Metformin alleviates long-term high-fructose diet-induced skeletal muscle insulin resistance in rats by regulating purine nucleotide cycle

Cheng, Juanjuan; Xu, Lie-Qiang; Yu, Qiuxia; Lin, Guoshu; Ma, Xingdong; Li, Mengyao; Guan, Fengkun; Liu, Yuhong; Huang, Xiaojun; Xie, Jianhui; Chen, Jiannan; Su, Ziren; Li, Yucui

doi:10.1016/j.ejphar.2022.175234

Cited by 6 publications

(5 citation statements)

References 52 publications

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“…We observed that the protein level of Nrf2 in the HFD group was dramatically reduced compared to the NCD group; however, MET and MOR could reverse this suppression, both alone and more effectively, when combined. Our results regarding MET are in agreement with the findings of Cheng et al which showed that treatment of rats fed a high-fructose diet with MET improved oxidative stress in the muscle through the AMP-activated protein kinase (AMPK)/Nrf2 pathway (Cheng et al, 2022). Also, our results regarding MOR are consistent with the data obtained from studies that proved MOR as a potent antioxidant.…”

Section: Discussionsupporting

confidence: 92%

“…Our results from the assessment of TLR-4 expression showed that the treatment with MET and MOR, and more effectively MET + MOR combined treatment, could completely reverse the increase in TLR4 expression in the HFD group. Our findings about MET are fully supported by our previous studies (Aliabadi et al, 2021;Goodarzi et al, 2023;Khalafani et al, 2023) as well as many other studies (Cao et al, 2019;Cheng et al, 2022;Jing et al, 2018;Peixoto et al, 2017) showing that MET reduces inflammation in the muscle, liver, adipose tissue, and serum. Regarding MOR, although no studies have been conducted on its anti-inflammatory effects in the muscle, its anti-inflammatory activity has generally well-established.…”

Section: Discussionsupporting

confidence: 90%

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Combination therapy of metformin and morin attenuates insulin resistance, inflammation, and oxidative stress in skeletal muscle of high‐fat diet‐fed mice

Bahramzadeh,

Samavarchi Tehrani,

Goodarzi

et al. 2023

Phytotherapy Research

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Lipid accumulation, inflammation, and oxidative stress are the most important causes of muscle insulin resistance. The aim of this study was to investigate the single and combined treatment effects of metformin (MET) and morin (MOR) on lipid accumulation, inflammation, and oxidative stress in the skeletal muscle of mice fed a high‐fat diet. The mice were supplemented with MET (230 mg/kg diet), MOR (100 mg/kg diet), and MET + MOR for 9 weeks. Our results revealed that single treatment with MET or MOR, and with a stronger effect of MET + MOR combined treatment, reduced body weight gain, improved glucose intolerance and enhanced Akt phosphorylation in the muscle tissue. In addition, plasma and muscle triglyceride levels were decreased after treatment with MET and MOR. The expression of genes involved in macrophage infiltration and polarization and pro‐inflammatory cytokines showed that MET + MOR combined treatment, significantly reduced inflammation in the muscle. Furthermore, combined treatment of MET + MOR with greater efficacy than the single treatment improved several oxidative stress markers in the muscle. Importantly, combined treatment of MET and MOR could increase the expression of nuclear factor erythroid 2–related factor 2, the master regulator of the antioxidant response. These findings suggest that combination of MET with MOR might ameliorate insulin resistance, inflammation, and oxidative stress in the skeletal muscle of mice fed high‐fat diet.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Combination therapy of metformin and morin attenuates insulin resistance, inflammation, and oxidative stress in skeletal muscle of high‐fat diet‐fed mice

Bahramzadeh,

Samavarchi Tehrani,

Goodarzi

et al. 2023

Phytotherapy Research

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“…27 In addition to the liver tissues, skeletal muscle, pancreas, and adipose tissues are also target organs of insulin, and BBR has been shown to improve high-fructose-induced IR in skeletal muscle. 28 However, the effects of BBR on obesity-induced IR in mice, particularly its effects on skeletal muscle IR and pancreatic islets insulin secretion, have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Berberine attenuates obesity‐induced insulin resistance by inhibiting miR‐27a secretion

Du,

Zhu,

Yang

et al. 2024

Diabet Med

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IntroductionBerberine (BBR) is an alkaloid found in plants. It has neuroprotective, anti‐inflammatory and lipid‐lowering activity. However, the efficacy of treatment with BBR and the mechanisms through which it acts need further study.AimsThis study investigated the therapeutic effects and the mechanism of action of BBR on obesity‐induced insulin resistance in peripheral tissues.MethodsHigh‐fat‐fed C57BL/6J mice and low‐fat‐fed C57BL/6J mice with miR‐27a overexpression were given BBR intervention (100 mg/kg, po), and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. Palmitic acid‐stimulated hypertrophic adipocyte models were treated with BBR (10 μM). Related indicators and protein expression levels were examined.ResultsThe AUCs of the OGTT and the ITT in the BBR intervention group were reduced significantly (p < 0.01) (p < 0.05), and the serum biochemical parameters, including FBG, TC, TG and LDL‐C were significantly reduced after BBR intervention. In the in vitro experiments, the triglyceride level and volume of lipid droplets decreased significantly after BBR intervention (p < 0.01) (p < 0.05). Likewise, BBR ameliorates skeletal muscle and pancreas insulin signalling pathways in vivo and in vitro.DiscussionThe results showed that BBR significantly ameliorated insulin resistance, reduced body weight and percent body fat and improved serum biochemical parameters in mice. Likewise, BBR reduced triglyceride level and lipid droplet volume in hypertrophic adipocytes, BBR improved obesity effectively. Meanwhile, BBR ameliorated the histomorphology of the pancreas, and skeletal muscle and pancreas insulin related signalling pathways of islets in in vitro and in vivo experiments. The results further demonstrated that BBR inhibited miR‐27a levels in serum from obese mice and supernatant of hypertrophic adipocytes. miR‐27a overexpression in low‐fat fed mice indicated that miR‐27a caused insulin resistance, and BBR intervention significantly improved the miR‐27a induced insulin resistance status.ConclusionThis study demonstrates the important role of BBR in obesity‐induced peripheral insulin resistance and suggest that the mechanism of its effect may be inhibition of miR‐27a secretion.

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“…The causal roles of SGLT2i in choline metabolites had been confirmed, [32] also purine metabolism for metformin monotherapy. [33] There still existed many other differences among the blood metabolites for different treatments. Our research is the first to identify the differences of blood metabolites between SGLT2i and metformin.…”

Section: Discussionmentioning

confidence: 99%

The Comparation of Renal Anti‐Senescence Effects and Blood Metabolites between Dapagliflozin and Metformin in Non‐Diabetes Environment

Zeng,

Chen,

Gao

et al. 2023

Advanced Biology

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Delaying kidney senescence process will benefit renal physiologic conditions, and prompt the kidney recovering from different pathological states. The renal anti‐senescence effects of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) and metformin have been proven in diabetic settings, but the roles of each one and combination of two drugs in natural kidney aging process remain undefined and deserve further research. Senescence‐accelerated mouse prone 8 (SAMP8) were orally administered dapagliflozin, metformin, and a combination of them for 16 weeks. Dapagliflozin exhibits better effects than metformin in lowering senescence related markers, and the combination therapy shows the best results. In vitro experiments demonstrate the same results that the combination of dapagliflozin and metformin can exert a better anti‐senescence effect. Blood metabolites detection in vivo shows dapagliflozin mainly leads to the change of blood metabolites enriched in choline metabolism, and metformin tends to induce change of blood metabolites enriched in purine metabolism. In conclusion, the results suggest dapagliflozin may have a better renal anti‐senescence effect than metformin in non‐diabetes environment, and the combination of the two drugs can strengthen the effect. The two drugs can lead to different blood metabolites alteration, which may lead to different systemic effects.

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Metformin alleviates long-term high-fructose diet-induced skeletal muscle insulin resistance in rats by regulating purine nucleotide cycle

Cited by 6 publications

References 52 publications

Combination therapy of metformin and morin attenuates insulin resistance, inflammation, and oxidative stress in skeletal muscle of high‐fat diet‐fed mice

Combination therapy of metformin and morin attenuates insulin resistance, inflammation, and oxidative stress in skeletal muscle of high‐fat diet‐fed mice

Berberine attenuates obesity‐induced insulin resistance by inhibiting miR‐27a secretion

The Comparation of Renal Anti‐Senescence Effects and Blood Metabolites between Dapagliflozin and Metformin in Non‐Diabetes Environment

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