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

Carrasco-Pozo, Catalina, Tan, Kah Ni, Reyes-Farias, Marjorie, De La Jara, Nicole, Ngo, Shyuan Thieu, Garcia-Diaz, Diego Fernando, Llanos, Paola, Cires, Maria Jose and Borges, Karin (2016) 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, 9 229-243. doi:10.1016/j.redox.2016.08.007


Author Carrasco-Pozo, Catalina
Tan, Kah Ni
Reyes-Farias, Marjorie
De La Jara, Nicole
Ngo, Shyuan Thieu
Garcia-Diaz, Diego Fernando
Llanos, Paola
Cires, Maria Jose
Borges, Karin
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
Journal name Redox Biology   Check publisher's open access policy
ISSN 2213-2317
Publication date 2016-10-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.redox.2016.08.007
Open Access Status DOI
Volume 9
Start page 229
End page 243
Total pages 15
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2017
Language eng
Abstract 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.
Keyword Cholesterol
Glycemic control
Mitochondrial dysfunction
Quercetin
Sirtuin-1
NFκB
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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