Microdose Lithium Protects against Pancreatic Islet Destruction and Renal Impairment in Streptozotocin-Elicited Diabetes

Zhang, Jiahui and Anshul, Fnu and Malhotra, Deepak K. and Jaume, Juan and Dworkin, Lance D. and Gong, Rujun (2021) Microdose Lithium Protects against Pancreatic Islet Destruction and Renal Impairment in Streptozotocin-Elicited Diabetes. Antioxidants, 10 (1). p. 138. ISSN 2076-3921

[thumbnail of antioxidants-10-00138-v3.pdf] Text
antioxidants-10-00138-v3.pdf - Published Version

Download (3MB)

Abstract

Psychiatric use of lithium has been associated with hypoglycemic effects, but its effect on type 1 diabetes mellitus (T1D) is unknown. In streptozotocin (STZ) induced murine models of T1D, microdose lithium therapy improved hyperglycemia, attenuated body weight loss and prevented early signs of diabetic kidney injury. This beneficial effect was associated with preservation of pancreatic islet histology and β-cell production of insulin as well as mitigated oxidative damage of islets. Mechanistically, lithium in islets cells induced inhibitory phosphorylation of glycogen synthase kinase 3β (GSK3β), the major molecular target of lithium that has been recently implicated in non-canonical regulation of Nrf2 activity. In turn, Nrf2 antioxidant response was potentiated in islets, marked by nuclear translocation of Nrf2 and augmented expression of its target antioxidant enzyme heme oxygenase 1 (HO-1). Conversely, cotreatment with trigonelline, a selective blockade of Nrf2, offset the lithium enhanced Nrf2 antioxidant response in islets, blunted the protective effect of lithium on pancreatic islets and β-cells, and abolished the hypoglycemic activity of lithium in STZ-injured mice. Collectively, our findings suggest that microdose lithium confers a protective effect on islet β-cells via targeting the GSK3β-regulated Nrf2 antioxidant response and thereby ameliorates T1D and its related kidney impairment.

Item Type: Article
Subjects: Afro Asian Library > Agricultural and Food Science
Depositing User: Unnamed user with email support@afroasianlibrary.com
Date Deposited: 01 Jul 2023 09:38
Last Modified: 12 Sep 2024 04:44
URI: http://classical.academiceprints.com/id/eprint/1201

Actions (login required)

View Item
View Item