Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway
Autor: | Xuemian Lu, Tinghao Liu, Yichun Jin, Yuanyuan Liu, Chi Zhang, Lechu Yu, Wenhan Wang |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Article Subject NF-E2-Related Factor 2 Endocrinology Diabetes and Metabolism chemistry.chemical_element Zinc Type 2 diabetes medicine.disease_cause Streptozocin Diseases of the endocrine glands. Clinical endocrinology Diabetes Mellitus Experimental Diabetes Complications 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Downregulation and upregulation Internal medicine medicine Metallothionein Animals Liver injury Chemistry Liver Diseases medicine.disease Streptozotocin Endoplasmic Reticulum Stress Lipid Metabolism RC648-665 Oxidative Stress 030104 developmental biology Diabetes Mellitus Type 2 030220 oncology & carcinogenesis Dietary Supplements Zinc deficiency Oxidative stress medicine.drug Research Article |
Zdroj: | Journal of Diabetes Research, Vol 2021 (2021) Journal of Diabetes Research |
ISSN: | 2314-6745 |
DOI: | 10.1155/2021/6662418 |
Popis: | Zinc is an essential trace element that is often reduced under the type 1 diabetic condition. Previous studies demonstrated that zinc deficiency enhanced type 1 diabetes-induced liver injury and that zinc supplementation significantly helped to prevent this. Due to the differences in pathogenesis between type 1 and type 2 diabetes, it is unknown whether zinc supplementation can induce a beneficial effect on type 2 diabetes-induced liver injury. This possible protective mechanism was investigated in the present study. A high-fat diet, along with a one-time dose of streptozotocin, was applied to metallothionein (MT) knockout mice, nuclear factor-erythroid 2-related factor (Nrf) 2 knockout mice, and age-matched wild-type (WT) control mice, in order to induce type 2 diabetes. This was followed by zinc treatment at 5 mg/kg body weight given every other day for 3 months. Global metabolic disorders of both glucose and lipids were unaffected by zinc supplementation. This induced preventive effects on conditions caused by type 2 diabetes like oxidative stress, apoptosis, the subsequent hepatic inflammatory response, fibrosis, hypertrophy, and hepatic dysfunction. Additionally, we also observed that type 2 diabetes reduced hepatic MT expression, while zinc supplementation induced hepatic MT expression. This is a crucial antioxidant. A mechanistic study showed that MT deficiency blocked zinc supplementation-induced hepatic protection under the condition of type 2 diabetes. This suggested that endogenous MT is involved in the hepatic protection of zinc supplementation in type 2 diabetic mice. Furthermore, zinc supplementation-induced hepatic MT increase was unobserved once Nrf2 was deficient, indicating that Nrf2 mediated the upregulation of hepatic MT in response to zinc supplementation. Results of this study indicated that zinc supplementation prevented type 2 diabetes-induced liver injury through the activation of the Nrf2-MT-mediated antioxidative pathway. |
Databáze: | OpenAIRE |
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