Artikel ; Online: Acute knockdown of the insulin receptor or its substrates Irs1 and 2 in 3T3-L1 adipocytes suppresses adiponectin production.
2016 Band 6, Seite(n) 21105
Abstract: Loss of function of the insulin receptor (INSR) in humans produces severe insulin resistance. Unlike "common" insulin resistance, this is associated with elevated plasma levels of the insulin-sensitising, adipose-derived protein adiponectin. The ... ...
| Abstract | Loss of function of the insulin receptor (INSR) in humans produces severe insulin resistance. Unlike "common" insulin resistance, this is associated with elevated plasma levels of the insulin-sensitising, adipose-derived protein adiponectin. The underlying mechanism for this paradox is unclear, and it is at odds with the acute stimulation of adiponectin secretion reported on insulin treatment of cultured adipocytes. Given recent evidence for ligand-independent actions of the INSR, we used a lentiviral system to knock down Insr or its substrates Irs1 and Irs2 conditionally in 3T3-L1 murine preadipocytes/adipocytes to assess whether acute loss of their expression has different consequences to withdrawal of insulin. Efficient knockdown of either Insr or Irs1/2 was achieved by conditional shRNA expression, severely attenuating insulin-stimulated AKT phosphorylation and glucose uptake. Dual knockdown of Irs1 and Irs2 but not Insr in preadipocytes impaired differentiation to adipocytes. Acute knockdown of Insr or both Irs1 and Irs2 in adipocytes increased Adipoq mRNA expression but reduced adiponectin secretion, assessed by immunoassay. Knockdown sustained for 14 days also reduced immunoassay-detected adiponectin secretion, and moreover induced delipidation of the cells. These findings argue against a distinct effect of Insr deficiency to promote adiponectin secretion as the explanation for paradoxical insulin receptoropathy-related hyperadiponectinaemia. |
|---|---|
| Mesh-Begriff(e) | 3T3-L1 Cells ; Adipocytes/metabolism ; Adiponectin/biosynthesis ; Adiponectin/genetics ; Animals ; Gene Expression Regulation ; Gene Knockdown Techniques ; Insulin Receptor Substrate Proteins/genetics ; Insulin Receptor Substrate Proteins/metabolism ; Mice ; Receptor, Insulin/genetics ; Receptor, Insulin/metabolism |
| Chemische Substanzen | Adiponectin ; Adipoq protein, mouse ; Insulin Receptor Substrate Proteins ; Irs1 protein, mouse ; Irs2 protein, mouse ; Receptor, Insulin (EC 2.7.10.1) |
| Sprache | Englisch |
| Erscheinungsdatum | 2016-02-18 |
| Erscheinungsland | England |
| Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/srep21105 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Volltext online
Zusatzmaterialien
Kategorien
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.