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Int. J. Mol. Sci. 2016, 17(5), 665; doi:10.3390/ijms17050665

Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats

1
Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany
2
Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 11 March 2016 / Revised: 8 April 2016 / Accepted: 26 April 2016 / Published: 3 May 2016
(This article belongs to the Special Issue Liquid Biopsy for Clinical Application)
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Abstract

The aim of the present pilot study was the identification of micro-RNA changes over time during the development and progression of type 2 diabetes (T2D) in Zucker diabetic fatty rats (ZDF rats). T2D is a complex metabolic disorder that is characterized, inter alia, by progressive failure of pancreatic β cells to produce insulin, but also by functional or morphological modifications of others organ, such as liver, adipose tissue and the cardiovascular system. Micro-RNAs are a novel class of biomarkers that have the potential to represent biomarkers of disease progression. In this study, the onset and progression of diabetes was followed in ZDF rats from six weeks until 17 weeks of age. After an initial phase of hyperinsulinemia, the animals developed T2D and lost the capacity to produce sufficient insulin. Circulating miRNAs were measured from plasma samples at four time points: pre-diabetes (six weeks of age), hyperinsulinemia (eight weeks), β cell failure (11 weeks) and late-stage diabetes (17 weeks) using TaqMan miRNA arrays. Bioinformatic analysis revealed distinct changes of circulating miRNAs over time. Several miRNAs were found to be increased over the course of the disease progression, such as miR-122, miR-133, miR-210 and miR-375. The most significantly decreased miRNAs were miR-140, miR-151-3p, miR-185, miR-203, miR-434-3p and miR-450a. Some of the miRNAs have also been identified in type 2 diabetic patients recently and, therefore, may have the potential to be useful biomarkers for the disease progression of T2D and/or the treatment response for anti-diabetic medications. View Full-Text
Keywords: ZDF rats; hyperinsulinemia; diabetes; micro-RNA; biomarker; disease progression; miR-122; miR-133a; miR-375 ZDF rats; hyperinsulinemia; diabetes; micro-RNA; biomarker; disease progression; miR-122; miR-133a; miR-375
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Delic, D.; Eisele, C.; Schmid, R.; Luippold, G.; Mayoux, E.; Grempler, R. Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats. Int. J. Mol. Sci. 2016, 17, 665.

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