Diabetes Mellitus induces alterations in metallothionein protein expression and metal levels in the testis and liver

Gu, Yiming; Lian, Xin; Sun, Weixia; Gao, Baofeng; Fu, Yue

doi:10.1177/0300060517708923

Cited by 7 publications

(5 citation statements)

References 52 publications

(73 reference statements)

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“…China as this rat model is the classic model for studying DM. 25,26 After the adaption for 4 weeks, streptozotocin (STZ,60 mg/kg; Sigma-Aldrich) was dissolved in the vehicle (0.1 mol/L citratephosphate buffer; pH = 4.2) and injected into 25 rats to induce type 1 DM. The same vehicle was injected into the other 20 rats.…”

Section: Berberine (Bb) the Major Active Component Isolated Frommentioning

confidence: 99%

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

et al. 2020

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Background: Diabetes mellitus (DM) induces impairment of male reproductive system and is considered as a key factor that could partially provide an explanation for male infertility. Thus, understanding the mechanism underlying DM-induced infertility will aid in the identification of novel therapeutic stratagems. Objectives: To delineate the role of ROS/JAK2/NFκB pathway in DM-induced low reproductive function and impaired spermatogenesis. Additionally, to investigate the protective effect of monomeric Berberine (BB) that inhibits ROS/JAK2/NFκB pathway, in the pathogenesis of DM-induced infertility.Methods: 12-week-old male Sprague-Dawley rats were divided into four groups: control group, DM group, control plus BB group, and DM plus BB group. Streptozotocin was used to induce DM. After treating the rats with BB for 4 weeks, fertility tests were conducted to investigate the reproductive function, and testis weight along with sperm motility was assessed through microscope. Oxidative stress was evaluated by DHE staining. TUNEL staining was utilized to detect the state of apoptosis. Cell experiments were carried out to define the role of BB in vitro. Immunohistochemistry, immunofluorescence, and Western blotting were employed to measure the protein expression. Results:Our results indicate that the reproductive function of DM rats was low, accompanied by decreased testis weight and sperm motility in addition to the impairment of the seminiferous tubules. However, there was a significant improvement in the reproductive function parameters in the BB-treated DM rats. Subsequently, our data revealed that DM rats produce an increased level of ROS in the testis, which activates JAK2 further activating the NFκB pathway, leading to increased apoptosis and impaired cells in the testicles. However, BB could attenuate the ROS production and abrogate activation of JAK2/NFκB pathway, thus inhibiting the apoptosis in the testicular cells of DM rats.Conclusion: ROS/JAK2/NFκB pathway is involved in the DM-induced low reproductive function and impaired spermatogenesis. BB can play a protective role in

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Section: Berberine (Bb) the Major Active Component Isolated Frommentioning

confidence: 99%

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

et al. 2020

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“…Metallothionein can be induced by a variety of conditions including high glucose (17,18), and plays a crucial role in mediating anti-apoptosis and anti-inflammation. By modulating stress- induced signaling pathways of Wnt, NF-kB, and PI3K, Metallothionein can alleviate diabetes and diabetic complications (19).…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA metallothionein 1 pseudogene 3 promotes p2y12 expression by sponging miR-126 to activate platelet in diabetic animal model

et al. 2018

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Platelet hyperaggregation and hypercoagulation are associated with increase of thrombogenic risk, especially in patients with type 2 diabetes (T2D). High activity of P2Y12 receptor is found in T2D patients, exposing such patients to a prothrombotic condition. P2Y12 is a promising target for antiplatelet, but due to P2Y12 receptor constitutive activation, the clinical practical phenomena such as "clopidogrel resistance" are commonly occurring. In this study, we investigate the role of lncRNA on platelet activation. By lncRNA array, we screened thousands of differentially expressed lncRNA in megakaryocytes from T2D patients and confirmed that lncRNA metallothionein 1 pseudogene 3 (MT1P3) was significantly upregulated in megakaryocytes from T2D patients than in healthy controls. And we further investigate the biofunction of MT1P3 on platelet activation and the regulatory mechanism on p2y12. MT1P3 was positively correlated with p2y12 mRNA levels and promoted p2y12 expression by sponging miR-126. Knockdown of MT1P3 by siRNA reduced p2y12 expression, inhibiting platelet activation and aggregation in diabetes animal model. In conclusion, our findings identify MT1P3 as a key regulator in platelet activation by increasing p2y12 expression through sponging miR-126 under T2D condition. These findings may provide a new insight for managing platelet hyperactivity-related diseases.

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“…As its safety and efficacy have been established, it should be investigated whether a-tocopherol also provides clinical benefit for the treatment of HIO in patients with NASH. However, a-tocopherol did not decrease hepatic iron contents in rats with diabetes or with iron overload (102,103) while it suppressed lipid peroxidation and ferroptosis induced by hepatic ischemia-reperfusion in rats (104). Therefore, the hepatoprotective effects of tocopherol are likely attributable solely to its antioxidant properties.…”

Section: Vitamin Ementioning

confidence: 94%

Iron-Induced Hepatocarcinogenesis—Preventive Effects of Nutrients

Tsuchiya

2022

Front. Oncol.

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The liver is a primary organ that stores body iron, and plays a central role in the regulation of iron homeostasis. Hepatic iron overload (HIO) is a prevalent feature among patients with chronic liver diseases (CLDs), including alcoholic/nonalcoholic liver diseases and hepatitis C. HIO is suggested to promote the progression toward hepatocellular carcinoma because of the pro-oxidant nature of iron. Iron metabolism is tightly regulated by various factors, such as hepcidin and ferroportin, in healthy individuals to protect the liver from such deteriorative effects. However, their intrinsic expressions or functions are frequently compromised in patients with HIO. Thus, various nutrients have been reported to regulate hepatic iron metabolism and protect the liver from iron-induced damage. These nutrients are beneficial in HIO-associated CLD treatment and eventually prevent iron-mediated hepatocarcinogenesis. This mini-review aimed to discuss the mechanisms and hepatocarcinogenic risk of HIO in patients with CLDs. Moreover, nutrients that hold the potential to prevent iron-induced hepatocarcinogenesis are summarized.

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Diabetes Mellitus induces alterations in metallothionein protein expression and metal levels in the testis and liver

Cited by 7 publications

References 52 publications

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

Long non-coding RNA metallothionein 1 pseudogene 3 promotes p2y12 expression by sponging miR-126 to activate platelet in diabetic animal model

Iron-Induced Hepatocarcinogenesis—Preventive Effects of Nutrients

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