Study of long non-coding RNA and mitochondrial dysfunction in diabetic rats

Sultan, Haytham K.; Elayat, Wael M.; AbouGhalia, Azza H; Lasheen, Noha N.; Moustafa, Amr Soliman

doi:10.1016/j.tice.2021.101516

Cited by 13 publications

(7 citation statements)

References 50 publications

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“…Furthermore, reduced EGR1 expression inhibits H19 expression, thus forming a negative feedback loop that is required to maintain the homeostasis of vitamin D receptor and reducing the incidence of DN [49]. In diabetic rats with cardiac and renal complications, lncRNA H19 and Mfn-2 mRNA showed altered expression with a statistically significant downregulation of Mfn-2 mRNA expression in renal tissues [50]. In a case-control study, lncRNA H19 expressions were increased in CKD patients which had a significant correlation with decreased inflammation, glomerular filtration rate in these patients [51].…”

Section: The Functions Of H19 In Diabetic Nephropathymentioning

confidence: 99%

Recent Advances of LncRNA H19 in Diabetes

Wang

Sun

2022

Horm Metab Res

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Diabetes mellitus (DM) causes damage to major organs, including the heart, liver, brain, kidneys, eyes, and blood vessels, threatening the health of the individuals. Emerging evidence has demonstrated that lncRNAs has important functions in the pathogenesis of human diseases, such as cancers, neurodegenerative diseases, cardiac fibroblast phenotypes, hypertension, heart failure, atherosclerosis and diabetes. Recently, H19, a lncRNA, has been reported to shown to participate in the regulatory process of muscle differentiation, glucose metabolism, and tumor metastasis, as well as endometrial development. However, the roles of H19 in DM were still not completely understood. This review was conducted to summarize the functions of H19 in diabetes and discuss the challenges and possible strategies of H19 in DM.

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Section: The Functions Of H19 In Diabetic Nephropathymentioning

confidence: 99%

Recent Advances of LncRNA H19 in Diabetes

Wang

Sun

2022

Horm Metab Res

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“…In hyperglycemia, transfection of Gm10451 siRNA into islet β- cells inhibited the expression of Gm10451 and reversed those changes before. In addition, diabetes is closely linked to oxidative stress, which causes an excess of free radicals such as reactive oxygen species and is responsible for the dynamic imbalance between oxidative and antioxidant systems, which causes inflammation and damage to pancreatic tissue; then reduces the activity of SOD, an important antioxidant enzyme that scavenge oxygen free radicals, exacerbates inflammation and ultimately leads to apoptosis and damage of MIN6 cells ( Gong et al, 2021 ; Kim et al, 2021 ; Sultan et al, 2021 ). Our results were sufficient to prove that hyperglycemia promotes ROS production and reduces SOD activity of islet β cells; whereas, in this environment, a downregulation to the Gm10451 expression in pancreatic β-cells improves SOD activity, suppresses ROS content, and alleviates oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

The regulatory effect and molecular mechanism of lncRNA Gm10451 on islet cell dysfunction in children with diabetes

Wang

Zhang²,

Kang³

et al. 2022

Front. Genet.

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The dysfunction of islet β-cells is one of the causes of diabetes, and lncRNA Gm10451 is also a participant in the occurrence and the development of various diseases. This study was carried out to reveal the correlation within β-cells and Gm10451. Our study was started with the cellular cultivation of MIN6 cells in vitro, where this islet β-cell line was randomly divided into the groups of control, hyperglycemia, Gm10451 siRNA tansfection, and Gm10451 tansfection. Of all these treatments, cells in the groups of Gm10451 siRNA tansfection and Gm10451 tansfection were given with lentiviral transfection under hyperglycemia condition. Further explorations were established using PCR assay and MTT method to evaluate Gm10451 expression and estimate cellular proliferation. It ended up with the enzyme-linked immunosorbent assay (ELISA) to assess Caspase 3 activity, superoxide dismutase (SOD) activity, and reactive oxygen species (ROS) content and the secretion of IL-10 and IL-1. It was found that Gm10451 expression in MIN6 cells under hyperglycemia cultivation was notably higher than the control group; likewise, a transfection with the lentivirus of Gm10451 also resulted in the upregulation of Gm10451 expression, succeeded with inhibiting cellular proliferation, enhancing Caspase 3 activity, and decreasing SOD activity. In the lentivirus transfection groups, transfection of Gm10451 elevated the ROS content and promoted IL-1 expression, and it also decreased both IL-10 expression and insulin secretion, leading to a consequence of statistically significant difference in contrast to the high-glucose group; on the contrary, transfection of Gm10451 siRNA in a high-glucose environment downregulated the expression of Gm10451 and inversed those change before, whose results were statistically significant when compared with the high-glucose group. Hyperglycemia promotes the expression of Gm10451. Targeting inhibition toward Gm10451 alleviates cellular apoptosis and the oxidative stress of islet cells, promoting proliferation and insulin secretion of islet cells.

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“…In addition, metformin increases GAS5 expression in HepG2 cells and the plasma of patients with T2DM ( Parvar et al, 2023 ), and elevated GAS5 decreases mitochondrial tricarboxylic acid flux by disrupting the metabolic enzyme tandem of the tricarboxylic acid cycle ( Sang et al, 2021 ), providing another explanation for the mitochondrial inhibition effects of metformin. Moreover, metformin decreases the expression of H19, while H19 has been shown to downregulate the expression of Mfn-2, a key protein for mitochondrial fusion, in type 1 diabetic renal tissues ( Sultan et al, 2021 ), and a decline in Mfn2 was observed in both type 1 and type 2 diabetic rodents ( Gao et al, 2012 ; Veeranki et al, 2016 ), suggesting that metformin may regulate Mfn2 by decreasing H19.…”

Section: The Anti-diabetic Action Of Metformin Mediated By Lncrnasmentioning

confidence: 99%

The anti-diabetic effects of metformin are mediated by regulating long non-coding RNA

Chang,

Li,

2023

Front. Pharmacol.

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Type 2 diabetes (T2D) is a metabolic disease with complex etiology and mechanisms. Long non-coding ribonucleic acid (LncRNA) is a novel class of functional long RNA molecules that regulate multiple biological functions through various mechanisms. Studies in the past decade have shown that lncRNAs may play an important role in regulating insulin resistance and the progression of T2D. As a widely used biguanide drug, metformin has been used for glucose lowering effects in clinical practice for more than 60 years. For diabetic therapy, metformin reduces glucose absorption from the intestines, lowers hepatic gluconeogenesis, reduces inflammation, and improves insulin sensitivity. However, despite being widely used as the first-line oral antidiabetic drug, its mechanism of action remains largely elusive. Currently, an increasing number of studies have demonstrated that the anti-diabetic effects of metformin were mediated by the regulation of lncRNAs. Metformin-regulated lncRNAs have been shown to participate in the inhibition of gluconeogenesis, regulation of lipid metabolism, and be anti-inflammatory. Thus, this review focuses on the mechanisms of action of metformin in regulating lncRNAs in diabetes, including pathways altered by metformin via targeting lncRNAs, and the potential targets of metformin through modulation of lncRNAs. Knowledge of the mechanisms of lncRNA modulation by metformin in diabetes will aid the development of new therapeutic drugs for T2D in the future.

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Study of long non-coding RNA and mitochondrial dysfunction in diabetic rats

Cited by 13 publications

References 50 publications

Recent Advances of LncRNA H19 in Diabetes

Recent Advances of LncRNA H19 in Diabetes

The regulatory effect and molecular mechanism of lncRNA Gm10451 on islet cell dysfunction in children with diabetes

The anti-diabetic effects of metformin are mediated by regulating long non-coding RNA

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