Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake
Insulin, downstream of Akt activation, promotes glucose uptake into fat and muscle cells to lower postprandial blood glucose, an enforced change in cellular metabolism to maintain glucose homeostasis. This effect is mediated by the Glut4 glucose transporter. Growth factors also enhance glucose uptak...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/26896 |
| _version_ | 1811235922834882560 |
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| author | Muheeb Beg Nazish Abdullah Fathima Shazna Thowfeik Nasser K Altorki Timothy E McGraw |
| author_facet | Muheeb Beg Nazish Abdullah Fathima Shazna Thowfeik Nasser K Altorki Timothy E McGraw |
| author_sort | Muheeb Beg |
| collection | DOAJ |
| description | Insulin, downstream of Akt activation, promotes glucose uptake into fat and muscle cells to lower postprandial blood glucose, an enforced change in cellular metabolism to maintain glucose homeostasis. This effect is mediated by the Glut4 glucose transporter. Growth factors also enhance glucose uptake to fuel an anabolic metabolism required for tissue growth and repair. This activity is predominantly mediated by the Glut1. Akt is activated by phosphorylation of its kinase and hydrophobic motif (HM) domains. We show that insulin-stimulated Glut4-mediated glucose uptake requires PDPK1 phosphorylation of the kinase domain but not mTORC2 phosphorylation of the HM domain. Nonetheless, an intact HM domain is required for Glut4-mediated glucose uptake. Whereas, Glut1-mediated glucose uptake also requires mTORC2 phosphorylation of the HM domain, demonstrating both phosphorylation-dependent and independent roles of the HM domain in regulating glucose uptake. Thus, mTORC2 links Akt to the distinct physiologic programs related to Glut4 and Glut1-mediated glucose uptake. |
| first_indexed | 2024-04-12T12:00:22Z |
| format | Article |
| id | doaj.art-682f7ad30cc64599b1291312d20a9dd6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:00:22Z |
| publishDate | 2017-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-682f7ad30cc64599b1291312d20a9dd62022-12-22T03:33:52ZengeLife Sciences Publications LtdeLife2050-084X2017-06-01610.7554/eLife.26896Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptakeMuheeb Beg0Nazish Abdullah1Fathima Shazna Thowfeik2Nasser K Altorki3Timothy E McGraw4https://orcid.org/0000-0001-9748-263XDepartment of Biochemistry, Weill Cornell Medicine, New York, United StatesDepartment of Biochemistry, Weill Cornell Medicine, New York, United StatesDepartment of Cardiothoracic Surgery, Weill Cornell Medicine, New York, United States; Lung Cancer Program, Meyer Cancer Center, Weill Cornell Medicine, New York, United StatesDepartment of Cardiothoracic Surgery, Weill Cornell Medicine, New York, United States; Lung Cancer Program, Meyer Cancer Center, Weill Cornell Medicine, New York, United StatesDepartment of Biochemistry, Weill Cornell Medicine, New York, United States; Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, United States; Lung Cancer Program, Meyer Cancer Center, Weill Cornell Medicine, New York, United StatesInsulin, downstream of Akt activation, promotes glucose uptake into fat and muscle cells to lower postprandial blood glucose, an enforced change in cellular metabolism to maintain glucose homeostasis. This effect is mediated by the Glut4 glucose transporter. Growth factors also enhance glucose uptake to fuel an anabolic metabolism required for tissue growth and repair. This activity is predominantly mediated by the Glut1. Akt is activated by phosphorylation of its kinase and hydrophobic motif (HM) domains. We show that insulin-stimulated Glut4-mediated glucose uptake requires PDPK1 phosphorylation of the kinase domain but not mTORC2 phosphorylation of the HM domain. Nonetheless, an intact HM domain is required for Glut4-mediated glucose uptake. Whereas, Glut1-mediated glucose uptake also requires mTORC2 phosphorylation of the HM domain, demonstrating both phosphorylation-dependent and independent roles of the HM domain in regulating glucose uptake. Thus, mTORC2 links Akt to the distinct physiologic programs related to Glut4 and Glut1-mediated glucose uptake.https://elifesciences.org/articles/26896AktmTORC2Glut4Glut1insulin action |
| spellingShingle | Muheeb Beg Nazish Abdullah Fathima Shazna Thowfeik Nasser K Altorki Timothy E McGraw Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake eLife Akt mTORC2 Glut4 Glut1 insulin action |
| title | Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake |
| title_full | Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake |
| title_fullStr | Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake |
| title_full_unstemmed | Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake |
| title_short | Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake |
| title_sort | distinct akt phosphorylation states are required for insulin regulated glut4 and glut1 mediated glucose uptake |
| topic | Akt mTORC2 Glut4 Glut1 insulin action |
| url | https://elifesciences.org/articles/26896 |
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