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@article{Cheung:2021:10.1101/2021.05.17.444559,
author = {Cheung, R and Pizza, G and Chabosseau, P and Rolando, D and Tomas, A and Burgoyne, T and Salowka, A and Macklin, A and Cao, Y and Nguyen-Tu, M-S and Marchetti, P and Shapiro, J and Piemonti, L and de, Koning E and Leclerc, I and Sakamoto, K and Smith, DM and Rutter, GA and Martinez-Sanchez, A},
doi = {10.1101/2021.05.17.444559},
journal = {BioRxiv},
title = {Glucose-dependent miR-125b is a negative regulator of β-cell function},
url = {http://dx.doi.org/10.1101/2021.05.17.444559},
year = {2021}
}

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TY  - JOUR
AB  - <jats:title>SUMMARY</jats:title><jats:p>Impaired pancreatic β-cell function and insulin secretion are hallmarks of type 2 diabetes. MicroRNAs are short non-coding RNAs that silence gene expression, vital for the development and function of β-cells. MiR-125b-5p (miR-125b), a highly conserved miRNA, is abundant in β-cells, though its role in these cells is unclear. Here we show that miR-125b levels in human islets correlate with body mass index (BMI), and its expression is regulated by glucose in an AMP-activated protein kinase-dependent manner. An unbiased high-throughput screen identified multiple miR-125b targets, including the transporter of lysosomal hydrolases <jats:italic>M6pr</jats:italic> and the mitochondrial fission regulator <jats:italic>Mtfp1</jats:italic>. Inactivation of miR-125b in human β-cells shortened mitochondria and enhanced glucose-stimulated insulin secretion, whilst mice over-expressing miR-125b selectively in β-cells were glucose intolerant. β-cells from these animals contained enlarged lysosomal structures and showed reduced insulin content and secretion. Thus, we identify miR125b as a glucose-controlled regulator of organelle dynamics that modulates insulin secretion.</jats:p><jats:sec id="s1"><jats:title>Highlights</jats:title><jats:list list-type="bullet"><jats:list-item><jats:p>Islet miR-125b correlates with BMI and is regulated by glucose via AMP-activated protein kinase in β-cells</jats:p></jats:list-item><jats:list-item><jats:p>miR-125b targets dozens of genes including several involved in the regulation of mitochondrial (<jats:italic>Mtfp1</jats:italic>) and lysosomal (<jats:italic>M6pr</jats:italic>) morphology or function</jats:p></jats:list-item><jats:list-item><jats:p>Deletion of miR-125b results in shorter mitochondria an
AU  - Cheung,R
AU  - Pizza,G
AU  - Chabosseau,P
AU  - Rolando,D
AU  - Tomas,A
AU  - Burgoyne,T
AU  - Salowka,A
AU  - Macklin,A
AU  - Cao,Y
AU  - Nguyen-Tu,M-S
AU  - Marchetti,P
AU  - Shapiro,J
AU  - Piemonti,L
AU  - de,Koning E
AU  - Leclerc,I
AU  - Sakamoto,K
AU  - Smith,DM
AU  - Rutter,GA
AU  - Martinez-Sanchez,A
DO  - 10.1101/2021.05.17.444559
PY  - 2021///
TI  - Glucose-dependent miR-125b is a negative regulator of β-cell function
T2  - BioRxiv
UR  - http://dx.doi.org/10.1101/2021.05.17.444559
ER  -

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