Role and therapeutic potential of microRNAs in diabetes

Kolfschoten, Ingrid; Roggli, E.; Nesca, Valeria; Regazzi, Romano

doi:10.1111/j.1463-1326.2009.01118.x

Cited by 63 publications

(43 citation statements)

References 79 publications

(112 reference statements)

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“…101 miRNA inhibitors miRNAs are considered potential pharmacological agents for the treatment of diabetes. 102,103 Two main miRNA-based therapeutic approaches have been developed for diabetes: overexpression of miRNAs using chemically synthesized miRNA mimics and inhibition of miRNAs by specific inhibitors. 103 The antisense oligonucleotide 2 0 -O-methyl-miR-375 increases the expression of its target gene 3 0 -phosphoinositide-dependent protein kinase-1 (PDK-1) and reverts insulin release back to normality in vitro.…”

Section: Nct02046395mentioning

confidence: 99%

“…102,103 Two main miRNA-based therapeutic approaches have been developed for diabetes: overexpression of miRNAs using chemically synthesized miRNA mimics and inhibition of miRNAs by specific inhibitors. 103 The antisense oligonucleotide 2 0 -O-methyl-miR-375 increases the expression of its target gene 3 0 -phosphoinositide-dependent protein kinase-1 (PDK-1) and reverts insulin release back to normality in vitro. 104 Inhibition of miR-103 and miR-107 by 2 0 -O-methyl-miR-103 and ¡107 antisense oligonucleotides improves glucose homeostasis and insulin sensitivity in mice (Fig.…”

Section: Nct02046395mentioning

confidence: 99%

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Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

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Section: Nct02046395mentioning

confidence: 99%

Section: Nct02046395mentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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“…There is growing evidence that miRNAs regulate key biological processes in the pancreatic islet (13,14,17,27,33,49). For example, miR-375, the first miRNA identified in ␤-cell function, regulates insulin secretion and is essential for normal glucose homeostasis and turnover of ␣-and ␤-cells (40, 41).…”

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confidence: 99%

miR-24 regulates menin in the endocrine pancreas

Vijayaraghavan

Maggi

Crabtree

2014

American Journal of Physiology-Endocrinology and Metabolism

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Vijayaraghavan J, Maggi EC, Crabtree JS. miR-24 regulates menin in the endocrine pancreas. Am J Physiol Endocrinol Metab 307: E84 -E92, 2014. First published May 13, 2014; doi:10.1152/ajpendo.00542.2013.-Menin, the product of the MEN1 gene, functions as a tumor suppressor and was first identified in 1997 due to its causative role in the endocrine tumor disorder multiple endocrine neoplasia, type 1 (MEN1). More recently, menin has been identified as a key player in pancreatic islet biology with the observation of an inverse relationship between menin levels and pancreatic islet proliferation. However, the factors regulating menin and the MEN1 gene in the pancreas are poorly understood. Here, we describe the regulation of menin by miR-24 and demonstrate that miR-24 directly decreases menin levels and impacts downstream cell cycle inhibitors in MIN6 insulinoma cells and in ␤lox5 immortalized ␤-cells. This regulation of menin impacts cell viability and proliferation in ␤lox5 cells. Furthermore, our data show a feedback regulation between miR-24 and menin that is present in the pancreas, suggesting that miR-24 regulates menin levels in the pancreatic islet. menin; MEN1; pancreatic islet; miR-24; miRNA THE ENDOCRINE PANCREAS is responsible for maintaining normal glucose homeostasis through the tightly controlled, regulated release of insulin from the pancreatic islet. Pancreatic islets have the unique ability to dynamically and reversibly expand to adapt to changes in insulin demand through careful balance of cell growth and renewal (including ␤-cell replication, neogenesis, transdifferentiation, and hypertrophy), and cell death (apoptosis, atrophy, and autophagy). When this process becomes compromised, it leads to the clinical manifestation of gestational diabetes or type 2 diabetes (T2D). However, detailed knowledge of the mechanisms underlying this process is lacking.MicroRNAs (miRNAs), an evolutionarily conserved class of posttranscriptional regulators, are short ϳ22-nucleotide noncoding RNA sequences that regulate the expression of mRNA targets by binding to the 3=-UTR and inhibiting translation and/or targeting the mRNA for degradation. There is growing evidence that miRNAs regulate key biological processes in the pancreatic islet (13,14,17,27,33,49). For example, miR-375, the first miRNA identified in ␤-cell function, regulates insulin secretion and is essential for normal glucose homeostasis and turnover of ␣-and ␤-cells (40, 41). Other recent studies indicate a role for miR-338-3p and miR-181a in ␤-cell differentiation and insulin sensitivity, respectively (7, 23). p38 (MAPK) is downregulated by miR-24 through the insulinresponsive glucose transporter 4 (GLUT4) to affect peripheral insulin resistance (21). miR-24 also regulates insulin production by targeting the insulin transcriptional repressors Sox6 and Bhlhe22 (35).

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“…Overall, our data suggest that miR-381 is a viable therapeutic target for preventing cartilage degradation. Therapeutic strategies incorporating microRNA have been applied in several disease states, including cancer, diabetes, and cardiovascular disease [56,57,58]. miR-155 has also been targeted recently as a therapeutic in inflammatory diseases including rheumatoid arthritis [59].…”

Section: Discussionmentioning

confidence: 99%

The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses

Hou

Meng

Zhang

et al. 2015

Cell Physiol Biochem

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Aim: The molecular pathways regulating cartilage degradation are unclear. miR-381 was identified as a putative regulator of chondrogenesis related genes. Here, we examined its role in chondrogenesis and osteoarthritic cartilage degeneration. Methods: miR-381 expression was assessed in vitro in response to IL-1β stimulation in primary human (PHC) and mouse (PMC) chondrocytes, and ATDC5 derived chondrocytes; and in vivo in mouse embryos and human osteoarthritic cartilage. The effects of miR-381 on chondrogenesis and NF-kB signaling were assessed using a synthetic RNA mimic or inhibitor and luciferase assay, respectively. Upstream regulators of miR381 were probed using siRNA or overexpression plasmids for Sox9 and Runx2. Results: miR-381 expression was elevated in chondrogenic and hypertrophic ATDC5 cells. miR-381 was induced in vitro by IL-1β in ATDC5 cells, PMCs, and PHCs, and was expressed in areas of cartilage degradation or absorption in vivo. Overexpression of Runx2 or Sox9 increased miR-381 expression in ATDC5 cells. miR-381 suppressed expression of collagen, type II, alpha 1, and enhanced expression of metalloproteinase-13 (MMP-13), but did not regulate NFKBIA and NKRF activity. Conclusion: miR-381 was highly expressed during chondrogenesis and in arthritic cartilage. It may contribute to absorption of the cartilage matrix by repressing type II collagen and inducing MMP-13.

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Role and therapeutic potential of microRNAs in diabetes

Cited by 63 publications

References 79 publications

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

miR-24 regulates menin in the endocrine pancreas

The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses

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