Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats
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 pancreat...
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doaj-e91c97ab0fe64da0a2fda3c2558a24f22020-11-24T22:00:26ZengMDPI AGInternational Journal of Molecular Sciences1422-00672016-05-0117566510.3390/ijms17050665ijms17050665Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty RatsDenis Delic0Claudia Eisele1Ramona Schmid2Gerd Luippold3Eric Mayoux4Rolf Grempler5Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, GermanyDepartment of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, GermanyDepartment of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, GermanyDepartment of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, GermanyDepartment of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, GermanyDepartment of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, GermanyThe 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.http://www.mdpi.com/1422-0067/17/5/665ZDF ratshyperinsulinemiadiabetesmicro-RNAbiomarkerdisease progressionmiR-122miR-133amiR-375 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Denis Delic Claudia Eisele Ramona Schmid Gerd Luippold Eric Mayoux Rolf Grempler |
spellingShingle |
Denis Delic Claudia Eisele Ramona Schmid Gerd Luippold Eric Mayoux Rolf Grempler Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats International Journal of Molecular Sciences ZDF rats hyperinsulinemia diabetes micro-RNA biomarker disease progression miR-122 miR-133a miR-375 |
author_facet |
Denis Delic Claudia Eisele Ramona Schmid Gerd Luippold Eric Mayoux Rolf Grempler |
author_sort |
Denis Delic |
title |
Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats |
title_short |
Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats |
title_full |
Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats |
title_fullStr |
Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats |
title_full_unstemmed |
Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats |
title_sort |
characterization of micro-rna changes during the progression of type 2 diabetes in zucker diabetic fatty rats |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2016-05-01 |
description |
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. |
topic |
ZDF rats hyperinsulinemia diabetes micro-RNA biomarker disease progression miR-122 miR-133a miR-375 |
url |
http://www.mdpi.com/1422-0067/17/5/665 |
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