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Nicotinamide protects against diabetic kidney disease through regulation of Sirt1
Yeping Yang1, Jinya Huang1, Lijie Xie1
1Division of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, 200040, China.
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.
Insights
Nicotinamide (Nam) shows a renoprotective effect against diabetic kidney disease (DKD) in mice. This vitamin B3 derivative may be a potential therapeutic target for DKD treatment by enhancing sirtuin 1 (Sirt1) expression.
Area of Science:
- Biochemistry
- Nephrology
- Pharmacology
Background:
- Diabetic kidney disease (DKD) is a major complication of diabetes mellitus.
- Existing treatments for DKD have limited efficacy and significant side effects.
- Exploring novel therapeutic agents like nicotinamide (Nam) is crucial for DKD management.
Purpose of the Study:
- To investigate the renoprotective effects of nicotinamide (Nam) in mouse models of diabetic kidney disease (DKD).
- To elucidate the underlying molecular mechanisms of Nam's action in DKD.
Main Methods:
- Two mouse models of DKD were established using streptozotocin (STZ) and Akita mice.
- Mice received nicotinamide (Nam) or saline treatment for 6-8 weeks.
- Renal injury markers, kidney structure, and molecular pathways (including Sirt1 expression) were analyzed in vivo and in vitro using HK2 cells.
Main Results:
- Nicotinamide (Nam) treatment significantly reduced urinary albumin-to-creatinine ratio (UACR) and kidney injury molecule 1 (KIM-1) levels.
- Pathological analysis revealed improved glomerular basement membrane structure, reduced glomerular sclerosis, and decreased extracellular matrix accumulation in Nam-treated mice.
- Nam treatment inhibited renal fibrosis, inflammation, and oxidative stress, partly mediated by enhancing sirtuin 1 (Sirt1) expression.
Conclusions:
- Nicotinamide (Nam) demonstrates significant renoprotective effects against hyperglycemia-induced kidney injury.
- The beneficial effects of Nam in DKD are partially dependent on the activation of sirtuin 1 (Sirt1).
- Nam represents a promising therapeutic candidate for the treatment of diabetic kidney disease (DKD).
