Exercise training-attenuated insulin resistance and liver injury in elderly pre-diabetic patients correlates with NLRP3 inflammasome

Zhang, Tan; Tian, Jing; Fan, Jingcheng; Liu, Xiangyun; Wang, Ru

doi:10.3389/fimmu.2023.1082050

Cited by 6 publications

(7 citation statements)

References 48 publications

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“…The study found that high sensitivity CRP and IL-18 decreased and IL-10 increased in DM patients in the exercise group compared with the control group. 263 12 weeks of Tai chi training 264 or 6 months of exercise 265 could decrease the activity of NLRP3 inflammasome and related inflammatory cytokines like IL-1β and IL-18 in prediabetic patients to alleviate systemic inflammation, reduce blood glucose, and improve IR. A single dose of high-intensity interval training (HIIT) had obvious anti-inflammatory effects on patients with T2DM, which was characterized by the decrease of TNF-α and TLR2 surface protein.…”

Section: Healthy Diet and Exercisementioning

confidence: 99%

Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions

Zhao,

Hu,

Zhang

et al. 2024

MedComm

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At present, diabetes mellitus (DM) has been one of the most endangering healthy diseases. Current therapies contain controlling high blood sugar, reducing risk factors like obesity, hypertension, and so on; however, DM patients inevitably and eventually progress into different types of diabetes complications, resulting in poor quality of life. Unfortunately, the clear etiology and pathogenesis of diabetes complications have not been elucidated owing to intricate whole‐body systems. The immune system was responsible to regulate homeostasis by triggering or resolving inflammatory response, indicating it may be necessary to diabetes complications. In fact, previous studies have been shown inflammation plays multifunctional roles in the pathogenesis of diabetes complications and is attracting attention to be the meaningful therapeutic strategy. To this end, this review systematically concluded the current studies over the relationships of susceptible diabetes complications (e.g., diabetic cardiomyopathy, diabetic retinopathy, diabetic peripheral neuropathy, and diabetic nephropathy) and inflammation, ranging from immune cell response, cytokines interaction to pathomechanism of organ injury. Besides, we also summarized various therapeutic strategies to improve diabetes complications by target inflammation from special remedies to conventional lifestyle changes. This review will offer a panoramic insight into the mechanisms of diabetes complications from an inflammatory perspective and also discuss contemporary clinical interventions.

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Section: Healthy Diet and Exercisementioning

confidence: 99%

Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions

Zhao,

Hu,

Zhang

et al. 2024

MedComm

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“…Although the role of NLRP3 in the exercise regulation of diabetic skeletal muscle is still unclear, recent studies have confirmed that the NLRP3 inflammasome is related to the pathogenesis of T2DM, and that by inhibiting inflammasome activation in adipose tissue and the liver, it can enhance insulin signaling [45]. Exercise training may reduce insulin resistance and liver injury in elderly prediabetic subjects by inhibiting the activity of the NLRP3 inflammasome [46].…”

Section: Mcc950 Treatment and Aerobic Exercise Moderates The Levels O...mentioning

confidence: 99%

MCC950 Ameliorates Diabetic Muscle Atrophy in Mice by Inhibition of Pyroptosis and Its Synergistic Effect with Aerobic Exercise

Yan,

Fu,

Zhang

et al. 2024

Molecules

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Diabetic muscle atrophy is an inflammation-related complication of type-2 diabetes mellitus (T2DM). Even though regular exercise prevents further deterioration of atrophic status, there is no effective mediator available for treatment and the underlying cellular mechanisms are less explored. In this study, we investigated the therapeutic potential of MCC950, a specific, small-molecule inhibitor of NLRP3, to treat pyroptosis and diabetic muscle atrophy in mice. Furthermore, we used MCC950 to intervene in the protective effects of aerobic exercise against muscle atrophy in diabetic mice. Blood and gastrocnemius muscle (GAS) samples were collected after 12 weeks of intervention and the atrophic state was assessed. We initially corroborated a diabetic muscle atrophy phenotype in db/db mice (D) by comparison with control m/m mice (W) by examining parameters such as fasting blood glucose (D vs. W: 24.47 ± 0.45 mmol L−1 vs. 4.26 ± 0.6 mmol L−1, p < 0.05), grip strength (D vs. W: 166.87 ± 15.19 g vs. 191.76 ± 14.13 g, p < 0.05), exercise time (D vs. W: 1082.38 ± 104.67 s vs. 1716 ± 168.55 s, p < 0.05) and exercise speed to exhaustion (D vs. W: 24.25 ± 2.12 m min−1 vs. 34.75 ± 2.66 m min−1, p < 0.05), GAS wet weight (D vs. W: 0.07 ± 0.01 g vs. 0.13 ± 0.01 g, p < 0.05), the ratio of GAS wet weight to body weight (D vs. W: 0.18 ± 0.01% vs. 0.54 ± 0.02%, p < 0.05), and muscle fiber cross-sectional area (FCSA) (D vs. W: 1875 ± 368.19 µm2 vs. 2747.83 ± 406.44 µm2, p < 0.05). We found that both MCC950 (10 mg kg−1) treatment and exercise improved the atrophic parameters that had deteriorated in the db/db mice, inhibited serum inflammatory markers and significantly attenuated pyroptosis in atrophic GAS. In addition, a combined MCC950 treatment with exercise (DEI) exhibited a further improvement in glucose uptake capacity and muscle performance. This combined treatment also improved the FCSA of GAS muscle indicated by Laminin immunofluorescence compared to the group with the inhibitor treatment alone (DI) (DEI vs. DI: 2597 ± 310.97 vs. 1974.67 ± 326.15 µm2, p < 0.05) or exercise only (DE) (DEI vs. DE: 2597 ± 310.97 vs. 2006.33 ± 263.468 µm2, p < 0.05). Intriguingly, the combination of MCC950 treatment and exercise significantly reduced NLRP3-mediated inflammatory factors such as cleaved-Caspase-1, GSDMD-N and prevented apoptosis and pyroptosis in atrophic GAS. These findings for the first time demonstrate that targeting NLRP3-mediated pyroptosis with MCC950 improves diabetic muscle homeostasis and muscle function. We also report that inhibiting pyroptosis by MCC950 can enhance the beneficial effects of aerobic exercise on diabetic muscle atrophy. Since T2DM and muscle atrophy are age-related diseases, the young mice used in the current study do not seem to fully reflect the characteristics of diabetic muscle atrophy. Considering the fragile nature of db/db mice and for the complete implementation of the exercise intervention, we used relatively young db/db mice and the atrophic state in the mice was thoroughly confirmed. Taken together, the current study comprehensively investigated the therapeutic effect of NLRP3-mediated pyroptosis inhibited by MCC950 on diabetic muscle mass, strength and exercise performance, as well as the synergistic effects of MCC950 and exercise intervention, therefore providing a novel strategy for the treatment of the disease.

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“…Evidence shows that 12 weeks of Tai Chi intervention effectively alleviated glucose homeostasis and inhibited the expression of the NLRP3 inflammatory signal pathway in middle-aged and elderly pre-diabetic patients ( 107 ). Moreover, the combined of Yijinjing and resistance training has proven effective in inhibiting the robust NLRP3 inflammasome activation, thereby alleviating insulin resistance and liver injury in elderly pre-diabetes ( 108 ). Research has also shown that exercise can exert an anti-inflammatory effect by reducing circulating levels of inflammasome activation-related inflammatory cytokines IL-1β and IL-18 in overweight/obese populations ( 109 ).…”

Section: Exercise On Improving Diabetic Complications By Targeting Py...mentioning

confidence: 99%

Exploring exercise-driven inhibition of pyroptosis: novel insights into treating diabetes mellitus and its complications

Li,

Zhang,

Wang

et al. 2023

Front. Endocrinol.

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Diabetes mellitus (DM) and its complications are important, worldwide public health issues, exerting detrimental effects on human health and diminishing both quality of life and lifespan. Pyroptosis, as a new form of programmed cell death, plays a critical role in DM and its complications. Exercise has been shown to be an effective treatment for improving insulin sensitivity or preventing DM. However, the molecular mechanisms underlying the effects of exercise on pyroptosis-related diseases remain elusive. In this review, we provided a comprehensive elucidation of the molecular mechanisms underlying pyroptosis and the potential mechanism of exercise in the treatment of DM and its complications through the modulation of anti-pyroptosis-associated inflammasome pathways. Based on the existing evidence, further investigation into the mechanisms by which exercise inhibits pyroptosis through the regulation of inflammasome pathways holds promising potential for expanding preventive and therapeutic strategies for DM and facilitating the development of novel therapeutic interventions.

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Exercise training-attenuated insulin resistance and liver injury in elderly pre-diabetic patients correlates with NLRP3 inflammasome

Cited by 6 publications

References 48 publications

Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions

Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions

MCC950 Ameliorates Diabetic Muscle Atrophy in Mice by Inhibition of Pyroptosis and Its Synergistic Effect with Aerobic Exercise

Exploring exercise-driven inhibition of pyroptosis: novel insights into treating diabetes mellitus and its complications

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