Argonaute2 mediates compensatory expansion of the pancreatic β cell

Sudhir G Tattikota; Thomas Rathjen; Sarah J McAnulty; Hans-Hermann Wessels; Ildem Akerman; Martijn van de Bunt; Jean Hausser; Jonathan L S Esguerra; Anne Musahl; Amit K Pandey; Xintian You; Wei Chen; Pedro L Herrera; Paul R Johnson; Donal O'Carroll; Lena Eliasson; Mihaela Zavolan; Anna L Gloyn; Jorge Ferrer; Ruby Shalom-Feuerstein; Daniel Aberdam; Matthew N Poy

doi:10.1016/j.cmet.2013.11.015

Argonaute2 mediates compensatory expansion of the pancreatic β cell

Sudhir G Tattikota, Thomas Rathjen, Sarah J McAnulty, Hans-Hermann Wessels, Ildem Akerman, Martijn van de Bunt, Jean Hausser, Jonathan L S Esguerra, Anne Musahl, Amit K Pandey, Xintian You, Wei Chen, Pedro L Herrera, Paul R Johnson, Donal O'Carroll, Lena Eliasson, Mihaela Zavolan, Anna L Gloyn, Jorge Ferrer, Ruby Shalom-FeuersteinDaniel Aberdam, Matthew N Poy

Metabolism and Systems Research

Research output: Contribution to journal › Article › peer-review

95 Citations (Scopus)

Abstract

Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.

Original language	English
Pages (from-to)	122-34
Number of pages	13
Journal	Cell Metabolism
Volume	19
Issue number	1
Early online date	19 Dec 2013
DOIs	https://doi.org/10.1016/j.cmet.2013.11.015
Publication status	Published - 7 Jan 2014

Keywords

Animals
Argonaute Proteins
Cell Proliferation
Diet, Ketogenic
Gene Expression Regulation
Gene Silencing
Humans
Insulin Resistance
Insulin-Secreting Cells
Mice
Mice, Obese
MicroRNAs
Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmet.2013.11.015Licence: Creative Commons: Attribution (CC BY)

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Tattikota, S. G., Rathjen, T., McAnulty, S. J., Wessels, H-H., Akerman, I., van de Bunt, M., Hausser, J., Esguerra, J. L. S., Musahl, A., Pandey, A. K., You, X., Chen, W., Herrera, P. L., Johnson, P. R., O'Carroll, D., Eliasson, L., Zavolan, M., Gloyn, A. L., Ferrer, J., ... Poy, M. N. (2014). Argonaute2 mediates compensatory expansion of the pancreatic β cell. Cell Metabolism, 19(1), 122-34. Advance online publication. https://doi.org/10.1016/j.cmet.2013.11.015

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title = "Argonaute2 mediates compensatory expansion of the pancreatic β cell",

abstract = "Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.",

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doi = "10.1016/j.cmet.2013.11.015",

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Tattikota, SG, Rathjen, T, McAnulty, SJ, Wessels, H-H, Akerman, I, van de Bunt, M, Hausser, J, Esguerra, JLS, Musahl, A, Pandey, AK, You, X, Chen, W, Herrera, PL, Johnson, PR, O'Carroll, D, Eliasson, L, Zavolan, M, Gloyn, AL, Ferrer, J, Shalom-Feuerstein, R, Aberdam, D & Poy, MN 2014, 'Argonaute2 mediates compensatory expansion of the pancreatic β cell', Cell Metabolism, vol. 19, no. 1, pp. 122-34. https://doi.org/10.1016/j.cmet.2013.11.015

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T1 - Argonaute2 mediates compensatory expansion of the pancreatic β cell

AU - Tattikota, Sudhir G

AU - Rathjen, Thomas

AU - McAnulty, Sarah J

AU - Wessels, Hans-Hermann

AU - Akerman, Ildem

AU - van de Bunt, Martijn

AU - Hausser, Jean

AU - Esguerra, Jonathan L S

AU - Musahl, Anne

AU - Pandey, Amit K

AU - You, Xintian

AU - Chen, Wei

AU - Herrera, Pedro L

AU - Johnson, Paul R

AU - O'Carroll, Donal

AU - Eliasson, Lena

AU - Zavolan, Mihaela

AU - Gloyn, Anna L

AU - Ferrer, Jorge

AU - Shalom-Feuerstein, Ruby

AU - Aberdam, Daniel

AU - Poy, Matthew N

PY - 2014/1/7

Y1 - 2014/1/7

N2 - Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.

AB - Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.

KW - Animals

KW - Argonaute Proteins

KW - Cell Proliferation

KW - Diet, Ketogenic

KW - Gene Expression Regulation

KW - Gene Silencing

KW - Humans

KW - Insulin Resistance

KW - Insulin-Secreting Cells

KW - Mice

KW - Mice, Obese

KW - MicroRNAs

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.cmet.2013.11.015

DO - 10.1016/j.cmet.2013.11.015

M3 - Article

C2 - 24361012

SN - 1550-4131

VL - 19

SP - 122

EP - 134

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -

Argonaute2 mediates compensatory expansion of the pancreatic β cell

Abstract

Keywords

UN SDGs

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