PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation
Insulin resistance is a syndrome that affects multiple insulin target tissues, each having different biological functions regulated by insulin. A remaining question is to mechanistically explain how an insulin target cell/tissue can be insulin resistant in one biological function and insulin sensiti...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715009559 |
| _version_ | 1811337644615925760 |
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| author | Barbara Leibiger Tilo Moede Meike Paschen Na-Oh Yunn Jong Hoon Lim Sung Ho Ryu Teresa Pereira Per-Olof Berggren Ingo B. Leibiger |
| author_facet | Barbara Leibiger Tilo Moede Meike Paschen Na-Oh Yunn Jong Hoon Lim Sung Ho Ryu Teresa Pereira Per-Olof Berggren Ingo B. Leibiger |
| author_sort | Barbara Leibiger |
| collection | DOAJ |
| description | Insulin resistance is a syndrome that affects multiple insulin target tissues, each having different biological functions regulated by insulin. A remaining question is to mechanistically explain how an insulin target cell/tissue can be insulin resistant in one biological function and insulin sensitive in another at the same time. Here, we provide evidence that in pancreatic β cells, knockdown of PI3K-C2α expression results in rerouting of the insulin signal from insulin receptor (IR)-B/PI3K-C2α/PKB-mediated metabolic signaling to IR-B/Shc/ERK-mediated mitogenic signaling, which allows the β cell to switch from a highly glucose-responsive, differentiated state to a proliferative state. Our data suggest the existence of IR-cascade-selective insulin resistance, which allows rerouting of the insulin signal within the same target cell. Hence, factors involved in the rerouting of the insulin signal represent tentative therapeutic targets in the treatment of insulin resistance. |
| first_indexed | 2024-04-13T17:57:51Z |
| format | Article |
| id | doaj.art-579433b1afa946ba860b86f60e89c2ef |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T17:57:51Z |
| publishDate | 2015-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-579433b1afa946ba860b86f60e89c2ef2022-12-22T02:36:22ZengElsevierCell Reports2211-12472015-10-01131152210.1016/j.celrep.2015.08.058PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell ProliferationBarbara Leibiger0Tilo Moede1Meike Paschen2Na-Oh Yunn3Jong Hoon Lim4Sung Ho Ryu5Teresa Pereira6Per-Olof Berggren7Ingo B. Leibiger8The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76 Stockholm, SwedenThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76 Stockholm, SwedenThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76 Stockholm, SwedenSchool of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Republic of KoreaAptamer Initiative Program, Pohang University of Science and Technology, Pohang 790-784, Republic of KoreaSchool of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Republic of KoreaThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76 Stockholm, SwedenThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76 Stockholm, SwedenThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76 Stockholm, SwedenInsulin resistance is a syndrome that affects multiple insulin target tissues, each having different biological functions regulated by insulin. A remaining question is to mechanistically explain how an insulin target cell/tissue can be insulin resistant in one biological function and insulin sensitive in another at the same time. Here, we provide evidence that in pancreatic β cells, knockdown of PI3K-C2α expression results in rerouting of the insulin signal from insulin receptor (IR)-B/PI3K-C2α/PKB-mediated metabolic signaling to IR-B/Shc/ERK-mediated mitogenic signaling, which allows the β cell to switch from a highly glucose-responsive, differentiated state to a proliferative state. Our data suggest the existence of IR-cascade-selective insulin resistance, which allows rerouting of the insulin signal within the same target cell. Hence, factors involved in the rerouting of the insulin signal represent tentative therapeutic targets in the treatment of insulin resistance.http://www.sciencedirect.com/science/article/pii/S2211124715009559 |
| spellingShingle | Barbara Leibiger Tilo Moede Meike Paschen Na-Oh Yunn Jong Hoon Lim Sung Ho Ryu Teresa Pereira Per-Olof Berggren Ingo B. Leibiger PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation Cell Reports |
| title | PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation |
| title_full | PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation |
| title_fullStr | PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation |
| title_full_unstemmed | PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation |
| title_short | PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation |
| title_sort | pi3k c2α knockdown results in rerouting of insulin signaling and pancreatic beta cell proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715009559 |
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