دورية أكاديمية
The Akt substrate Girdin is a regulator of insulin signaling in myoblast cells.
| العنوان: | The Akt substrate Girdin is a regulator of insulin signaling in myoblast cells. |
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| المؤلفون: | Hartung A; Department of Internal Medicine IV, Otfried-Müller Str.10, 72076 Tübingen, Germany., Ordelheide AM; Department of Internal Medicine IV, Otfried-Müller Str.10, 72076 Tübingen, Germany., Staiger H; Department of Internal Medicine IV, Otfried-Müller Str.10, 72076 Tübingen, Germany., Melzer M; Department of Internal Medicine IV, Otfried-Müller Str.10, 72076 Tübingen, Germany., Häring HU; Department of Internal Medicine IV, Otfried-Müller Str.10, 72076 Tübingen, Germany., Lammers R; Department of Internal Medicine IV, Otfried-Müller Str.10, 72076 Tübingen, Germany. Electronic address: reiner.lammers@med.uni-tuebingen.de. |
| المصدر: | Biochimica et biophysica acta [Biochim Biophys Acta] 2013 Dec; Vol. 1833 (12), pp. 2803-2811. Date of Electronic Publication: 2013 Jul 23. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Pub. Co Country of Publication: Netherlands NLM ID: 0217513 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-3002 (Print) Linking ISSN: 00063002 NLM ISO Abbreviation: Biochim Biophys Acta Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Pub. Co. |
| مواضيع طبية MeSH: | Signal Transduction*/drug effects, Insulin/*metabolism , Microfilament Proteins/*metabolism , Myoblasts/*metabolism , Proto-Oncogene Proteins c-abl/*metabolism , Proto-Oncogene Proteins c-akt/*metabolism , Vesicular Transport Proteins/*metabolism, Adult ; Animals ; Cells, Cultured ; Down-Regulation/drug effects ; Endocytosis/drug effects ; Enzyme Activation/drug effects ; Female ; Gene Knockdown Techniques ; Glycogen/biosynthesis ; Humans ; Insulin/pharmacology ; Male ; Mice ; Myoblasts/drug effects ; Myoblasts/enzymology ; Phosphorylation/drug effects ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptor, Insulin/metabolism ; Substrate Specificity/drug effects |
| مستخلص: | Akt kinases are important mediators of the insulin signal, and some Akt substrates are directly involved in glucose homeostasis. Recently, Girdin has been described as an Akt substrate that is expressed ubiquitously in mammals. Cells overexpressing Girdin show an enhanced Akt activity. However, not much is known about Girdin's role in insulin signaling. We therefore analyzed the role of Girdin in primary human myotubes and found a correlation between Girdin expression and insulin sensitivity of the muscle biopsy donors, as measured by a hyperinsulinemic-euglycemic clamp. To understand this finding on a cellular level, we then investigated the function of Girdin in C2C12 mouse myoblasts. Girdin knock-down reduced Akt and insulin receptor substrate-1 phosphorylation. In contrast, stable overexpression of Girdin in C2C12 cells strikingly increased insulin sensitivity through a massive upregulation of the insulin receptor and enhanced tyrosine phosphorylation of insulin receptor substrate-1. Furthermore, Akt and c-Abl kinases were constitutively activated. To investigate medium-term insulin responses we measured glucose incorporation into glycogen. The Girdin overexpressing cells showed a high basal glycogen synthesis that peaked already at 1nM insulin. Taken together, we characterized Girdin as a new and major regulator of the insulin signal in myoblasts and skeletal muscle. (© 2013.) |
| فهرسة مساهمة: | Keywords: Abl; Akt; C2C12; Girdin; Insulin sensitivity |
| المشرفين على المادة: | 0 (CCDC88A protein, human) 0 (Insulin) 0 (Microfilament Proteins) 0 (RNA, Messenger) 0 (Vesicular Transport Proteins) 0 (girdin protein, mouse) 9005-79-2 (Glycogen) EC 2.7.10.1 (Receptor, Insulin) EC 2.7.10.2 (Proto-Oncogene Proteins c-abl) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
| تواريخ الأحداث: | Date Created: 20130727 Date Completed: 20140224 Latest Revision: 20170915 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.bbamcr.2013.07.012 |
| PMID: | 23886629 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0006-3002 |
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| DOI: | 10.1016/j.bbamcr.2013.07.012 |