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Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination
Taisuke Ono1, Shingo Takada1, Shintaro Kinugawa1
1Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
New Findings:
What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1β and oxidative stress were increased in the skeletal muscle from DM mice and inhibited in DM+Curcumin mice. Curcumin ameliorated skeletal muscle atrophy in DM mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 DM.
Insights
Curcumin effectively combats skeletal muscle atrophy in diabetic mice by reducing protein ubiquitination, inflammation, and oxidative stress. This natural compound shows promise for treating muscle wasting in type 1 diabetes mellitus.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Skeletal muscle atrophy is a complication of diabetes mellitus (DM), particularly type 1 DM, linked to chronic inflammation.
- Curcumin, derived from turmeric, possesses anti-inflammatory and antioxidant properties.
- The study investigates curcumin's potential to mitigate muscle atrophy in a type 1 DM mouse model.
Purpose of the Study:
- To determine if curcumin can ameliorate skeletal muscle atrophy in diabetic mice.
- To investigate the mechanisms, including protein ubiquitination, inflammation, and oxidative stress, by which curcumin may exert its effects.
Main Methods:
- Streptozotocin was used to induce type 1 diabetes mellitus in C57BL/6 J mice.
- Mice were treated with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks.
- Body weight, muscle weight, cellular cross-sectional area, protein ubiquitination, inflammatory markers, and oxidative stress were assessed.
Main Results:
- Curcumin treatment attenuated decreases in body weight, muscle weight, and skeletal muscle cross-sectional area in diabetic mice.
- Curcumin reduced protein ubiquitination and the expression of atrogin-1/MAFbx and MuRF1.
- Curcumin inhibited nuclear factor-κB activation, inflammatory cytokines (TNF-α, IL-1β), and oxidative stress without altering glucose or insulin levels.
Conclusions:
- Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice.
- The beneficial effects are attributed to the inhibition of protein ubiquitination, inflammation, and oxidative stress.
- Curcumin may represent a therapeutic strategy for muscle atrophy associated with type 1 DM.

