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 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 Poy

Research output: Contribution to journal › Article

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 (US)
Pages (from-to)	122-134
Number of pages	13
Journal	Cell Metabolism
Volume	19
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2013.11.015
State	Published - Jan 7 2014
Externally published	Yes

Fingerprint

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

Cite this

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. (2014). Argonaute2 mediates compensatory expansion of the pancreatic β cell. Cell Metabolism, 19(1), 122-134. https://doi.org/10.1016/j.cmet.2013.11.015

Argonaute2 mediates compensatory expansion of the pancreatic β cell. / Tattikota, Sudhir G.; Rathjen, Thomas; McAnulty, Sarah J.; Wessels, Hans Hermann; Akerman, Ildem; Van De Bunt, Martijn; Hausser, Jean; Esguerra, Jonathan L.S.; Musahl, Anne; Pandey, Amit K.; You, Xintian; Chen, Wei; Herrera, Pedro L.; Johnson, Paul R.; O'Carroll, Donal; Eliasson, Lena; Zavolan, Mihaela; Gloyn, Anna L.; Ferrer, Jorge; Shalom-Feuerstein, Ruby; Aberdam, Daniel; Poy, Matthew.

In: Cell Metabolism, Vol. 19, No. 1, 07.01.2014, p. 122-134.

Research output: Contribution to journal › Article

Tattikota, SG, Rathjen, T, McAnulty, SJ, Wessels, HH, 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, M 2014, 'Argonaute2 mediates compensatory expansion of the pancreatic β cell', Cell Metabolism, vol. 19, no. 1, pp. 122-134. https://doi.org/10.1016/j.cmet.2013.11.015

Tattikota, Sudhir G. ; Rathjen, Thomas ; McAnulty, Sarah J. ; Wessels, Hans Hermann ; Akerman, Ildem ; Van De Bunt, Martijn ; Hausser, Jean ; Esguerra, Jonathan L.S. ; Musahl, Anne ; Pandey, Amit K. ; You, Xintian ; Chen, Wei ; Herrera, Pedro L. ; Johnson, Paul R. ; O'Carroll, Donal ; Eliasson, Lena ; Zavolan, Mihaela ; Gloyn, Anna L. ; Ferrer, Jorge ; Shalom-Feuerstein, Ruby ; Aberdam, Daniel ; Poy, Matthew. / Argonaute2 mediates compensatory expansion of the pancreatic β cell. In: Cell Metabolism. 2014 ; Vol. 19, No. 1. pp. 122-134.

@article{79484de88f2048e8bbb9bb38e141556e,

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.",

author = "Tattikota, {Sudhir G.} and Thomas Rathjen and McAnulty, {Sarah J.} and Wessels, {Hans Hermann} and Ildem Akerman and {Van De Bunt}, Martijn and Jean Hausser and Esguerra, {Jonathan L.S.} and Anne Musahl and Pandey, {Amit K.} and Xintian You and Wei Chen and Herrera, {Pedro L.} and Johnson, {Paul R.} and Donal O'Carroll and Lena Eliasson and Mihaela Zavolan and Gloyn, {Anna L.} and Jorge Ferrer and Ruby Shalom-Feuerstein and Daniel Aberdam and Matthew Poy",

year = "2014",

month = jan

day = "7",

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

language = "English (US)",

volume = "19",

pages = "122--134",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

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

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.

UR - http://www.scopus.com/inward/record.url?scp=84891867862&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891867862&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2013.11.015

DO - 10.1016/j.cmet.2013.11.015

M3 - Article

C2 - 24361012

AN - SCOPUS:84891867862

VL - 19

SP - 122

EP - 134

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 1

ER -

Access to Document

10.1016/j.cmet.2013.11.015