Pancreas protective effects of Urolithin A on type 2 diabetic mice induced by high fat and streptozotocin via regulating autophagy and AKT/mTOR signaling pathway
| Autor: | Xinmin Mao, Bahetibieke Tuohetaerbaike, Yanzhi Zhang, Xuejun Li, Yan Zhang, Yali Tian, Jin-sen Kang, Nan nan Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Diet High-Fat Streptozocin Diabetes Mellitus Experimental 03 medical and health sciences Mice 0302 clinical medicine Sequestosome 1 Downregulation and upregulation Coumarins Internal medicine Diabetes mellitus Drug Discovery medicine Autophagy Animals education Protein kinase B Pancreas PI3K/AKT/mTOR pathway 030304 developmental biology Pharmacology 0303 health sciences education.field_of_study Chemistry TOR Serine-Threonine Kinases Chloroquine Streptozotocin medicine.disease Urolithin Mice Inbred C57BL Endocrinology Diabetes Mellitus Type 2 030220 oncology & carcinogenesis Proto-Oncogene Proteins c-akt medicine.drug Signal Transduction |
| Zdroj: | Journal of ethnopharmacology. 250 |
| ISSN: | 1872-7573 |
| Popis: | Ethnopharmacological relevance Urolithin A (UroA), the main intestinal microflora metabolite of ellagic acid of berries, pomegranate,and some other traditional chinese herbals such as emblica officinalis,etc,has been reported to exhibit anti-inflammatory, anti-oxidative, anti-tumor and pro-autophagy effects. Aim of the study This study evaluated the anti-diabetic and pancreas-protective effects of UroA using a mice model of type 2 diabetes and preliminarily explored its effect on autophagy as well as the mechanism involved. Materials and methods Type 2 diabetes model was induced by high-fat diet (HFD; 60% energy as fat) and low-dose streptozotocin (85 mg/kg) injection. Mice were administered with UroA (50 mg/kg/d) alone or UroA-chloroquine (autophagy inhibitor) combination for 8 weeks. Results UroA improved symptoms of diabetic mice such as high water intake volume, high urine volume, significantly decreased fasting blood glucose (FBG), after-glucose-loading glucose, glycated hemoglobin (GHb) levels, plasma C-peptide, malondialdehyde (MDA) and interleukin-1 β level, increased reduced glutathione (GSH), interleukin-10 content, and glucose tolerance. UroA also improved pancreatic function indexes such as HOMA-β as evidenced by improved pathological and ultrastructural features of the pancreas assessed by light microscopy and transmission electron microscopy (TEM). Accordingly, UroA decreased mitochondrial swelling and myelin-like cytoplasmic inclusions. UroA significantly upregulated the protein levels of microtubule-associated protein 1 light chain 3-II (LC3II) and beclin1, downregulated sequestosome 1 (p62) accompanied by decreased expression of apoptotic protein cleaved caspase3 in pancreas of diabetic mice. In addition, it increased the phosphorylation level of protein kinase B (p-Akt) and mammalian target of rapamycin (p-mTOR). Most of these effects of UroA were reversed by treatment with autophagy inhibitor chloroquine. Conclusions Our findings reveal that the pancreas protective effects of UroA against diabetes were partially mediated by its regulation of autophagy and AKT/mTOR signal pathway. |
| Databáze: | OpenAIRE |
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