Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MiRNA expression in adipose tissue and liver from a spontaneous rat model of Type 2 diabetes

ABSTRACT: MicroRNAs (miRNAs) are non-coding RNA molecules involved in post-transcriptional control of gene expression of a wide number of genes, including those involved in glucose homeostasis. Type 2 diabetes (T2D) is characterized by hyperglycaemia and defects in insulin secretion and action at target tissues. Using a miRNA microarray platform, we sought to establish differences in miRNA expression in two insulin-target tissues (liver and adipose tissue) from seven-month-old spontaneously diabetic (Goto-Kakizaki [GK]) and non-diabetic (Brown-Norway [BN]) rats. MiRNA data were integrated with gene expression data from the same rats to investigate how differentially expressed miRNAs affected the expression of their predicted target genes. Two-colour experiment comparing GK and BN rat strains for two different tissues. Biological replicates: 4 GK and 4 BN rats; adipose tissue and liver extracted from each rat. Two samples were hybridised to each array (one of each strain, same tissue)

ORGANISM(S): Rattus norvegicus

SUBMITTER: Carme Camps

PROVIDER: E-GEOD-17058 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Herrera Blanca M BM Lockstone Helen E HE Taylor Jennifer M JM Wills Quin F QF Kaisaki Pamela J PJ Barrett Amy A Camps Carme C Fernandez Christina C Ragoussis Jiannis J Gauguier Dominique D McCarthy Mark I MI Lindgren Cecilia M CM

BMC medical genomics 20090818

<h4>Background</h4>MicroRNAs (miRNAs) are non-coding RNA molecules involved in post-transcriptional control of gene expression of a wide number of genes, including those involved in glucose homeostasis. Type 2 diabetes (T2D) is characterized by hyperglycaemia and defects in insulin secretion and action at target tissues. We sought to establish differences in global miRNA expression in two insulin-target tissues from inbred rats of spontaneously diabetic and normoglycaemic strains.<h4>Methods</h4 ...[more]

PMID: 19689793

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Project description:A need exists for biomarkers in T1D that can 1) sensitively and specifically detect disease-related immune activity prior to, and independent of, measurement of auto-antibodies towards islet cell antigens; 2) define immunopathological mechanisms; and 3) monitor changes in the inflammatory state associated with disease progression or response to therapeutic intervention. In an effort to fill this gap, we have applied a novel bioassay to both human and BB rat T1D whereby the complex milieu of inflammatory mediators present in plasma can be indirectly detected through their ability to drive transcription in peripheral blood mononuclear cells (PBMCs) drawn from healthy, unrelated donors. The resultant gene expressions are comprehensively measured with a microarray. In our human studies, we find that plasma of recent-onset T1D patients induces expression of a pro-inflammatory signature consisting in part of many interleukin-1 (IL-1) regulated genes related to immunological activation and immunocyte chemotaxis compared to unrelated healthy controls. This signature has been found to resolve in long-standing T1D subjects (>10 years post-onset), thus associating it with active autoimmunity. Importantly, this signature has been detected in pre-onset samples of progressors to T1D years prior to onset and prior to development of auto-antibodies directed towards islet antigens. In applying this approach to the BN rat, we observed that samples collected from both sub-strains at 60 days of age induced transcription of genes encoding cytokines, immune receptors, and signaling molecules consistent with a their shared susceptibility and immune activation. The DRlyp/lyp signature was differentiated from that of the DR+/+ by more robust induction of many interleukin (IL)-1M-bM-^@M-^Sregulated genes. Treatment of DRlyp/lyp rats with IL-1 receptor antagonist (IL-1RN) delayed onset and, in part, normalized the signature, suggesting that this approach may prove useful in monitoring the effect of therapeutic interventions in human T1D. Consistent with the presence of TREG cells in DR+/+ rats, we observed induction of a signature possessing negative regulators of transcription and inflammation. Fresh PBMCs of healthy Brown Norway (BN) rats (~180 days old males, to avoid variation introduced by estrous or pubertal status) were isolated by density gradient centrifugation. Transcription was induced by culturing PBMCs for 6 h at 37M-BM-0C in 5% CO2 with 20% allogeneic BN (healthy-unrelated control), DRlyp/lyp, or DR+/+ plasma [PMID 18209091]. DRlyp/lyp and DR+/+ Plasma was pooled at various ages (30, 40, 50, 60 days old) to represent timepoints prior to onset in the DRlyp/lyp strain.

Dataset Information

MiRNA expression in adipose tissue and liver from a spontaneous rat model of Type 2 diabetes

Publications

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

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