Eintrag weiter verarbeiten
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells
Gespeichert in:
| Zeitschriftentitel: | Diabetes |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Diabetes, 57, 2008, 10, S. 2708-2717 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Diabetes Association
|
| Schlagwörter: |
| author_facet |
El Ouaamari, Abdelfattah Baroukh, Nadine Martens, Geert A. Lebrun, Patricia Pipeleers, Daniel van Obberghen, Emmanuel El Ouaamari, Abdelfattah Baroukh, Nadine Martens, Geert A. Lebrun, Patricia Pipeleers, Daniel van Obberghen, Emmanuel |
|---|---|
| author |
El Ouaamari, Abdelfattah Baroukh, Nadine Martens, Geert A. Lebrun, Patricia Pipeleers, Daniel van Obberghen, Emmanuel |
| spellingShingle |
El Ouaamari, Abdelfattah Baroukh, Nadine Martens, Geert A. Lebrun, Patricia Pipeleers, Daniel van Obberghen, Emmanuel Diabetes miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells Endocrinology, Diabetes and Metabolism Internal Medicine |
| author_sort |
el ouaamari, abdelfattah |
| spelling |
El Ouaamari, Abdelfattah Baroukh, Nadine Martens, Geert A. Lebrun, Patricia Pipeleers, Daniel van Obberghen, Emmanuel 0012-1797 1939-327X American Diabetes Association Endocrinology, Diabetes and Metabolism Internal Medicine http://dx.doi.org/10.2337/db07-1614 <jats:p>OBJECTIVE—MicroRNAs are short, noncoding RNAs that regulate gene expression. We hypothesized that the phosphatidylinositol 3-kinase (PI 3-kinase) cascade known to be important in β-cell physiology could be regulated by microRNAs. Here, we focused on the pancreas-specific miR-375 as a potential regulator of its predicted target 3′-phosphoinositide–dependent protein kinase-1 (PDK1), and we analyzed its implication in the response of insulin-producing cells to elevation of glucose levels.</jats:p> <jats:p>RESEARCH DESIGN AND METHODS—We used insulinoma-1E cells to analyze the effects of miR-375 on PDK1 protein level and downstream signaling using Western blotting, glucose-induced insulin gene expression using quantitative RT-PCR, and DNA synthesis by measuring thymidine incorporation. Moreover, we analyzed the effect of glucose on miR-375 expression in both INS-1E cells and primary rat islets. Finally, miR-375 expression in isolated islets was analyzed in diabetic Goto-Kakizaki (GK) rats.</jats:p> <jats:p>RESULTS—We found that miR-375 directly targets PDK1 and reduces its protein level, resulting in decreased glucose-stimulatory action on insulin gene expression and DNA synthesis. Furthermore, glucose leads to a decrease in miR-375 precursor level and a concomitant increase in PDK1 protein. Importantly, regulation of miR-375 expression by glucose occurs in primary rat islets as well. Finally, miR-375 expression was found to be decreased in fed diabetic GK rat islets.</jats:p> <jats:p>CONCLUSIONS—Our findings provide evidence for a role of a pancreatic-specific microRNA, miR-375, in the regulation of PDK1, a key molecule in PI 3-kinase signaling in pancreatic β-cells. The effects of glucose on miR-375 are compatible with the idea that miR-375 is involved in glucose regulation of insulin gene expression and β-cell growth.</jats:p> miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells Diabetes |
| doi_str_mv |
10.2337/db07-1614 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMjMzNy9kYjA3LTE2MTQ |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMjMzNy9kYjA3LTE2MTQ |
| institution |
DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 |
| imprint |
American Diabetes Association, 2008 |
| imprint_str_mv |
American Diabetes Association, 2008 |
| issn |
0012-1797 1939-327X |
| issn_str_mv |
0012-1797 1939-327X |
| language |
English |
| mega_collection |
American Diabetes Association (CrossRef) |
| match_str |
elouaamari2008mir375targets3phosphoinositidedependentproteinkinase1andregulatesglucoseinducedbiologicalresponsesinpancreaticbcells |
| publishDateSort |
2008 |
| publisher |
American Diabetes Association |
| recordtype |
ai |
| record_format |
ai |
| series |
Diabetes |
| source_id |
49 |
| title |
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_unstemmed |
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_full |
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_fullStr |
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_full_unstemmed |
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_short |
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_sort |
mir-375 targets 3′-phosphoinositide–dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic β-cells |
| topic |
Endocrinology, Diabetes and Metabolism Internal Medicine |
| url |
http://dx.doi.org/10.2337/db07-1614 |
| publishDate |
2008 |
| physical |
2708-2717 |
| description |
<jats:p>OBJECTIVE—MicroRNAs are short, noncoding RNAs that regulate gene expression. We hypothesized that the phosphatidylinositol 3-kinase (PI 3-kinase) cascade known to be important in β-cell physiology could be regulated by microRNAs. Here, we focused on the pancreas-specific miR-375 as a potential regulator of its predicted target 3′-phosphoinositide–dependent protein kinase-1 (PDK1), and we analyzed its implication in the response of insulin-producing cells to elevation of glucose levels.</jats:p>
<jats:p>RESEARCH DESIGN AND METHODS—We used insulinoma-1E cells to analyze the effects of miR-375 on PDK1 protein level and downstream signaling using Western blotting, glucose-induced insulin gene expression using quantitative RT-PCR, and DNA synthesis by measuring thymidine incorporation. Moreover, we analyzed the effect of glucose on miR-375 expression in both INS-1E cells and primary rat islets. Finally, miR-375 expression in isolated islets was analyzed in diabetic Goto-Kakizaki (GK) rats.</jats:p>
<jats:p>RESULTS—We found that miR-375 directly targets PDK1 and reduces its protein level, resulting in decreased glucose-stimulatory action on insulin gene expression and DNA synthesis. Furthermore, glucose leads to a decrease in miR-375 precursor level and a concomitant increase in PDK1 protein. Importantly, regulation of miR-375 expression by glucose occurs in primary rat islets as well. Finally, miR-375 expression was found to be decreased in fed diabetic GK rat islets.</jats:p>
<jats:p>CONCLUSIONS—Our findings provide evidence for a role of a pancreatic-specific microRNA, miR-375, in the regulation of PDK1, a key molecule in PI 3-kinase signaling in pancreatic β-cells. The effects of glucose on miR-375 are compatible with the idea that miR-375 is involved in glucose regulation of insulin gene expression and β-cell growth.</jats:p> |
| container_issue |
10 |
| container_start_page |
2708 |
| container_title |
Diabetes |
| container_volume |
57 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792348649359933445 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T18:14:32.317Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=miR-375+Targets+3%E2%80%B2-Phosphoinositide%E2%80%93Dependent+Protein+Kinase-1+and+Regulates+Glucose-Induced+Biological+Responses+in+Pancreatic+%CE%B2-Cells&rft.date=2008-10-01&genre=article&issn=1939-327X&volume=57&issue=10&spage=2708&epage=2717&pages=2708-2717&jtitle=Diabetes&atitle=miR-375+Targets+3%E2%80%B2-Phosphoinositide%E2%80%93Dependent+Protein+Kinase-1+and+Regulates+Glucose-Induced+Biological+Responses+in+Pancreatic+%CE%B2-Cells&aulast=van+Obberghen&aufirst=Emmanuel&rft_id=info%3Adoi%2F10.2337%2Fdb07-1614&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792348649359933445 |
| author | El Ouaamari, Abdelfattah, Baroukh, Nadine, Martens, Geert A., Lebrun, Patricia, Pipeleers, Daniel, van Obberghen, Emmanuel |
| author_facet | El Ouaamari, Abdelfattah, Baroukh, Nadine, Martens, Geert A., Lebrun, Patricia, Pipeleers, Daniel, van Obberghen, Emmanuel, El Ouaamari, Abdelfattah, Baroukh, Nadine, Martens, Geert A., Lebrun, Patricia, Pipeleers, Daniel, van Obberghen, Emmanuel |
| author_sort | el ouaamari, abdelfattah |
| container_issue | 10 |
| container_start_page | 2708 |
| container_title | Diabetes |
| container_volume | 57 |
| description | <jats:p>OBJECTIVE—MicroRNAs are short, noncoding RNAs that regulate gene expression. We hypothesized that the phosphatidylinositol 3-kinase (PI 3-kinase) cascade known to be important in β-cell physiology could be regulated by microRNAs. Here, we focused on the pancreas-specific miR-375 as a potential regulator of its predicted target 3′-phosphoinositide–dependent protein kinase-1 (PDK1), and we analyzed its implication in the response of insulin-producing cells to elevation of glucose levels.</jats:p> <jats:p>RESEARCH DESIGN AND METHODS—We used insulinoma-1E cells to analyze the effects of miR-375 on PDK1 protein level and downstream signaling using Western blotting, glucose-induced insulin gene expression using quantitative RT-PCR, and DNA synthesis by measuring thymidine incorporation. Moreover, we analyzed the effect of glucose on miR-375 expression in both INS-1E cells and primary rat islets. Finally, miR-375 expression in isolated islets was analyzed in diabetic Goto-Kakizaki (GK) rats.</jats:p> <jats:p>RESULTS—We found that miR-375 directly targets PDK1 and reduces its protein level, resulting in decreased glucose-stimulatory action on insulin gene expression and DNA synthesis. Furthermore, glucose leads to a decrease in miR-375 precursor level and a concomitant increase in PDK1 protein. Importantly, regulation of miR-375 expression by glucose occurs in primary rat islets as well. Finally, miR-375 expression was found to be decreased in fed diabetic GK rat islets.</jats:p> <jats:p>CONCLUSIONS—Our findings provide evidence for a role of a pancreatic-specific microRNA, miR-375, in the regulation of PDK1, a key molecule in PI 3-kinase signaling in pancreatic β-cells. The effects of glucose on miR-375 are compatible with the idea that miR-375 is involved in glucose regulation of insulin gene expression and β-cell growth.</jats:p> |
| doi_str_mv | 10.2337/db07-1614 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMjMzNy9kYjA3LTE2MTQ |
| imprint | American Diabetes Association, 2008 |
| imprint_str_mv | American Diabetes Association, 2008 |
| institution | DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1 |
| issn | 0012-1797, 1939-327X |
| issn_str_mv | 0012-1797, 1939-327X |
| language | English |
| last_indexed | 2024-03-01T18:14:32.317Z |
| match_str | elouaamari2008mir375targets3phosphoinositidedependentproteinkinase1andregulatesglucoseinducedbiologicalresponsesinpancreaticbcells |
| mega_collection | American Diabetes Association (CrossRef) |
| physical | 2708-2717 |
| publishDate | 2008 |
| publishDateSort | 2008 |
| publisher | American Diabetes Association |
| record_format | ai |
| recordtype | ai |
| series | Diabetes |
| source_id | 49 |
| spelling | El Ouaamari, Abdelfattah Baroukh, Nadine Martens, Geert A. Lebrun, Patricia Pipeleers, Daniel van Obberghen, Emmanuel 0012-1797 1939-327X American Diabetes Association Endocrinology, Diabetes and Metabolism Internal Medicine http://dx.doi.org/10.2337/db07-1614 <jats:p>OBJECTIVE—MicroRNAs are short, noncoding RNAs that regulate gene expression. We hypothesized that the phosphatidylinositol 3-kinase (PI 3-kinase) cascade known to be important in β-cell physiology could be regulated by microRNAs. Here, we focused on the pancreas-specific miR-375 as a potential regulator of its predicted target 3′-phosphoinositide–dependent protein kinase-1 (PDK1), and we analyzed its implication in the response of insulin-producing cells to elevation of glucose levels.</jats:p> <jats:p>RESEARCH DESIGN AND METHODS—We used insulinoma-1E cells to analyze the effects of miR-375 on PDK1 protein level and downstream signaling using Western blotting, glucose-induced insulin gene expression using quantitative RT-PCR, and DNA synthesis by measuring thymidine incorporation. Moreover, we analyzed the effect of glucose on miR-375 expression in both INS-1E cells and primary rat islets. Finally, miR-375 expression in isolated islets was analyzed in diabetic Goto-Kakizaki (GK) rats.</jats:p> <jats:p>RESULTS—We found that miR-375 directly targets PDK1 and reduces its protein level, resulting in decreased glucose-stimulatory action on insulin gene expression and DNA synthesis. Furthermore, glucose leads to a decrease in miR-375 precursor level and a concomitant increase in PDK1 protein. Importantly, regulation of miR-375 expression by glucose occurs in primary rat islets as well. Finally, miR-375 expression was found to be decreased in fed diabetic GK rat islets.</jats:p> <jats:p>CONCLUSIONS—Our findings provide evidence for a role of a pancreatic-specific microRNA, miR-375, in the regulation of PDK1, a key molecule in PI 3-kinase signaling in pancreatic β-cells. The effects of glucose on miR-375 are compatible with the idea that miR-375 is involved in glucose regulation of insulin gene expression and β-cell growth.</jats:p> miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells Diabetes |
| spellingShingle | El Ouaamari, Abdelfattah, Baroukh, Nadine, Martens, Geert A., Lebrun, Patricia, Pipeleers, Daniel, van Obberghen, Emmanuel, Diabetes, miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells, Endocrinology, Diabetes and Metabolism, Internal Medicine |
| title | miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_full | miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_fullStr | miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_full_unstemmed | miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_short | miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| title_sort | mir-375 targets 3′-phosphoinositide–dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic β-cells |
| title_unstemmed | miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells |
| topic | Endocrinology, Diabetes and Metabolism, Internal Medicine |
| url | http://dx.doi.org/10.2337/db07-1614 |