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.
Highlights
Type 2 diabetes (T2D) affects 285 million people worldwide (2010), and the numbers are projected to increase substantially in the years to come up to 366 million in 2030 [1,2]
The present study characterizes the micro-RNA changes during natural progression of T2D in chow-fed, aging Zucker diabetic fatty (ZDF) rats from six weeks of age to 17 weeks of age (n = 10)
The present study characterizes the changes in the free circulating level of micro-RNAs in blood during the natural progression of T2D in chow-fed, aging ZDF rats from pre-diabetes over initial hyperinsulinemia to β cell failure and late-stage diabetes
Summary
Type 2 diabetes (T2D) affects 285 million people worldwide (2010), and the numbers are projected to increase substantially in the years to come up to 366 million in 2030 [1,2]. Several effective drugs are available for the treatment of T2D with the generic metformin, sulfonylureas and thiazolidinediones and novel drugs, like Dipeptidyl peptidase-4 inhibitors (DPP-4i), Sodium-dependent glucose transporter inhibitors (SGLT2i), injectable Glucagon-like peptide-1 analogues (GLP-1a) or insulin. Many patients require combination treatment to prevent deterioration of glucose control over the years and later complications of T2D, like diabetic retinopathy or diabetic nephropathy [4]. In order to show the beneficial effects of new treatments for T2D on disease progression, clinical trials need to be performed over a long period of time up to five years of treatment. Better knowledge in understanding the pathophysiological mechanisms will be crucial for designing new strategies to prevent and/or treat the progression of T2D
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