Flavonoids protect pancreatic beta-cells from cytokines mediated apoptosis through the activation of PI3-kinase pathway

Lin, Chia-Yu; Ni, C; Yin, Mei‐chin; Lii, Chong‐Kuei

doi:10.1016/j.cyto.2012.04.011

Cited by 51 publications

(27 citation statements)

References 36 publications

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“…7) and increased the expression of several NFκB-regulated cytokines (Table 1) indicates that NFκB activation underlies cholesterol-induced β-cell GSIS dysfunction and glycemic control impairment. The decrease in GSIS and the increase in oxidative stress and mitochondrial dysfunction in INS-1 and RINm5F pancreatic β-cells in the presence of combined cytokines: IL-1β, TNF-α and IFN-γ [20], [23] suggest that cytokines exert synergic detrimental effects on insulin-secreting cells. The antioxidant properties of QUE may also contribute to the prevention of cholesterol-induced NFκB pathway activation observed in this study, since ROS are associated with NFκB activation through the increase in I-κB degradation [61].…”

Section: Discussionmentioning

confidence: 99%

“…Cytokine-induced mitochondrial dysfunction through activation of the NFκB-pathway and oxidative stress may also trigger β-cell death [20], [21], [22], [23]. Quercetin has been shown to prevent cytokine-induced pancreatic β-cell death by counteracting the mitochondrial apoptosis pathway and NFκB signalling, thereby preserving glucose-stimulated insulin secretion (GSIS) [20], [21], [22], [23]. In addition, QUE via the ERK1/2 pathway, protects β-cells against oxidative damage [24].…”

Section: Introductionmentioning

confidence: 99%

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The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studies

et al. 2016

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Studying rats fed high cholesterol diet and a pancreatic β-cell line (Min6), we aimed to determine the mechanisms by which quercetin protects against cholesterol-induced pancreatic β-cell dysfunction and impairments in glycemic control. Quercetin prevented the increase in total plasma cholesterol, but only partially prevented the high cholesterol diet-induced alterations in lipid profile. Quercetin prevented cholesterol-induced decreases in pancreatic ATP levels and mitochondrial bioenergetic dysfunction in Min6 cells, including decreases in mitochondrial membrane potentials and coupling efficiency in the mitochondrial respiration (basal and maximal oxygen consumption rate (OCR), ATP-linked OCR and reserve capacity). Quercetin protected against cholesterol-induced apoptosis of Min6 cells by inhibiting caspase-3 and -9 activation and cytochrome c release. Quercetin prevented the cholesterol-induced decrease in antioxidant defence enzymes from pancreas (cytosolic and mitochondrial homogenates) and Min6 cells and the cholesterol-induced increase of cellular and mitochondrial oxidative status and lipid peroxidation. Quercetin counteracted the cholesterol-induced activation of the NFκB pathway in the pancreas and Min6 cells, normalizing the expression of pro-inflammatory cytokines. Quercetin inhibited the cholesterol-induced decrease in sirtuin 1 expression in the pancreas and pancreatic β-cells. Taken together, the anti-apoptotic, antioxidant and anti-inflammatory properties of quercetin, and its ability to protect and improve mitochondrial bioenergetic function are likely to contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction, thereby preserving glucose-stimulated insulin secretion (GSIS) and glycemic control. Specifically, the improvement of ATP-linked OCR and the reserve capacity are important mechanisms for protection of quercetin. In addition, the inhibition of the NFκB pathway is an important mechanism for the protection of quercetin against cytokine mediated cholesterol-induced glycemic control impairment. In summary, our data highlight cellular, molecular and bioenergetic mechanisms underlying quercetin's protective effects on β-cells in vitro and in vivo, and provide a scientifically tested foundation upon which quercetin can be developed as a nutraceutical to preserve β-cell function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studies

et al. 2016

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“…Recently it has been demonstrated that quercetin, quercitrin are potential candidates to prevent β-cell death via the mitochondrial pathway and NF-κB signaling, and quercetin may be more efficacious than quercitrin as an antidiabetic agent [104]. Similarly, myricetin protects against cytokine-induced cell death in RIN-m5f β cells [105], and naringenin inhibit cytokine-induced toxicity in β-cells by enhancing cell survival through PI3-kinase pathway, independent of p-p38 MAPK or iNOS [106]. According to these, under the OLEA projects we found that olive leaf polyphenolic mixture or olive leaf polyphenols, which are the special interest of our laboratory, had cytoprotective and anti-inflammatory effects tested in insulin releasing β-cell by H2O 2 , 4-hydroxynonenal (4-HNE) or a cytokine cocktail [56,57,89,90].…”

Section: The Natural Regulators Of Cellular Redox Homeostasis and Promentioning

confidence: 95%

Natural products and the aging process

Ergin

Bali²,

Hariry

et al. 2013

Hormone Molecular Biology and Clinical Investigation

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Literature surveys show that the most of the research that have been conducted on the effect of herbal remedies on many tissue pathologies, including metabolic disturbances, cardiovascular decline, neurodegeneration, cataract, diabetic retinopathy and skin inflammation, all lead to an accelerated aging process. The increased carbonylation of proteins (carbonyl stress) disturbing their function has been indicated as an underlying mechanism of cellular senescence and age-related diseases. Because it is also linked to the carbonyl stress, aging chronic disease and inflammation plays an important role in understanding the clinical implications of cellular stress response and relevant markers. Greater knowledge of the molecular and cellular mechanisms involved in several pathologies associated with aging would provide a better understanding to help us to develop suitable strategies, use specific targets to mitigate the effect of human aging, prevent particularly chronic degenerative diseases and improve quality of life. However, research is lacking on the herbal compounds affecting cellular aging signaling as well as studies regarding the action mechanism(s) of natural products in prevention of the age-related disease. This review provides leads for identifying new medicinal agents or potential phytochemical drugs from plant sources for the prevention or delaying cellular aging processes and the treatment of some disorders related with accelerated body aging.

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“…[4] The complex, fluorescent AGE molecules formed during Maillard reaction can lead to protein cross-linking, which contributes to the development and progression of various diabetic complications. [5] Many researchers have discussed the pathological features of diabetes, that are caused to a great extent by the accelerated formation of AGEs promoted by hyperglycaemia in tissues. [6] Inhibition of the formation of AGEs has been shown to be an effective way of retarding the full range of diabetes complications, such as nephropathy, neuropathy, retinopathy and vasculopathy.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of antidiabetic, antioxidant and antiglycating activities of the Eysenhardtia polystachya

Gutierrez

Baez²

2014

Phcog Mag

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Background:Many diseases are associated with oxidative stress caused by free radicals. The aim of the present study was to evaluate the antidiabetic, antioxidant and antiglycation properties of Eysenhardtia polystachya (EP) bark methanol-water extract.Materials and Methods: The antioxidant capacities were evaluated by studying in vitro the scavenging of DPPH and ABTS free radical, reactive oxygen species such as RO2, O2·-, H2O2, OH., H2O2, ONOO-, NO, HOCl,1 O2, chelating ability, ORAC, β-carotene-bleaching and lipid peroxidation. The antiglycation activities of EP were evaluated by haemoglobin, bovine serum albumin (BSA)-glucose, BSA-methylglyoxal and BSA-glucose assays. Oral administration of EP at the doses of 100 mg/kg, 200 mg/kg and 400 mg/g was studied in normal, glucose-loaded and antidiabetic effects on streptozotocin-induced mildly diabetic (MD) and severely diabetic (SD) mice.Results:EP showed Hdonor activity, free radical scavenging activity, metal chelating ability and lipid peroxidation Antioxidant activity may be attributed to the presence of phenolic and flavonoid compounds. EP is an inhibitor of fluorescent AGE, methylglyoxal and the glycation of haemoglobin. In STZ-induced diabetic mice, EP reduced the blood glucose, increased serum insulin, body weight, marker enzymes of hepatic function, glycogen, HDL, GK and HK while there was reduction in the levels of triglyceride, cholesterol, TBARS, LDL and G6Pase.Conclusions:Eysenhardtia polystachya possesses considerable antioxidant activity with reactive oxygen species (ROS) scavenging activity and demonstrated an anti-AGEs and hepatoprotective role, inhibits hyperglycemic, hyperlipidemic and oxidative stress indicating that these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.

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Flavonoids protect pancreatic beta-cells from cytokines mediated apoptosis through the activation of PI3-kinase pathway

Cited by 51 publications

References 36 publications

The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studies

The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studies

Natural products and the aging process

Evaluation of antidiabetic, antioxidant and antiglycating activities of the Eysenhardtia polystachya

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