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
| Autor: | Nicole de la Jara, Karin Borges, Paola Llanos, Marjorie Reyes-Farias, Kah Ni Tan, Shyuan T. Ngo, Diego F. Garcia-Diaz, Catalina Carrasco-Pozo, Maria Jose Cires |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine Sirtuin-1 Clinical Biochemistry Apoptosis Biochemistry Antioxidants Lipid peroxidation chemistry.chemical_compound Glycemic control Insulin-Secreting Cells Insulin heterocyclic compounds Inner mitochondrial membrane lcsh:QH301-705.5 lcsh:R5-920 Organelle Biogenesis biology NF-kappa B Mitochondria 3. Good health Cholesterol medicine.anatomical_structure Cytokines Quercetin Inflammation Mediators medicine.symptom lcsh:Medicine (General) Pancreas Oxidation-Reduction Research Paper medicine.medical_specialty Cell Survival Inflammation Oxidative phosphorylation Cell Line 03 medical and health sciences Internal medicine medicine Animals Sirtuin 1 Organic Chemistry Rats Oxidative Stress 030104 developmental biology Endocrinology lcsh:Biology (General) Gene Expression Regulation chemistry biology.protein Mitochondrial dysfunction NFκB |
| Zdroj: | Redox Biology Redox Biology, Vol 9, Iss C, Pp 229-243 (2016) |
| ISSN: | 2213-2317 |
| DOI: | 10.1016/j.redox.2016.08.007 |
| Popis: | 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. Graphical abstract fx1 Highlights • Quercetin prevents the impairment in glycemic control induced by cholesterol. • Quercetin prevents cholesterol-impaired insulin secretion in pancreatic β-cells. • Quercetin improves mitochondrial bioenergetics impaired by cholesterol. • Quercetin prevents the decrease in SIRT1 expression induced by cholesterol. • Quercetin prevents NF-kB activation and prevents cholesterol-induced inflammation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|