MicroRNA Networks in Pancreatic Islet Cells: Normal Function and Type 2 Diabetes

Author:

Eliasson Lena1ORCID,Esguerra Jonathan L.S.1

Affiliation:

1. Islet Cell Exocytosis, Lund University Diabetes Centre; Department of Clinical Sciences Malmö, Lund University; and Clinical Research Centre, Skåne University Hospital, Malmö, Sweden

Abstract

Impaired insulin secretion from the pancreatic β-cells is central in the pathogenesis of type 2 diabetes (T2D), and microRNAs (miRNAs) are fundamental regulatory factors in this process. Differential expression of miRNAs contributes to β-cell adaptation to compensate for increased insulin resistance, but deregulation of miRNA expression can also directly cause β-cell impairment during the development of T2D. miRNAs are small noncoding RNAs that posttranscriptionally reduce gene expression through translational inhibition or mRNA destabilization. The nature of miRNA targeting implies the presence of complex and large miRNA–mRNA regulatory networks in every cell, including the insulin-secreting β-cell. Here we exemplify one such network using our own data on differential miRNA expression in the islets of T2D Goto-Kakizaki rat model. Several biological processes are influenced by multiple miRNAs in the β-cell, but so far most studies have focused on dissecting the mechanism of action of individual miRNAs. In this Perspective we present key islet miRNA families involved in T2D pathogenesis including miR-200, miR-7, miR-184, miR-212/miR-132, and miR-130a/b/miR-152. Finally, we highlight four challenges and opportunities within islet miRNA research, ending with a discussion on how miRNAs can be utilized as therapeutic targets contributing to personalized T2D treatment strategies.

Funder

Swedish Foundation for Strategic Research

Swedish Research Council

Region Skåne-ALF

Swedish Diabetes Foundation

Diabetes Wellness Network Sweden

Albert Påhlsson Foundation

Crafoord Foundation

Byggmästare Olle Engqvist Foundation

Syskonen Svenssons Fond

European Union’s Horizon 2020 Research and Innovation Programme

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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