MicroRNAs as regulators of beta-cell function and dysfunction

TY - JOUR

T1 - MicroRNAs as regulators of beta-cell function and dysfunction

AU - Osmai, Mirwais

AU - Osmai, Yama

AU - Bang-Berthelsen, Claus Heiner

AU - Pallesen, Emil Marek Heymans

AU - Vestergaard, Anna Lindeløv

AU - Novotny, Guy Wayne

AU - Pociot, Flemming

AU - Mandrup-Poulsen, Thomas

PY - 2016/5/1

Y1 - 2016/5/1

N2 - In the last decade, there has been an explosion in both the number of and knowledge about miRNAs associated with both type 1 and type 2 diabetes. Even though we are presently in the initial stages of understanding how this novel class of posttranscriptional regulators are involved in diabetes, recent studies have demonstrated that miRNAs are important regulators of the islet transcriptome, controlling apoptosis, differentiation and proliferation, as well as regulating unique islet and beta-cell functions and pathways such as insulin expression, processing and secretion. Furthermore, a large number of miRNAs have been linked to diabetogenic processes induced by elevated levels of glucose, free fatty acids and inflammatory cytokines. Thus, miRNAs are novel therapeutic targets with the potential of protecting the beta-cell, and there is proof of principle that miRNA antagonists, so-called antagomirs, are effective in vivo for other disorders. miRNAs are exported out of cells in exosomes, raising the intriguing possibility of cell-to-cell communication between distant tissues via miRNAs and that miRNAs can be used as biomarkers of beta-cell function, mass and survival. The purpose of this review is to provide a status on how miRNAs control beta-cell function and viability in health and disease.

AB - In the last decade, there has been an explosion in both the number of and knowledge about miRNAs associated with both type 1 and type 2 diabetes. Even though we are presently in the initial stages of understanding how this novel class of posttranscriptional regulators are involved in diabetes, recent studies have demonstrated that miRNAs are important regulators of the islet transcriptome, controlling apoptosis, differentiation and proliferation, as well as regulating unique islet and beta-cell functions and pathways such as insulin expression, processing and secretion. Furthermore, a large number of miRNAs have been linked to diabetogenic processes induced by elevated levels of glucose, free fatty acids and inflammatory cytokines. Thus, miRNAs are novel therapeutic targets with the potential of protecting the beta-cell, and there is proof of principle that miRNA antagonists, so-called antagomirs, are effective in vivo for other disorders. miRNAs are exported out of cells in exosomes, raising the intriguing possibility of cell-to-cell communication between distant tissues via miRNAs and that miRNAs can be used as biomarkers of beta-cell function, mass and survival. The purpose of this review is to provide a status on how miRNAs control beta-cell function and viability in health and disease.

KW - Faculty of Health and Medical Sciences

KW - miRNA

KW - diabetes

KW - apoptosis

KW - Islets of Langerhans

KW - Insulin

KW - beta cell

U2 - 10.1002/dmrr.2719

DO - 10.1002/dmrr.2719

M3 - Journal article

C2 - 26418758

SN - 1520-7552

VL - 32

SP - 334

EP - 349

JO - Diabetes - Metabolism: Research and Reviews (Print Edition)

JF - Diabetes - Metabolism: Research and Reviews (Print Edition)

IS - 4

ER -