microRNAs and the regulation of glucose and lipid metabolism

Poy, Matthew N.; Spranger, Martina; Stoffel, Markus

doi:10.1111/j.1463-1326.2007.00775.x

Cited by 153 publications

(113 citation statements)

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“…These alterations are associated with perturbed development and pathological situations. Indeed, miRNAs seem to be major regulators of gene expression in many biological programs, including organ development and metabolism (12)(13)(14)(15)(16)(17). Computational predictions of miRNA targets estimate that a single miRNA can affect a gamut of different mRNAs, suggesting that a large proportion of the transcriptome is subjected to miRNA modulation.…”

mentioning

confidence: 99%

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

et al. 2014

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The intrauterine environment of the fetus is a preeminent actor in long-term health. Indeed, mounting evidence shows that maternal malnutrition increases the risk of type 2 diabetes (T2D) in progeny. Although the consequences of a disturbed prenatal environment on the development of the pancreas are known, the underlying mechanisms are poorly defined. In rats, restriction of protein during gestation alters the development of the endocrine pancreas and favors the occurrence of T2D later in life. Here we evaluate the potential role of perturbed microRNA (miRNA) expression in the decreased b-cell mass and insulin secretion characterizing progeny of pregnant dams fed a low-protein (LP) diet. miRNA profiling shows increased expression of several miRNAs, including miR-375, in the pancreas of fetuses of mothers fed an LP diet. The expression of miR-375 remains augmented in neoformed islets derived from fetuses and in islets from adult (3-month-old) progeny of mothers fed an LP diet. miR-375 regulates the proliferation and insulin secretion of dissociated islet cells, contributing to the reduced b-cell mass and function of progeny of mothers fed an LP diet. Remarkably, miR-375 normalization in LP-derived islet cells restores b-cell proliferation and insulin secretion. Our findings suggest the existence of a developmental memory in islets that registers intrauterine protein restriction. Hence, pancreatic failure after in utero malnutrition could result from transgenerational transmission of miRNA misexpression in b-cells.

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Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

et al. 2014

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“…Taken together, it appears that a relatively few miRNAs can regulate as much as 20 -30% of the human genome. Recently, specific miRNAs have been reported to be associated with diabetes (28,29), cancer (30 -33), heart disease (34,35), cell cycle (36), and development (17). Importantly, functional suppression of miRNAs can be achieved, both in vitro and in vivo, by antagomirs, which are chemically engineered oligonucleotides that are antisense to miRNAs (37).…”

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confidence: 99%

Elevated miR-155 Promotes Inflammation in Cystic Fibrosis by Driving Hyperexpression of Interleukin-8

Bhattacharyya

Balakathiresan²,

Dalgard

et al. 2011

Journal of Biological Chemistry

193

167

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Cystic Fibrosis (CF) is characterized by a massive proinflammatory phenotype in the lung arising from profound expression of inflammatory genes, including interleukin-8 (IL-8). We have previously reported that IL-8 mRNA is stabilized in CF lung epithelial cells, resulting in concomitant hyperexpression of IL-8 protein. However, the mechanistic link between mutations in CFTR and acquisition of the proinflammatory phenotype in the CF airway has remained elusive. We hypothesized that specific microRNAs (miRNAs) might mediate this linkage. To identify the potential link, we screened an miRNA library for differential expression in ⌬F508-CFTR and wild type CFTR lung epithelial cell lines. Of 22 differentially and significantly expressed miRNAs, we found that expression of miR-155 was more than 5-fold elevated in CF IB3-1 lung epithelial cells in culture, compared with control IB3-1/S9 cells. Clinically, miR-155 was also highly expressed in CF lung epithelial cells and circulating CF neutrophils biopsied from CF patients. We report here that high levels of miR-155 specifically reduced levels of SHIP1, thereby promoting PI3K/Akt activation. However, overexpressing SHIP1 or inhibition of PI3K in CF cells suppressed IL-8 expression. Finally, we found that phospho-Akt levels were elevated in CF lung epithelial cells and were specifically lowered by either antagomir-155 or elevated expression of SHIP1. We therefore suggest that elevated miR-155 contributes to the proinflammatory expression of IL-8 in CF lung epithelial cells by lowering SHIP1 expression and thereby activating the PI3K/Akt signaling pathway. These data suggest that miR-155 may play an important role in the activation of IL-8-dependent inflammation in CF.

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“…Many SNPs located in target sites for miRNA action are correlated with miRNA mediated metabolic disorders like Tourette's Syndrome, Spastic Paraplegia, Hypertension, Parcinson Disease and various types of cancers (Sethupathy & Collins, 2008). MiRNA dysfunction is also correlated with obesity, insulin resistance and type 2 diabetes pathogenesis (Ferland-McCollough et al, 2010;Poy et al, 2007). Genome wide association studies (GWA) as well as meta-analysis studies demonstrated several SNPs correlated with higher risk of type 2 diabetes (Salonen et al, 2007;Zeggini et al, 2008;Dupuis et al, 2010).…”

Section: Snps In Microrna Genes/ Microrna Target Sites and Insulin Rementioning

confidence: 99%

The Role of Single Nucleotide Polymorphisms of Untranslated Regions (Utrs) in Insulin Resistance Pathogenesis in Patients with Type 2 Diabetes

Małodobra¹

2011

Medical Complications of Type 2 Diabetes

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microRNAs and the regulation of glucose and lipid metabolism

Cited by 153 publications

References 50 publications

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

Elevated miR-155 Promotes Inflammation in Cystic Fibrosis by Driving Hyperexpression of Interleukin-8

The Role of Single Nucleotide Polymorphisms of Untranslated Regions (Utrs) in Insulin Resistance Pathogenesis in Patients with Type 2 Diabetes

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