MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes

Herrera, Blanca; Lockstone, Helen; Taylor, Jennifer; Wills, Quin F.; Kaisaki, Pamela J.; Barrett, Amy; Camps, Carme; Fernández, Christina; Ragoussis, Jiannis; Guyader, Dominique; McCarthy, Mark I.; Lindgren, Cecilia M.

doi:10.1186/1755-8794-2-54

Cited by 107 publications

(79 citation statements)

References 49 publications

(57 reference statements)

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“…An miR-29 paralog (miR29a) was differentially expressed in visceral adipose tissue between GK and control rats (26), and a series of experiments indicated altered expression of miR-125a in visceral adipose tissue of HFD mice and in 3T3-L1 adipocytes (10). In addition, expression of miR-125a was downregulated in subcutaneous adipose tissue of obese patients, regardless of their diabetes status.…”

Section: Mirna-mediated Regulation Of Insulin Sensitivity In Adipose mentioning

confidence: 91%

“…Microarray-based profiling of miRNA expression in adipose tissue in animal models and obese patients has provided information on collections of known miRNAs that are differentially expressed in obesity (25,26,51,81), including miRNAs consistently differentially expressed in various rodent models (e.g., miR-27a, miR-103, miR-107) and in both models and humans (e.g., miR-15a, miR-30d). An miR-29 paralog (miR29a) was differentially expressed in visceral adipose tissue between GK and control rats (26), and a series of experiments indicated altered expression of miR-125a in visceral adipose tissue of HFD mice and in 3T3-L1 adipocytes (10).…”

Section: Mirna-mediated Regulation Of Insulin Sensitivity In Adipose mentioning

confidence: 99%

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Biological roles of microRNAs in the control of insulin secretion and action

Caldérari

Diawara

Garaud

et al. 2017

Physiological Genomics

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microRNAs (miRNAs) are intracellular and circulating molecular components contributing to genome expression control through binding mRNA targets, which generally results in downregulated mRNA expression. One miRNA can target several mRNAs, and one transcript can be targeted by several miRNAs, resulting in complex fine-tuning of regulation of gene networks and signaling pathways. miRNAs regulate metabolism, adipocyte differentiation, pancreatic development, β-cell mass, insulin biosynthesis, secretion, and signaling, and their role in diabetes and obesity is emerging. Their pathophysiological effects are essentially dependent on cellular coexpression with their mRNA targets, which can show tissue-specific transcriptional responses to disease conditions and environmental challenges. Current knowledge of miRNA biology and their impact on the pathogenesis of diabetes and obesity is based on experimental data documenting miRNA expression generally in single tissue types that can be correlated with expression of target mRNAs to integrate miRNA in functional pathways and gene networks. Here we present results from the most significant studies dealing with miRNA function in liver, fat, skeletal muscle, and endocrine pancreas and their implication in diabetes and obesity

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Section: Mirna-mediated Regulation Of Insulin Sensitivity In Adipose mentioning

confidence: 91%

Section: Mirna-mediated Regulation Of Insulin Sensitivity In Adipose mentioning

confidence: 99%

Biological roles of microRNAs in the control of insulin secretion and action

Caldérari

Diawara

Garaud

et al. 2017

Physiological Genomics

Self Cite

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“…Indeed, previous studies have shown that the expression of the miR-125 family is modulated by diabetes. Indeed, miR-125b is upregulated in vascular smooth muscle of diabetic db/db mice (Villeneuve et al 2010) and miR-125a is increased in liver and adipose tissue of diabetic GK rats (Herrera et al 2009). Moreover, an overexpression of miR-125a and miR-125b led to the alteration of insulin signaling pathways by reducing the insulin-dependent Akt and ERK1/2 phosphorylation in SKBR3 cell line (Scott et al 2007).…”

Section: Figurementioning

confidence: 99%

Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs

Benoît¹,

Ould-Hamouda²,

Crépin³

et al. 2013

Journal of Endocrinology

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Perinatal leptin impairment has long-term consequences on energy homeostasis leading to body weight gain. The underlying mechanisms are still not clearly established. We aimed to analyze the long-term effects of early leptin blockade. In this study, newborn rats received daily injection of a pegylated rat leptin antagonist (pRLA) or saline from day 2 (d2) to d13 and then body weight gain, insulin/leptin sensitivity, and expression profile of microRNAs (miRNAs) at the hypothalamic level were determined at d28, d90, or d153 (following 1 month of high-fat diet (HFD) challenge). We show that pRLA treatment predisposes rats to overweight and promotes leptin/insulin resistance in both hypothalamus and liver at adulthood. pRLA treatment also modifies the hypothalamic miRNA expression profile at d28 leading to the upregulation of 34 miRNAs and the downregulation of four miRNAs. For quantitative RT-PCR confirmation, we show the upregulation of rno-miR-10a at d28 and rno-miR-200a, rno-miR-409-5p, and rno-miR-125a-3p following HFD challenge. Finally, pRLA treatment modifies the expression of genes involved in energy homeostasis control such as UCPs and AdipoRs. In pRLA rat muscle, Ucp2/3 and Adipor1/r2 are upregulated at d90. In liver, pRLA treatment upregulates Adipor1/r2 following HFD challenge. These genes are known to be involved in insulin resistance and type 2 diabetes. In conclusion, we demonstrate that the impairment of leptin action in early life promotes insulin/leptin resistance and modifies the hypothalamic miRNA expression pattern in adulthood, and finally, this study highlights the potential link between hypothalamic miRNA expression pattern and insulin/leptin responsiveness.

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“…Insulin resistance indicates that the peripheral tissues fail to respond to the normal level of insulin, and manifests as an elevated glucose level with decreased insulin-mediated glucose uptake in the skeletal muscle and adipose tissue, and as an impaired suppression of glucose output in the liver (Peppa et al 2010). Herrera et al (2009Herrera et al ( , 2010 profiled a cluster of miRNAs in insulin target tissues in Goto-Kakizaki (GK) rats, a spontaneous rat model of T2D, and found upregulation of miR-222 and miR-27a in adipose tissue; upregulation of miR-125a, miR-195, and miR-103 in liver; and downregulation of miR-10b in muscle.…”

Section: Mirnas and Insulin Resistancementioning

confidence: 99%

Application of microRNAs in diabetes mellitus

Chen¹,

Lan²,

Roukos³

et al. 2014

Journal of Endocrinology

107

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MicroRNAs (miRNAs) are small molecules negatively regulating gene expression by diminishing their target mRNAs. Emerging studies have shown that miRNAs play diverse roles in diabetes mellitus. Type 1 diabetes (T1D) and T2D are two major types of diabetes. T1D is characterized by a reduction in insulin release from the pancreatic b-cells, while T2D is caused by islet b-cell dysfunction in response to insulin resistance. This review describes the miRNAs that control insulin release and production by regulating cellular membrane electrical excitability (ATP:ADP ratio), insulin granule exocytosis, insulin synthesis in b-cells, and b-cell fate and islet mass formation. This review also examines miRNAs involved the insulin resistance of liver, fat, and skeletal muscle, which change insulin sensitivity pathways (insulin receptors, glucose transporter type 4, and protein kinase B pathways). This review discusses the potential application of miRNAs in diabetes, including the use of gene therapy and therapeutic compounds to recover miRNA function in diabetes, as well as the role of miRNAs as potential biomarkers for T1D and T2D.

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MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes

Cited by 107 publications

References 49 publications

Biological roles of microRNAs in the control of insulin secretion and action

Biological roles of microRNAs in the control of insulin secretion and action

Early leptin blockade predisposes fat-fed rats to overweight and modifies hypothalamic microRNAs

Application of microRNAs in diabetes mellitus

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