Glucose-Dependent miR-125b Is a Negative Regulator of β-Cell Function

Research output: Contribution to journalJournal articlepeer-review

Standard

Glucose-Dependent miR-125b Is a Negative Regulator of β-Cell Function. / Cheung, Rebecca; Pizza, Grazia; Chabosseau, Pauline; Rolando, Delphine; Tomas, Alejandra; Burgoyne, Thomas; Wu, Zhiyi; Salowka, Anna; Thapa, Anusha; Macklin, Annabel; Cao, Yufei; Nguyen-Tu, Marie Sophie; Dickerson, Matthew T.; Jacobson, David A.; Marchetti, Piero; Shapiro, James; Piemonti, Lorenzo; de Koning, Eelco; Leclerc, Isabelle; Bouzakri, Karim; Sakamoto, Kei; Smith, David M.; Rutter, Guy A.; Martinez-Sanchez, Aida.

In: Diabetes, Vol. 71, No. 7, 2022, p. 1525-1545.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Cheung, R, Pizza, G, Chabosseau, P, Rolando, D, Tomas, A, Burgoyne, T, Wu, Z, Salowka, A, Thapa, A, Macklin, A, Cao, Y, Nguyen-Tu, MS, Dickerson, MT, Jacobson, DA, Marchetti, P, Shapiro, J, Piemonti, L, de Koning, E, Leclerc, I, Bouzakri, K, Sakamoto, K, Smith, DM, Rutter, GA & Martinez-Sanchez, A 2022, 'Glucose-Dependent miR-125b Is a Negative Regulator of β-Cell Function', Diabetes, vol. 71, no. 7, pp. 1525-1545. https://doi.org/10.2337/db21-0803

APA

Cheung, R., Pizza, G., Chabosseau, P., Rolando, D., Tomas, A., Burgoyne, T., Wu, Z., Salowka, A., Thapa, A., Macklin, A., Cao, Y., Nguyen-Tu, M. S., Dickerson, M. T., Jacobson, D. A., Marchetti, P., Shapiro, J., Piemonti, L., de Koning, E., Leclerc, I., ... Martinez-Sanchez, A. (2022). Glucose-Dependent miR-125b Is a Negative Regulator of β-Cell Function. Diabetes, 71(7), 1525-1545. https://doi.org/10.2337/db21-0803

Vancouver

Cheung R, Pizza G, Chabosseau P, Rolando D, Tomas A, Burgoyne T et al. Glucose-Dependent miR-125b Is a Negative Regulator of β-Cell Function. Diabetes. 2022;71(7):1525-1545. https://doi.org/10.2337/db21-0803

Author

Cheung, Rebecca ; Pizza, Grazia ; Chabosseau, Pauline ; Rolando, Delphine ; Tomas, Alejandra ; Burgoyne, Thomas ; Wu, Zhiyi ; Salowka, Anna ; Thapa, Anusha ; Macklin, Annabel ; Cao, Yufei ; Nguyen-Tu, Marie Sophie ; Dickerson, Matthew T. ; Jacobson, David A. ; Marchetti, Piero ; Shapiro, James ; Piemonti, Lorenzo ; de Koning, Eelco ; Leclerc, Isabelle ; Bouzakri, Karim ; Sakamoto, Kei ; Smith, David M. ; Rutter, Guy A. ; Martinez-Sanchez, Aida. / Glucose-Dependent miR-125b Is a Negative Regulator of β-Cell Function. In: Diabetes. 2022 ; Vol. 71, No. 7. pp. 1525-1545.

Bibtex

@article{f4125d7c324f4087a7e7a4fb2364b13d,
title = "Glucose-Dependent miR-125b Is a Negative Regulator of β-Cell Function",
abstract = "Impaired pancreatic β-cell function and insulin secretion are hallmarks of type 2 diabetes. miRNAs are short, noncoding RNAs that silence gene expression vital for the development and function of β cells. We have previously shown that β cell-specific deletion of the important energy sensor AMP-activated protein kinase (AMPK) results in increased miR-125b-5p levels. Nevertheless, the function of this miRNA in β cells is unclear. We hypothesized that miR-125b-5p expression is regulated by glucose and that this miRNA mediates some of the deleterious effects of hyperglycemia in β cells. Here, we show that islet miR-125b-5p expression is upregulated by glucose in an AMPK-dependent manner and that short-term miR-125b-5p overexpression impairs glucose-stimulated insulin secretion (GSIS) in the mouse insulinoma MIN6 cells and in human islets. An unbiased, high-throughput screen in MIN6 cells identified multiple miR-125b-5p targets, including the transporter of lysosomal hydrolases M6pr and the mitochondrial fission regulator Mtfp1. Inactivation of miR-125b-5p in the human β-cell line EndoCβ-H1 shortened mitochondria and enhanced GSIS, whereas mice overexpressing miR-125b-5p selectively in β cells (MIR125B-Tg) were hyperglycemic and glucose intolerant. MIR125B-Tg β cells contained enlarged lysosomal structures and had reduced insulin content and secretion. Collectively, we identify miR-125b as a glucose-controlled regulator of organelle dynamics that modulates insulin secretion.",
author = "Rebecca Cheung and Grazia Pizza and Pauline Chabosseau and Delphine Rolando and Alejandra Tomas and Thomas Burgoyne and Zhiyi Wu and Anna Salowka and Anusha Thapa and Annabel Macklin and Yufei Cao and Nguyen-Tu, {Marie Sophie} and Dickerson, {Matthew T.} and Jacobson, {David A.} and Piero Marchetti and James Shapiro and Lorenzo Piemonti and {de Koning}, Eelco and Isabelle Leclerc and Karim Bouzakri and Kei Sakamoto and Smith, {David M.} and Rutter, {Guy A.} and Aida Martinez-Sanchez",
note = "Publisher Copyright: {\textcopyright} 2022 by the American Diabetes Association.",
year = "2022",
doi = "10.2337/db21-0803",
language = "English",
volume = "71",
pages = "1525--1545",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "7",

}

RIS

TY - JOUR

T1 - Glucose-Dependent miR-125b Is a Negative Regulator of β-Cell Function

AU - Cheung, Rebecca

AU - Pizza, Grazia

AU - Chabosseau, Pauline

AU - Rolando, Delphine

AU - Tomas, Alejandra

AU - Burgoyne, Thomas

AU - Wu, Zhiyi

AU - Salowka, Anna

AU - Thapa, Anusha

AU - Macklin, Annabel

AU - Cao, Yufei

AU - Nguyen-Tu, Marie Sophie

AU - Dickerson, Matthew T.

AU - Jacobson, David A.

AU - Marchetti, Piero

AU - Shapiro, James

AU - Piemonti, Lorenzo

AU - de Koning, Eelco

AU - Leclerc, Isabelle

AU - Bouzakri, Karim

AU - Sakamoto, Kei

AU - Smith, David M.

AU - Rutter, Guy A.

AU - Martinez-Sanchez, Aida

N1 - Publisher Copyright: © 2022 by the American Diabetes Association.

PY - 2022

Y1 - 2022

N2 - Impaired pancreatic β-cell function and insulin secretion are hallmarks of type 2 diabetes. miRNAs are short, noncoding RNAs that silence gene expression vital for the development and function of β cells. We have previously shown that β cell-specific deletion of the important energy sensor AMP-activated protein kinase (AMPK) results in increased miR-125b-5p levels. Nevertheless, the function of this miRNA in β cells is unclear. We hypothesized that miR-125b-5p expression is regulated by glucose and that this miRNA mediates some of the deleterious effects of hyperglycemia in β cells. Here, we show that islet miR-125b-5p expression is upregulated by glucose in an AMPK-dependent manner and that short-term miR-125b-5p overexpression impairs glucose-stimulated insulin secretion (GSIS) in the mouse insulinoma MIN6 cells and in human islets. An unbiased, high-throughput screen in MIN6 cells identified multiple miR-125b-5p targets, including the transporter of lysosomal hydrolases M6pr and the mitochondrial fission regulator Mtfp1. Inactivation of miR-125b-5p in the human β-cell line EndoCβ-H1 shortened mitochondria and enhanced GSIS, whereas mice overexpressing miR-125b-5p selectively in β cells (MIR125B-Tg) were hyperglycemic and glucose intolerant. MIR125B-Tg β cells contained enlarged lysosomal structures and had reduced insulin content and secretion. Collectively, we identify miR-125b as a glucose-controlled regulator of organelle dynamics that modulates insulin secretion.

AB - Impaired pancreatic β-cell function and insulin secretion are hallmarks of type 2 diabetes. miRNAs are short, noncoding RNAs that silence gene expression vital for the development and function of β cells. We have previously shown that β cell-specific deletion of the important energy sensor AMP-activated protein kinase (AMPK) results in increased miR-125b-5p levels. Nevertheless, the function of this miRNA in β cells is unclear. We hypothesized that miR-125b-5p expression is regulated by glucose and that this miRNA mediates some of the deleterious effects of hyperglycemia in β cells. Here, we show that islet miR-125b-5p expression is upregulated by glucose in an AMPK-dependent manner and that short-term miR-125b-5p overexpression impairs glucose-stimulated insulin secretion (GSIS) in the mouse insulinoma MIN6 cells and in human islets. An unbiased, high-throughput screen in MIN6 cells identified multiple miR-125b-5p targets, including the transporter of lysosomal hydrolases M6pr and the mitochondrial fission regulator Mtfp1. Inactivation of miR-125b-5p in the human β-cell line EndoCβ-H1 shortened mitochondria and enhanced GSIS, whereas mice overexpressing miR-125b-5p selectively in β cells (MIR125B-Tg) were hyperglycemic and glucose intolerant. MIR125B-Tg β cells contained enlarged lysosomal structures and had reduced insulin content and secretion. Collectively, we identify miR-125b as a glucose-controlled regulator of organelle dynamics that modulates insulin secretion.

U2 - 10.2337/db21-0803

DO - 10.2337/db21-0803

M3 - Journal article

C2 - 35476777

AN - SCOPUS:85133102872

VL - 71

SP - 1525

EP - 1545

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 7

ER -

ID: 313707027