publications

References 184 publications

Metformin‐induced autophagy and irisin improves INS‐1 cell function and survival in high‐glucose environment via AMPK/SIRT1/PGC‐1α signal pathway

Metformin‐induced autophagy and irisin improves INS‐1 cell function and survival in high‐glucose environment via AMPK/SIRT1/PGC‐1α signal pathway

Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells

Rapamycin Alleviated the Symptoms of Fat Embolism Syndrome by Modulating Autophagy in a Rat Model

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