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
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, b...
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doaj-54dfde67e3df45fbbe9ce7e9b3fe47252020-11-25T02:04:45ZengElsevierRedox Biology2213-23172016-10-019C22924310.1016/j.redox.2016.08.007The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studiesCatalina Carrasco-Pozo0Kah Ni Tan1Marjorie Reyes-Farias2Nicole De La Jara3Shyuan Thieu Ngo4Diego Fernando Garcia-Diaz5Paola Llanos6Maria Jose Cires7Karin Borges8Department of Nutrition, Faculty of Medicine, University of Chile, P.O. Box 8380453, Santiago, ChileSchool of Biomedical Sciences, The University of Queensland, Brisbane QLD 4072, AustraliaDepartment of Nutrition, Faculty of Medicine, University of Chile, P.O. Box 8380453, Santiago, ChileDepartment of Nutrition, Faculty of Medicine, University of Chile, P.O. Box 8380453, Santiago, ChileSchool of Biomedical Sciences, The University of Queensland, Brisbane QLD 4072, AustraliaDepartment of Nutrition, Faculty of Medicine, University of Chile, P.O. Box 8380453, Santiago, ChileInstitute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Santiago, ChileDepartment of Nutrition, Faculty of Medicine, University of Chile, P.O. Box 8380453, Santiago, ChileSchool of Biomedical Sciences, The University of Queensland, Brisbane QLD 4072, AustraliaStudying 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.http://www.sciencedirect.com/science/article/pii/S2213231716301215CholesterolGlycemic controlMitochondrial dysfunctionQuercetinSirtuin-1NFκB |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Catalina Carrasco-Pozo Kah Ni Tan Marjorie Reyes-Farias Nicole De La Jara Shyuan Thieu Ngo Diego Fernando Garcia-Diaz Paola Llanos Maria Jose Cires Karin Borges |
spellingShingle |
Catalina Carrasco-Pozo Kah Ni Tan Marjorie Reyes-Farias Nicole De La Jara Shyuan Thieu Ngo Diego Fernando Garcia-Diaz Paola Llanos Maria Jose Cires Karin Borges 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 Redox Biology Cholesterol Glycemic control Mitochondrial dysfunction Quercetin Sirtuin-1 NFκB |
author_facet |
Catalina Carrasco-Pozo Kah Ni Tan Marjorie Reyes-Farias Nicole De La Jara Shyuan Thieu Ngo Diego Fernando Garcia-Diaz Paola Llanos Maria Jose Cires Karin Borges |
author_sort |
Catalina Carrasco-Pozo |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2016-10-01 |
description |
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. |
topic |
Cholesterol Glycemic control Mitochondrial dysfunction Quercetin Sirtuin-1 NFκB |
url |
http://www.sciencedirect.com/science/article/pii/S2213231716301215 |
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