Psoralea corylifoliaL. Seed Extract Ameliorates Streptozotocin-Induced Diabetes in Mice by Inhibition of Oxidative Stress

Pancreatic beta-cell death is known to be the cause of deficient insulin production in diabetes mellitus. Oxidative stress is one of the major causes of beta-cell death. In this study, we investigated the effects ofPsoralea corylifoliaL. seed (PCS) extract on beta-cell death. Oral administration of PCS extract resulted in a significant improvement of hyperglycemia in streptozotocin-induced diabetic mice. PCS extract treatment improved glucose tolerance and increased serum insulin levels. To study the mechanisms involved, we investigated the effects of PCS extract on H2O2-induced apoptosis in INS-1 cells. Treatment with PCS extract inhibited cell death. PCS extract treatment decreased reactive oxygen species level and activated antioxidative enzymes. Among the major components of PCS extract, psoralen and isopsoralen (coumarins), but not bakuchiol, showed preventive effects against H2O2-induced beta-cell death. These findings indicate that PCS extract may be a potential pharmacological agent to protect against pancreatic beta-cell damage caused by oxidative stress associated with diabetes.

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Prevention of Oxidative Stress-Induced Pancreatic Beta Cell Damage by Broussonetia kazinoki Siebold Fruit Extract via the ERK-Nox4 Pathway

Antioxidants ◽

10.3390/antiox9050406 ◽

2020 ◽

Vol 9 (5) ◽

pp. 406 ◽

Cited By ~ 1

Author(s):

Hyo-Jin Kim ◽

Donghee Kim ◽

Haelim Yoon ◽

Cheol Soo Choi ◽

Yoon Sin Oh ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Cell Damage ◽

Beta Cell Death ◽

Min6 Cells ◽

Erk Phosphorylation ◽

Beta Cell Damage

Pancreatic beta cells are vulnerable to oxidative stress, which causes beta cell death and dysfunction in diabetes mellitus. Broussonetia kazinoki Siebold (BK) is a widely used herbal medicine, but its potential effects against beta cell death-induced diabetes have not been studied. Therefore, we investigated the protective effect of an ethanolic extract of BK fruit (BKFE) against streptozotocin (STZ)-induced toxicity in pancreatic beta cells. Intraperitoneal injection of STZ in mice induced hyperglycemia; however, oral administration of BKFE significantly decreased the blood glucose level as well as HbA1c levels. BKFE treatment improved glucose tolerance and increased body weight in diabetic mice. Moreover, BKFE treatment resulted in increased serum insulin levels and insulin expression in the pancreas as well as decreased 4-hydroxynonenal levels induced by oxidative stress. Treatment with STZ decreased cell viability of mouse insulinoma cells (MIN6), which was blocked by BKFE pretreatment. BKFE significantly inhibited apoptotic cells and decreased the expression levels of cleaved-caspase-3 and cleaved-poly (ADP-ribose) polymerase (PARP) induced by STZ treatment. Production of reactive oxygen species in STZ-treated MIN6 cells was also significantly decreased by treatment with BKFE. Erk phosphorylation and Nox4 levels increased in STZ-treated MIN6 cells and the pancreas of mice injected with STZ and this increase was inhibited by treatment with BKFE. Inhibition of Erk phosphorylation by treatment with the PD98059 inhibitor or siRNA Erk also blocked the expression of Nox4 induced by STZ treatment. In conclusion, BKFE inhibits Erk phosphorylation, which in turn prevents STZ-induced oxidative stress and beta cell apoptosis. These results suggested that BKFE can be used to prevent or treat beta cell damage in diabetes.

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EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2016.12.005 ◽

2017 ◽

Vol 315 ◽

pp. 60-69 ◽

Cited By ~ 20

Author(s):

Mi-Hwi Kim ◽

Eung-Hwi Kim ◽

Hye Seung Jung ◽

Dongki Yang ◽

Eun-Young Park ◽

...

Keyword(s):

Oxidative Stress ◽

Beta Cell ◽

Cell Damage ◽

Pancreatic Beta Cell ◽

Beta Cell Damage

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Perinatal exposure to silver nanoparticles reprograms immunometabolism and promotes pancreatic beta-cell death and kidney damage in mice

Nanotoxicology ◽

10.1080/17435390.2021.1909767 ◽

2021 ◽

pp. 1-25

Author(s):

Ratnakar Tiwari ◽

Radha Dutt Singh ◽

Monika Binwal ◽

Anurag Kumar Srivastav ◽

Neha Singh ◽

...

Keyword(s):

Silver Nanoparticles ◽

Cell Death ◽

Beta Cell ◽

Pancreatic Beta Cell ◽

Kidney Damage ◽

Perinatal Exposure ◽

Beta Cell Death

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Nitric oxide and neuronal and pancreatic beta cell death

Toxicology ◽

10.1016/s0300-483x(00)00310-3 ◽

2000 ◽

Vol 153 (1-3) ◽

pp. 143-156 ◽

Cited By ~ 20

Author(s):

E Adeghate ◽

S.H Parvez

Keyword(s):

Nitric Oxide ◽

Cell Death ◽

Beta Cell ◽

Pancreatic Beta Cell ◽

Beta Cell Death

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APPL1 prevents pancreatic beta cell death and inflammation by dampening NFκB activation in a mouse model of type 1 diabetes

Diabetologia ◽

10.1007/s00125-016-4185-z ◽

2016 ◽

Vol 60 (3) ◽

pp. 464-474 ◽

Cited By ~ 7

Author(s):

Xue Jiang ◽

Yawen Zhou ◽

Kelvin K. L. Wu ◽

Zhanrui Chen ◽

Aimin Xu ◽

...

Keyword(s):

Cell Death ◽

Type 1 Diabetes ◽

Mouse Model ◽

Beta Cell ◽

Pancreatic Beta Cell ◽

Beta Cell Death

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The adaptor protein NumbL is involved in the control of glucolipotoxicity-induced pancreatic beta cell apoptosis

10.1101/2020.08.16.253286 ◽

2020 ◽

Author(s):

Halesha D. Basavarajappa ◽

Jose M. Irimia ◽

Patrick T. Fueger

Keyword(s):

Cell Death ◽

Beta Cell ◽

Beta Cells ◽

Cell Apoptosis ◽

Molecular Mechanisms ◽

Pancreatic Beta Cell ◽

Adaptor Protein ◽

Beta Cell Apoptosis ◽

Beta Cell Death ◽

Egf Signaling

AbstractAvoiding loss of functional beta cell mass is critical for preventing or treating diabetes. Currently, the molecular mechanisms underlying beta cell death are partially understood, and there is a need to identify new targets for developing novel therapeutics to treat diabetes. Previously, our group established that Mig6, an inhibitor of EGF signaling, mediates beta cell death under diabetogenic conditions. The objective of this study was to clarify the mechanisms linking diabetogenic stimuli to beta cell death by investigating Mig6-interacting proteins. Using co-immunoprecipitation and mass spectrometry, we evaluated the binding partners of Mig6 under both normal glucose (NG) and glucolipotoxic (GLT) conditions in beta cells. We identified that Mig6 interacts dynamically with NumbL; whereas Mig6 associates with NumbL under NG, this interaction is disrupted under GLT conditions. Further, we demonstrate that siRNA-mediated suppression of NumbL expression in beta cells prevented apoptosis under GLT conditions by blocking activation of NF-κB signaling. Using co-immunoprecipitation experiments we observed that NumbL’s interactions with TRAF6, a key component of NFκB signaling, are increased under GLT conditions. The interactions among Mig6, NumbL, and TRAF6 are dynamic and context-dependent. We propose a model wherein these interactions activate pro-apoptotic NF-κB signaling while blocking pro-survival EGF signaling under diabetogenic conditions, leading to beta cell apoptosis. These findings indicate that NumbL should be further investigated as a candidate anti-diabetic therapeutic target.

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