The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes

Eguchi, Natsuki; Vaziri, Nosratola D.; Dafoe, Donald C.; Ichii, Hirohito

doi:10.3390/ijms22041509

Cited by 184 publications

(132 citation statements)

References 145 publications

(190 reference statements)

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“…In addition, through generation of excess nitric oxide (NO), palmitate causes mitochondrial DNA damage-induced apoptosis in INS-1 cells [ 91 ]. Palmitate was also reported to trigger ROS production from diverse sources including the mitochondrial electron transport chain [ 92 ], peroxisomes [ 93 ], or due to NADPH oxidase activation [ 94 ]. A recent transcriptomic/proteomic profiling using INS-1E cells and isolated human islet data further suggested that palmitate may elicit an oxidative stress response in beta-cells [ 86 ].…”

Section: Molecular Mechanisms Involved In Beta-cell Apoptosismentioning

confidence: 99%

Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies

Costes

Bertrand

Ravier

2021

IJMS

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Type 2 diabetes (T2D) is characterized by chronic hyperglycemia secondary to the decline of functional beta-cells and is usually accompanied by a reduced sensitivity to insulin. Whereas altered beta-cell function plays a key role in T2D onset, a decreased beta-cell mass was also reported to contribute to the pathophysiology of this metabolic disease. The decreased beta-cell mass in T2D is, at least in part, attributed to beta-cell apoptosis that is triggered by diabetogenic situations such as amyloid deposits, lipotoxicity and glucotoxicity. In this review, we discussed the molecular mechanisms involved in pancreatic beta-cell apoptosis under such diabetes-prone situations. Finally, we considered the molecular signaling pathways recruited by glucagon-like peptide-1-based therapies to potentially protect beta-cells from death under diabetogenic situations.

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Section: Molecular Mechanisms Involved In Beta-cell Apoptosismentioning

confidence: 99%

Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies

Costes

Bertrand

Ravier

2021

IJMS

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“…It has been reported that palmitate stimulates inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and that the upregulation of these proteins causes mitochondrial dysfunction in beta cells [ 16 ]. Therefore, we evaluated the effect of AF-13 treatment on palmitate-stimulated inflammation.…”

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory Activity of AF-13, an Antioxidant Compound Isolated from the Polar Fraction of Allomyrina dichotoma Larva, in Palmitate-Induced INS-1 Cells

Kim

Park

Baek

et al. 2021

Life

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This study was conducted to evaluate the fractions isolated from Allomyrina dichotoma larva extract (ADLE) that exhibited anti-apoptotic and anti-inflammatory effects. A total of 13 fractions were eluted from ADLE by centrifugal chromatography (CPC), and the polar AF-13 fraction was selected, which exerted a relatively protective effect against fat-induced toxicity in INS-1 cells. AF-13 treatment of palmitate-treated INS-1 cells decreased the expression level of apoptosis-related proteins and DNA fragmentation. AF-13 also significantly inhibited the production of nitric oxide and reactive oxygen species and the triglyceride content induced by palmitate, and the effect was found to be similar to that with ADLE treatment. Palmitate upregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) through the activation of NF-κB p65; however, this effect was significantly attenuated by AF-13 treatment. In conclusion, AF-13 is one of the major components of ADLE responsible for anti-apoptotic and anti-inflammatory activities.

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“…Pancreatic β-cells uptake STZ via Glut2 receptors, resulting in increased oxidative stress due to NO release and ROS production [ 22 ]. Pancreatic β-cells are typically prone to oxidative stress because of their relatively low expression of antioxidant enzymes [ 23 ]. Indeed, our data showed that INS-1 cells treated with STZ exhibited a dramatic increase in ROS and antioxidant enzymes.…”

Section: Discussionmentioning

confidence: 99%

The Coffee Diterpene, Kahweol, Ameliorates Pancreatic β-Cell Function in Streptozotocin (STZ)-Treated Rat INS-1 Cells through NF-kB and p-AKT/Bcl-2 Pathways

et al. 2021

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Kahweol is a diterpene molecule found in coffee that exhibits a wide range of biological activity, including anti-inflammatory and anticancer properties. However, the impact of kahweol on pancreatic β-cells is not known. Herein, by using clonal rat INS-1 (832/13) cells, we performed several functional experiments including; cell viability, apoptosis analysis, insulin secretion and glucose uptake measurements, reactive oxygen species (ROS) production, as well as western blotting analysis to investigate the potential role of kahweol pre-treatment on damage induced by streptozotocin (STZ) treatment. INS-1 cells pre-incubated with different concentrations of kahweol (2.5 and 5 µM) for 24 h, then exposed to STZ (3 mmol/L) for 3 h reversed the STZ-induced effect on cell viability, apoptosis, insulin content, and secretion in addition to glucose uptake and ROS production. Furthermore, Western blot analysis showed that kahweol downregulated STZ-induced nuclear factor kappa B (NF-κB), and the antioxidant proteins, Heme Oxygenase-1 (HMOX-1), and Inhibitor of DNA binding and cell differentiation (Id) proteins (ID1, ID3) while upregulated protein expression of insulin (INS), p-AKT and B-cell lymphoma 2 (BCL-2). In conclusion, our study suggested that kahweol has anti-diabetic properties on pancreatic β-cells by suppressing STZ induced apoptosis, increasing insulin secretion and glucose uptake. Targeting NF-κB, p-AKT, and BCL-2 in addition to antioxidant proteins ID1, ID3, and HMOX-1 are possible implicated mechanisms.

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The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes

Cited by 184 publications

References 145 publications

Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies

Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies

Anti-Inflammatory Activity of AF-13, an Antioxidant Compound Isolated from the Polar Fraction of Allomyrina dichotoma Larva, in Palmitate-Induced INS-1 Cells

The Coffee Diterpene, Kahweol, Ameliorates Pancreatic β-Cell Function in Streptozotocin (STZ)-Treated Rat INS-1 Cells through NF-kB and p-AKT/Bcl-2 Pathways

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