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Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice
- Source :
- Mammalian Genome. 20:476-485
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- Type 2 diabetes results from severe insulin resistance coupled with a failure of b cells to compensate by secreting sufficient insulin. Multiple genetic loci are involved in the development of diabetes, although the effect of each gene on diabetes susceptibility is thought to be small. MicroRNAs (miRNAs) are noncoding 19-22-nucleotide RNA molecules that potentially regulate the expression of thousands of genes. To understand the relationship between miRNA regulation and obesity-induced diabetes, we quantitatively profiled approximately 220 miRNAs in pancreatic islets, adipose tissue, and liver from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mice. More than half of the miRNAs profiled were expressed in all three tissues, with many miRNAs in each tissue showing significant changes in response to genetic obesity. Furthermore, several miRNAs in each tissue were differentially responsive to obesity in B6 versus BTBR mice, suggesting that they may be involved in the pathogenesis of diabetes. In liver there were approximately 40 miRNAs that were downregulated in response to obesity in B6 but not BTBR mice, indicating that genetic differences between the mouse strains play a critical role in miRNA regulation. In order to elucidate the genetic architecture of hepatic miRNA expression, we measured the expression of miRNAs in genetically obese F2 mice. Approximately 10% of the miRNAs measured showed significant linkage (miR-eQTLs), identifying loci that control miRNA abundance. Understanding the influence that obesity and genetics exert on the regulation of miRNA expression will reveal the role miRNAs play in the context of obesity-induced type 2 diabetes.
- Subjects :
- Male
Gene Dosage
Mice, Obese
Adipose tissue
Biology
Article
Islets of Langerhans
Mice
Insulin resistance
microRNA
Gene expression
Genetics
medicine
Animals
Humans
Gene silencing
Obesity
Regulation of gene expression
Gene Expression Profiling
Pancreatic islets
medicine.disease
Gene expression profiling
Disease Models, Animal
MicroRNAs
medicine.anatomical_structure
Adipose Tissue
Diabetes Mellitus, Type 2
Gene Expression Regulation
Liver
Female
Subjects
Details
- ISSN :
- 14321777 and 09388990
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Mammalian Genome
- Accession number :
- edsair.doi.dedup.....3b8adca517d982cb589f1f55bb9361de