Summary of Study ST002204
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001407. The data can be accessed directly via it's Project DOI: 10.21228/M8V995 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST002204 |
Study Title | Endothelial Sirtuin1 Suppresses Whole-body Insulin Sensitivity by Modulating the Secretome |
Study Type | End point |
Study Summary | Sirtuin1 (Sirt1) in skeletal muscle (SK) and fat protects against metabolic damage by stimulating insulin sensitivity. Here we report that mice with selective deletion of endothelial Sirt1 (E-Sirt1-KO) paradoxically exhibit heightened whole-body insulin sensitivity. Akt phosphorylation, glucose uptake, and glycolysis are boosted in SK and brown adipose tissue (BAT) of E-Sirt1-KO mice. E-Sirt1-KO mice have higher energy expenditure and are partially protected from high-fat diet-induced insulin resistance. Enhanced insulin sensitivity and peripheral tissue Akt phosphorylation in E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation after surgical parabiosis. Silencing of Sirt1 in endothelial cells upregulates transcription of the F-actin-binding protein thymosin beta-4 (Tβ4), whose secretion activates Akt in skeletal myotubes. Sirt1 downregulation stimulates endothelial Tβ4 transcription through inhibition of autophagy and upregulation of nuclear factor-kappa B signaling. Thus, unlike Sirt1 in skeletal muscle and fat, endothelial Sirt1 curtails whole-body insulin sensitivity by inhibiting expression of secreted Tβ4 |
Institute | University of Iowa |
Department | Internal medicine |
Laboratory | irani |
Last Name | Irani |
First Name | Kaikobad |
Address | RM 2256 CBRB, Newton Rd, Iowa City, IA 52242 |
kaikobad-irani@uiowa.edu | |
Phone | 3193358821 |
Submit Date | 2021-12-02 |
Raw Data Available | Yes |
Raw Data File Type(s) | cdf |
Analysis Type Detail | GC-MS |
Release Date | 2022-07-22 |
Release Version | 1 |
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Project:
Project ID: | PR001407 |
Project DOI: | doi: 10.21228/M8V995 |
Project Title: | Endothelial Sirtuin1 Suppresses Whole-body Insulin Sensitivity by Modulating the Secretome |
Project Type: | Profiling metabolites in skeletal muscle |
Project Summary: | Profiling metabolites in skeletal muscle from wild type vs. endothelium-specific Sirt1 knockout (E-Sirt1-KO) mice. |
Institute: | University of Iowa |
Department: | Internal medicine |
Laboratory: | Irani lab |
Last Name: | Irani |
First Name: | Kaikobad |
Address: | RM 2256 CBRB, Newton Rd, Iowa City, IA 52242 |
Email: | kaikobad-irani@uiowa.edu |
Phone: | 319-335-8821 |
Funding Source: | AHA Award #20CDA35320042 |