Mechanistic insights into the effects of quercetin and/or GLP-1 analogue liraglutide on high-fat diet/streptozotocin-induced type 2 diabetes in rats

Gaballah, Hanaa Hibishy; Zakaria, Soha S.; Mwafy, Shorouk E.; Tahoon, Nahid; Ebeid, Abla M.

doi:10.1016/j.biopha.2017.05.086

Cited by 45 publications

(29 citation statements)

References 57 publications

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“…6A,B, the diabetic mice had significantly elevated blood glucose levels, whereas their blood insulin levels were significantly decreased compared with the normal control group, which are consistent with previous report [24]. Therefore, DP may be a potential therapy for diabetes by promoting Pdx1 expression and preventing b-cell apoptosis.…”

Section: Dp Improves Hyperglycemia In T2dm Micesupporting

confidence: 89%

Dracorhodin perchlorate protects pancreatic β‐cells against glucotoxicity‐ or lipotoxicity‐induced dysfunction and apoptosis in vitro and in vivo

et al. 2019

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Glucotoxicity or lipotoxicity leads to hyperglycemia and insulin secretion deficiency, which are important causes for the onset of type 2 diabetes mellitus (T2DM). Thus, the restoration of β‐cell function is a long‐sought goal in diabetes research. Previous studies have implicated pancreatic and duodenal homeobox 1 gene (Pdx1) in β‐cell function and insulin secretion. In this study, we established a Pdx1 promoter‐dependent luciferase system and identified the natural compound dracorhodin perchlorate (DP) as an effective promotor of Pdx1 expression. We further demonstrated that DP could significantly inhibit β‐cell apoptosis induced by 33 mm glucose or 200 μm palmitate by interfering with endoplasmic reticulum stress and mitochondrial pathways and enhance insulin secretion as well. These effects were associated with enhanced activities of Erk1/2, which in turn promoted Pdx1 expression and increased the ratio of Bcl2/Bax, since inhibition of the Erk1/2 pathway abolished the DP‐induced expression of Pdx1 and suppression of apoptosis. In addition, our in vivo results in diabetic mice indicated that DP treatment lowered blood glucose, raised insulin levels, enhanced Pdx1 expression and increased islet size and number in the pancreas of diabetic mice. Our findings suggest that Pdx1 is a potential target molecule of DP in the treatment of T2DM via the inhibition of glucotoxicity‐ or lipotoxicity‐ induced β‐cell apoptosis and the attenuation of insulin secretion dysfunction.

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Section: Dp Improves Hyperglycemia In T2dm Micesupporting

confidence: 89%

Dracorhodin perchlorate protects pancreatic β‐cells against glucotoxicity‐ or lipotoxicity‐induced dysfunction and apoptosis in vitro and in vivo

et al. 2019

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“…In addition to antitumor, antiobesity, antihypertensive, and significant heart‐related benefits, a large number of in vivo studies have shown that quercetin had a strong potential for antidiabetes and its complications (Bule, Abdurahman, Nikfar, Abdollahi, & Amini, ; Hu et al, ; Lu et al, ; Marunaka et al, ; Patel et al, ; Shi et al, ; Y. Zhao et al, ; X. Zhu, Cheng, et al, ; Y. Zhu, Teng, et al, ). It has been found that quercetin prevents diabetes mellitus by decreasing blood glucose via enhancing insulin sensitivity and stimulating insulin secretion from β cells (Gaballah, Zakaria, Mwafy, Tahoon, & Ebeid, ; Jeong, Kang, Choi, Kim, & Kim, ). In addition, our previous researches had shown that quercetin could effectively improve diabetic complications (such as diabetic nephropathy, diabetic encephalopathy, and diabetic cataract) mainly by ameliorating inflammation and improving antioxidant capacity (Du et al, ; Y. W. Liu, Liu, et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Zhu, Teng, et al, 2018). It has been found that quercetin prevents diabetes mellitus by decreasing blood glucose via enhancing insulin sensitivity and stimulating insulin secretion from β cells (Gaballah, Zakaria, Mwafy, Tahoon, & Ebeid, 2017;Jeong, Kang, Choi, Kim, & Kim, 2012). In addition, our previous researches had shown that quercetin could effectively improve diabetic complications (such as diabetic nephropathy, diabetic encephalopathy, and diabetic cataract) mainly by ameliorating inflammation and improving antioxidant capacity Y.…”

mentioning

confidence: 99%

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Yang

Cai

et al. 2019

Phytotherapy Research

167

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Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM‐induced NAFLD were investigated. T2DM‐induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM‐induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM‐induced production of interleukin 1 beta, interleukin 6, and TNF‐α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM‐induced NAFLD. In high D‐glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM‐induced NAFLD.

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“…Blood was collected into a dry sterile centrifuge tube, allowed to clot at room temperature for 30 minutes, and then centrifuged at 1000 g for 20 minutes at 4°C; serum was separated and stored at −80°C until the time of analysis …”

Section: Methodsmentioning

confidence: 99%

Hesperidin promotes lysosomal biogenesis in chronically ethanol‐induced cardiotoxicity in rats: A proposed mechanisms of protection

Gaballah

Ghanem

Tahoon

et al. 2018

J Biochem & Molecular Tox

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Alcohol consumption is a major global risk factor for mortality and morbidity. We aimed to delineate the mechanisms underlying the potential ameliorative effects of hesperidin against chronically ethanol‐induced cardiotoxicity. Sixty male albino rats were divided into normal control group, hesperidin‐treated control group, untreated alcoholic group, and hesperidin‐treated alcoholic group. Transcription factor‐EB (TFEB) expression levels were estimated using real‐time reverse transcription‐polymerase chain reaction. Peroxisome proliferator–activated receptor γ coactivator 1‐α (PGC1‐α), macrophage inflammatory protein‐1 α, poly‐(ADP‐ribose)‐polymerase‐1 (PARP‐1) activity, and tenascin C levels in cardiac tissues were estimated by enzyme‐linked immunosorbent assay; while tissue malondialdehyde and total antioxidant capacity were evaluated spectrophotometrically. Our data portrayed promoting lysosomal biogenesis, as judged by upregulation of TFEB expression and its target PGC1‐α, as well as decreased PARP‐1 activity and offsetting inflammation, oxidative stress, and tissue injury as the principal culprits mediating the cardioprotective effect of hesperidin in alcohol‐induced cardiotoxicity. In conclusion, hesperidin can be used as a cardioprotective agent in chronically ethanol‐induced cardiotoxicity.

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Mechanistic insights into the effects of quercetin and/or GLP-1 analogue liraglutide on high-fat diet/streptozotocin-induced type 2 diabetes in rats

Cited by 45 publications

References 57 publications

Dracorhodin perchlorate protects pancreatic β‐cells against glucotoxicity‐ or lipotoxicity‐induced dysfunction and apoptosis in vitro and in vivo

Dracorhodin perchlorate protects pancreatic β‐cells against glucotoxicity‐ or lipotoxicity‐induced dysfunction and apoptosis in vitro and in vivo

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Hesperidin promotes lysosomal biogenesis in chronically ethanol‐induced cardiotoxicity in rats: A proposed mechanisms of protection

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