Oxamate Enhances the Anti-Inflammatory and Insulin-Sensitizing Effects of Metformin in Diabetic Mice

Wu, Muchao; Ye, Weiran; Zheng, Yijia; Zhang, Shanshan

doi:10.1159/000478909

Cited by 7 publications

(2 citation statements)

References 35 publications

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“…This direct anti-inflammatory effect can improve the symptoms of type 2 diabetes and is also beneficial to cardiovascular and other chronic diseases (40). The traditional anti-diabetic drug metformin has also been proved to have anti-inflammatory effects in diabetes (41). In addition to caloric therapy, changing the nutritional structure may also contribute to the improvement of insulin resistance (42).…”

Section: Discussionmentioning

confidence: 99%

Intermittent fasting therapy promotes insulin sensitivity by inhibiting NLRP3 inflammasome in rat model

et al. 2021

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Background: Substantial studies have demonstrated that fasting therapy (FT) can inhibit the inflammatory response and improve insulin resistance (IR); however, the underlying mechanisms are still unclear. This study aimed to explore the related mechanisms of intermittent FT for the treatment of IR.Methods: A rat IR model was established through collaboration of a high-fat diet with streptozotocin (STZ) injection. 8 rats were treated with intermittent FT. A positive control group was treated with metformin (MET). Mouse 3T3-L1 pre-adipocytes were cultured and induced into adipocytes in vitro, and were used as the cellular IR model. Blood insulin, glucose, and homeostatic model assessment (HOMA)-IR index were determined. Enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect inflammatory markers. Oil Red O staining determined the lipid accumulation. An NLRP3 inflammasome agonist served to investigate the effects of FT on IR in 3T3-L1 adipocytes. Results:The high levels of blood insulin, glucose, and HOMA-IR induced by high-fat diet and STZ were significantly decreased by FT. The FT also reduced the level of C-reactive protein (CRP), interleukin (IL)-1β, IL-18, caspase-1, and increased the expression of glucose transporter 1 (GLUT1), insulin receptor substrate 1 (IRS1), and IRS2 in both the rat models and 3T3-L1 adipocytes. In addition, FT significantly relieved lipid accumulation in the liver of rats. Application of NLRP3 inflammasome agonist weakened the effect of FT on IR in the IR 3T3-L1 adipocytes.Conclusions: These results suggest that FT can ameliorate the high-fat diet-and STZ-induced IR in rats through inhibition of NLRP3 inflammasome.

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Section: Discussionmentioning

confidence: 99%

Intermittent fasting therapy promotes insulin sensitivity by inhibiting NLRP3 inflammasome in rat model

et al. 2021

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“…It is front-line treatment of type-2 diabetes mellitus. Recently, it has been shown that MET not only improves insulin resistance [ 44 ] but also has anti-cancer [ 45 ], anti-inflammatory [ 46 , 47 ] and other activities. Studies have revealed MET to have an anti-inflammatory role because it reduces the level of proinflammatory factors, increases the level of anti-inflammatory factors, and inhibits oxidative stress [ 48 ].…”

Section: Introductionmentioning

confidence: 99%

Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

Tao

Zhou

Wang

et al. 2022

Korean J Physiol Pharmacol

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Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

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Extrinsic and Intrinsic Immunometabolism Converge: Perspectives on Future Research and Therapeutic Development for Obesity

Caslin

Hasty

2019

Curr Obes Rep

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Oxamate Enhances the Anti-Inflammatory and Insulin-Sensitizing Effects of Metformin in Diabetic Mice

Cited by 7 publications

References 35 publications

Intermittent fasting therapy promotes insulin sensitivity by inhibiting NLRP3 inflammasome in rat model

Intermittent fasting therapy promotes insulin sensitivity by inhibiting NLRP3 inflammasome in rat model

Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

Extrinsic and Intrinsic Immunometabolism Converge: Perspectives on Future Research and Therapeutic Development for Obesity

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