The Lin28/let-7 axis regulates glucose metabolism.
Details
Serval ID
serval:BIB_FB89C9093637
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Lin28/let-7 axis regulates glucose metabolism.
Journal
Cell
Working group(s)
DIAGRAM Consortium, MAGIC Investigators
Contributor(s)
Voight BF., Scott LJ., Steinthorsdottir V., Morris AP., Dina C., Welch RP., Zeggini E., Huth C., Aulchenko YS., Thorleifsson G., McCulloch LJ., Ferreira T., Grallert H., Amin N., Wu G., Willer CJ., Raychaudhuri S., McCarroll SA., Langenberg C., Hofmann OM., Dupuis J., Qi L., Segrè AV., van Hoek M., Navarro P., Ardlie K., Balkau B., Benediktsson R., Bennett AJ., Blagieva R., Boerwinkle E., Bonnycastle LL., Boström KB., Bravenboer B., Bumpstead S., Burtt£££Noël P£££ NP. , Charpentier G., Chines PS., Cornelis M., Couper DJ., Crawford G., Doney AS., Elliott KS., Elliott AL., Erdos MR., Fox CS., Franklin CS., Ganser M., Gieger C., Grarup N., Green T., Griffin S., Groves CJ., Guiducci C., Hadjadj S., Hassanali N., Herder C., Isomaa B., Jackson AU., Johnson PR., Jørgensen T., Kao WH., Klopp N., Kong A., Kraft P., Kuusisto J., Lauritzen T., Li M., Lieverse A., Lindgren CM., Lyssenko V., Marre M., Meitinger T., Midthjell K., Morken MA., Narisu N., Nilsson P., Owen KR., Payne F., Perry JR., Petersen AK., Platou C., Proença C., Prokopenko I., Rathmann W., Rayner NW., Robertson NR., Rocheleau G., Roden M., Sampson MJ., Saxena R., Shields BM., Shrader P., Sigurdsson G., Sparsø T., Strassburger K., Stringham HM., Sun Q., Swift AJ., Thorand B., Tichet J., Tuomi T., van Dam RM. , van Haeften TW. , van Herpt T., van Vliet-Ostaptchouk JV. , Walters GB., Weedon MN., Wijmenga C., Witteman J., Bergman RN., Cauchi S., Collins FS., Gloyn AL., Gyllensten U., Hansen T., Hide WA., Hitman GA., Hofman A., Hunter DJ., Hveem K., Laakso M., Mohlke KL., Morris AD., Palmer CN., Pramstaller PP., Rudan I., Sijbrands E., Stein LD., Tuomilehto J., Uitterlinden A., Walker M., Wareham NJ., Watanabe RM., Abecasis GR., Boehm BO., Campbell H., Daly MJ., Hattersley AT., Hu FB., Meigs JB., Pankow JS., Pedersen O., Wichmann HE., Barroso£££Inês£££ I. , Florez JC., Frayling TM., Groop L., Sladek R., Thorsteinsdottir U., Wilson JF., Illig T., Froguel P., van Duijn CM. , Stefansson K., Altshuler D., Boehnke M., McCarthy MI., Dupuis J., Langenberg C., Prokopenko I., Saxena R., Soranzo N., Jackson AU., Wheeler E., Glazer NL., Bouatia-Naji N., Gloyn AL., Lindgren CM., Mägi R., Morris AP., Randall J., Johnson T., Elliott P., Rybin D., Thorleifsson G., Steinthorsdottir V., Henneman P., Grallert H., Dehghan A., Hottenga JJ., Franklin CS., Navarro P., Song K., Goel A., Perry JR., Egan JM., Lajunen T., Grarup N., Sparsø T., Doney A., Voight BF., Stringham HM., Li M., Kanoni S., Shrader P., Cavalcanti-Proença C., Kumari M., Qi L., Timpson NJ., Gieger C., Zabena C., Rocheleau G., Ingelsson E., An P., O'Connell J., Luan£££Jian'an£££ J. , Elliott A., McCarroll SA., Payne F., Roccasecca RM., Pattou F., Sethupathy P., Ardlie K., Ariyurek Y., Balkau B., Barter P., Beilby JP., Ben-Shlomo Y., Benediktsson R., Bennett AJ., Bergmann S., Bochud M., Boerwinkle E., Bonnefond A., Bonnycastle LL., Borch-Johnsen K., Böttcher Y., Brunner E., Bumpstead SJ., Charpentier G., Chen YD., Chines P., Clarke R., Coin LJ., Cooper MN., Cornelis M., Crawford G., Crisponi L., Day IN., de Geus EJ. , Delplanque J., Dina C., Erdos MR., Fedson AC., Fischer-Rosinsky A., Forouhi NG., Fox CS., Frants R., Franzosi MG., Galan P., Goodarzi MO., Graessler J., Groves CJ., Grundy S., Gwilliam R., Gyllensten U., Hadjadj S., Hallmans G., Hammond N., Han X., Hartikainen AL., Hassanali N., Hayward C., Heath SC., Hercberg S., Herder C., Hicks AA., Hillman DR., Hingorani AD., Hofman A., Hui J., Hung J., Isomaa B., Johnson PR., Jørgensen T., Jula A., Kaakinen M., Kaprio J., Kesaniemi YA., Kivimaki M., Knight B., Koskinen S., Kovacs P., Kyvik KO., Lathrop GM., Lawlor DA., Le Bacquer O., Lecoeur C., Li Y., Lyssenko V., Mahley R., Mangino M., Manning AK., Martínez-Larrad£££María Teresa£££ MT. , McAteer JB., McCulloch LJ., McPherson R., Meisinger C., Melzer D., Meyre D., Mitchell BD., Morken MA., Mukherjee S., Naitza S., Narisu N., Neville MJ., Oostra BA., Orrù M., Pakyz R., Palmer CN., Paolisso G., Pattaro C., Pearson D., Peden JF., Pedersen NL., Perola M., Pfeiffer AF., Pichler I., Polasek O., Posthuma D., Potter SC., Pouta A., Province MA., Psaty BM., Rathmann W., Rayner NW., Rice K., Ripatti S., Rivadeneira F., Roden M., Rolandsson O., Sandbaek A., Sandhu M., Sanna S., Sayer AA., Scheet P., Scott LJ., Seedorf U., Sharp SJ., Shields B., Sigurðsson G., Sijbrands EJ., Silveira A., Simpson L., Singleton A., Smith NL., Sovio U., Swift A., Syddall H., Syvänen AC., Tanaka T., Thorand B., Tichet J., Tönjes A., Tuomi T., Uitterlinden AG., van Dijk KW. , van Hoek M., Varma D., Visvikis-Siest S., Vitart V., Vogelzangs N., Waeber G., Wagner PJ., Walley A., Walters GB., Ward KL., Watkins H., Weedon MN., Wild SH., Willemsen G., Witteman JC., Yarnell JW., Zeggini E., Zelenika D., Zethelius B., Zhai G., Zhao JH., Zillikens MC., Borecki IB., Loos RJ., Meneton P., Magnusson PK., Nathan DM., Williams GH., Hattersley AT., Silander K., Salomaa V., Smith GD., Bornstein SR., Schwarz P., Spranger J., Karpe F., Shuldiner AR., Cooper C., Dedoussis GV., Serrano-Ríos M., Morris AD., Lind L., Palmer LJ., Hu FB., Franks PW., Ebrahim S., Marmot M., Kao WH., Pankow JS., Sampson MJ., Kuusisto J., Laakso M., Hansen T., Pedersen O., Pramstaller PP., Wichmann HE., Illig T., Rudan I., Wright AF., Stumvoll M., Campbell H., Wilson JF., Hamsten A., Bergman RN., Buchanan TA., Collins FS., Mohlke KL., Tuomilehto J., Valle TT., Altshuler D., Rotter JI., Siscovick DS., Penninx BW., Boomsma DI., Deloukas P., Spector TD., Frayling TM., Ferrucci L., Kong A., Thorsteinsdottir U., Stefansson K., van Duijn CM. , Aulchenko YS., Cao A., Scuteri A., Schlessinger D., Uda M., Ruokonen A., Jarvelin MR., Waterworth DM., Vollenweider P., Peltonen L., Mooser V., Abecasis GR., Wareham NJ., Sladek R., Froguel P., Watanabe RM., Meigs JB., Groop L., Boehnke M., McCarthy MI., Florez JC., Barroso£££Inês£££ I.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
2011
Volume
147
Number
1
Pages
81-94
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism.
Keywords
Animals, Diabetes Mellitus, Type 2/metabolism, Gene Expression Regulation, Genome-Wide Association Study, Glucose/metabolism, Humans, Insulin Resistance, Mice, Mice, Knockout, Mice, Transgenic, MicroRNAs/genetics, MicroRNAs/metabolism, Obesity/genetics, Obesity/metabolism, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2011 12:36
Last modification date
20/08/2019 17:26
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