Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-019-04937-x REVIEW Circular RNAs in β‑cell function and type 2 diabetes‑related complications: a potential diagnostic and therapeutic approach Hassan Ghasemi 1  · Zolfaghar Sabati 2  · Hamid Ghaedi 3  · Zaker Salehi 4  · Behnam Alipoor 5 Received: 10 April 2019 / Accepted: 20 June 2019 © Springer Nature B.V. 2019 Abstract Recent investigations have indicated that altered expression of non-coding RNAs (ncRNAs) could be associated with human diseases such as type 2 diabetes (T2D). Circular RNAs (circRNAs) are a new discovered class of ncRNAs with unique structural characteristics that involved in several molecular and cellular functions. Exploring of the circulating circRNAs as a reliable non-invasive biomarker for monitoring and diagnosing of human diseases has grown signifcantly. However, the molecular functions and clinical relevance of circRNAs are not yet well clarifed in T2D. Accordingly, in this review, the involvement of circRNAs in the β-cell function and T2D-related complications is highlighted. The study also shed light on the possibility of using circRNAs as a biomarker for T2D diagnosis. Keywords Non-coding RNAs · Circular RNAs · Complications · Biomarkers · Type 2 diabetes Introduction Diabetes mellitus (DM) refers to a group of metabolic disor- ders characterized by hyperglycemia and defect in metabo- lism of macromolecules [1]. According to the international diabetes federation (IDF) reports, about 415 million people sufered from diabetes worldwide in 2017, and this number will rise to 645 million people by 2040 [2, 3]. The etiology of DM varies from the defect in insulin production to defect in response to insulin or both [4]. Type 2 diabetes (T2D) is the most common form of diabetes that mainly develops in adults [5, 6]. T2D starts with postprandial hyperglycemia and insulin resistance followed by the compensatory response of pancreatic β-cells for insulin production, which in turn, lead to decreased β-cell mass [4]. Therefore, it can be concluded that T2D is a combination of insulin resistance and insulin defciency conditions. T2D is associated with several complications that mainly include: hyperosmolar coma, nephropathy, neuropathy, retinopathy, and cardio- vascular disease [7]. Therefore, this metabolic disorder is one of the main factors involved in mortality and morbidity worldwide, and out of the 56.4 million deaths in 2015, about 1.6 million were due to T2D [8]. Since T2D develops as a result of the interaction between genes and environment [9], investigation of gene regulating factors is among the issues of interest to researchers. It is documented that the majority of the mammalian genome is transcribed to the non-coding RNAs (ncRNAs) that play an important role in the regulation of gene expres- sion [10]. Usually, ncRNAs are categorized according to their size into two major groups: long non-coding RNAs (lncRNAs, length > 200 bp) and small non-coding RNAs (small ncRNA, length < 200 bp) [11, 12]. lncRNAs can be also categorized by their structure, function and genomic location. Structurally, lncRNAs are divided into linear RNAs and circular RNAs (CircRNAs). Furthermore, small ncRNA are also composed of two groups that involved in translation, transcription and gene regulation (Fig. 1) [13, 14]. An increasing number of experimental investigations * Behnam Alipoor behnam.alipour@yums.ac.ir 1 Department of Clinical Biochemistry, Abadan Faculty of Medical Sciences, Abadan, Iran 2 Student Research Committee, Abadan Faculty of Medical Sciences, Abadan, Iran 3 Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 Department of Radiation Sciences, Yasuj University of Medical Sciences, Yasuj, Iran 5 Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran