Nicotinamide protects against diabetic kidney disease through regulation of Sirt1.

Abstract

PURPOSE:

To investigate the effect of nicotinamide (Nam) on diabetic kidney disease (DKD) in mice and explore its mechanism.

METHODS:

Thirty DBA/2 J mice were randomly assigned to three groups. After 8 weeks of hyperglycemia induced by streptozocin (STZ), Nam and saline were administrated to STZ + Nam and STZ + NS mice, respectively, for 8 weeks. Non-diabetic mice (NDM) were used as control group. Twenty In2-/- Akita mice were randomly divided into two groups. After 8 weeks of hyperglycemia, Nam and saline were administered to Akita + Nam and Akita + NS mice, respectively, for 6 weeks. Wild-type littermates were used as control group. Markers of renal injury were analyzed, and the molecular mechanisms were explored in human proximal tubular HK2 cells.

RESULTS:

Urinary albumin-to-creatinine ratio (UACR) and kidney injury molecule 1 (KIM-1) decreased in the STZ + Nam and Akita + Nam groups. Pathological analysis showed that Nam improved the structure of glomerular basement membrane, ameliorated glomerular sclerosis, and decreased the accumulation of extracellular matrix and collagen. Compared to the diabetic control group, renal fibrosis, inflammation, and oxidative stress were reduced in the Nam-treated mice. The expression of sirtuin 1 (Sirt1) in human proximal tubular HK2 cells was inhibited by high glucose and Nam treatment enhanced its expression. However, in HK2 cells with Sirt1 knockdown, the protective effect of Nam was abolished, indicating that the beneficial effect of Nam was partially dependent on Sirt1.

CONCLUSIONS:

Nam has a renoprotective effect against renal injury caused by hyperglycemia and may be a potential target for the treatment of DKD.

• Authors: Yeping Yang, Jinya Huang, Lijie Xie, Yilin Wang, Shizhe Guo, Meng Wang, Xiaoqing Shao, Wenjuan Liu, Yi Wang, Qin Li, Xia Wu, Zhaoyun Zhang, Fangfang Zeng, Wei Gong
• Journal: Endocrine (Endocrine) (Mar 06 2024) ISSN: 1559-0100 [Electronic] United States
• PMID: 38446387 (Publication Type: Journal Article)
• Copyright: © 2024. The Author(s).