MiR-184 expression is regulated by AMPK in pancreatic islets

Aida Martinez-Sanchez; Marie-Sophie Nguyen-Tu; Ines Cebola; Arash Yavari; Piero Marchetti; Lorenzo Piemonti; Eelco de Koning; A M James Shapiro; Paul Johnson; Kei Sakamoto; David M Smith; Isabelle Leclerc; Houman Ashrafian; Jorge Ferrer; Guy A Rutter

doi:10.1096/fj.201701100R

MiR-184 expression is regulated by AMPK in pancreatic islets

Aida Martinez-Sanchez, Marie-Sophie Nguyen-Tu, Ines Cebola, Arash Yavari, Piero Marchetti, Lorenzo Piemonti, Eelco de Koning, A M James Shapiro, Paul Johnson, Kei Sakamoto, David M Smith, Isabelle Leclerc, Houman Ashrafian, Jorge Ferrer, Guy A Rutter

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

38 Citations (Scopus)

Abstract

AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β-cells. We identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β-cell function and identity. The most down-regulated miRNA was miR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity are central for the regulation of miR-184 and other miRNAs in islets and provide a link between energy status and gene expression in β-cells.-Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR-184 expression is regulated by AMPK in pancreatic islets.

Original language	English
Journal	FASEB Journal
DOIs	https://doi.org/10.1096/fj.201701100R
Publication status	E-pub ahead of print - 21 Dec 2017

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Journal Article

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10.1096/fj.201701100R

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Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., & Rutter, G. A. (2017). MiR-184 expression is regulated by AMPK in pancreatic islets. FASEB Journal. Advance online publication. https://doi.org/10.1096/fj.201701100R

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title = "MiR-184 expression is regulated by AMPK in pancreatic islets",

abstract = "AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β-cells. We identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β-cell function and identity. The most down-regulated miRNA was miR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity are central for the regulation of miR-184 and other miRNAs in islets and provide a link between energy status and gene expression in β-cells.-Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR-184 expression is regulated by AMPK in pancreatic islets.",

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author = "Aida Martinez-Sanchez and Marie-Sophie Nguyen-Tu and Ines Cebola and Arash Yavari and Piero Marchetti and Lorenzo Piemonti and {de Koning}, Eelco and Shapiro, {A M James} and Paul Johnson and Kei Sakamoto and Smith, {David M} and Isabelle Leclerc and Houman Ashrafian and Jorge Ferrer and Rutter, {Guy A}",

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T1 - MiR-184 expression is regulated by AMPK in pancreatic islets

AU - Martinez-Sanchez, Aida

AU - Nguyen-Tu, Marie-Sophie

AU - Cebola, Ines

AU - Yavari, Arash

AU - Marchetti, Piero

AU - Piemonti, Lorenzo

AU - de Koning, Eelco

AU - Shapiro, A M James

AU - Johnson, Paul

AU - Sakamoto, Kei

AU - Smith, David M

AU - Leclerc, Isabelle

AU - Ashrafian, Houman

AU - Ferrer, Jorge

AU - Rutter, Guy A

N1 - © FASEB.

PY - 2017/12/21

Y1 - 2017/12/21

N2 - AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β-cells. We identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β-cell function and identity. The most down-regulated miRNA was miR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity are central for the regulation of miR-184 and other miRNAs in islets and provide a link between energy status and gene expression in β-cells.-Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR-184 expression is regulated by AMPK in pancreatic islets.

AB - AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β-cells. We identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β-cell function and identity. The most down-regulated miRNA was miR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity are central for the regulation of miR-184 and other miRNAs in islets and provide a link between energy status and gene expression in β-cells.-Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR-184 expression is regulated by AMPK in pancreatic islets.

KW - Journal Article

U2 - 10.1096/fj.201701100R

DO - 10.1096/fj.201701100R

M3 - Article

C2 - 29269398

SN - 0892-6638

JO - FASEB Journal

JF - FASEB Journal

ER -

MiR-184 expression is regulated by AMPK in pancreatic islets

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