title: Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats.
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.
authors.affiliation: Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH &amp; Co. KG, 88397 Biberach an der Riss, Germany. denis.delic@boehringer-ingelheim.com.
authors.forename: Denis
authors.initials: D
authors.lastname: Delic
authors.affiliation: Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH &amp; Co. KG, 88397 Biberach an der Riss, Germany. claudia.eisele@boehringer-ingelheim.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Eisele
authors.affiliation: Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH &amp; Co. KG, 88397 Biberach an der Riss, Germany. ramona.schmid@boehringer-ingelheim.com.
authors.forename: Ramona
authors.initials: R
authors.lastname: Schmid
authors.affiliation: Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH &amp; Co. KG, 88397 Biberach an der Riss, Germany. gerd.luippold@boehringer-ingelheim.com.
authors.forename: Gerd
authors.initials: G
authors.lastname: Luippold
authors.affiliation: Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH &amp; Co. KG, 88397 Biberach an der Riss, Germany. eric.mayoux@boehringer-ingelheim.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Mayoux
authors.affiliation: Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH &amp; Co. KG, 88397 Biberach an der Riss, Germany. rolf.grempler@boehringer-ingelheim.com.
authors.forename: Rolf
authors.initials: R
authors.lastname: Grempler
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D015415:Biomarkers; D007328:Insulin; D035683:MicroRNAs
keywords: ZDF rats; biomarker; diabetes; disease progression; hyperinsulinemia; miR-122; miR-133a; miR-375; micro-RNA