| Create Account | login

login

Publication

Skeletal muscle autophagy remains responsive to hyperinsulinemia and
hyperglycemia at higher plasma insulin concentrations in insulin-resistant mice.

Authors	Ehrlicher SE, Stierwalt HD, Newsom SA, Robinson MM
Submitted By	Submitted Externally on 8/20/2018
Status	Published
Journal	Physiological reports
Year	2018
Date Published	7/1/2018
Volume : Pages	6 : e13810
PubMed Reference	30047243
Abstract	Skeletal muscle autophagy is suppressed by insulin, but it is not clear if such suppression is altered with insulin resistance. We investigated if the inhibitory action of insulin on autophagy remains intact despite insulin resistance to glucose metabolism. C57BL/6J mice consumed either a low-fat (10% fat) diet as control or high-fat (60% fat) diet for 12 weeks to induce insulin resistance. Following a 5-hour fast, mice underwent either hyperinsulinemic-euglycemic, hyperinsulinemic-hyperglycemic, or saline infusion to test the effect of insulin on autophagy markers in the quadriceps muscle (n = 8-10 per diet and clamp condition). Mice were anesthetized by sodium pentobarbital for tissue collection after 2 h of infusion. Despite the high-fat group having lower insulin-stimulated glucose uptake, both low-fat and high-fat groups had similar autophagosome abundance during hyperinsulinemic conditions. The lipidation of microtubule-associated proteins 1A/1B light chain 3B (LC3II/LC3I) was decreased in hyperinsulinemia versus saline control (P < 0.01) in low-fat (-54%) and high-fat groups (-47%), demonstrating similar suppression of autophagy between diet groups. Mitochondrial-associated LC3II was greater in the high-fat compared to the low-fat group (P = 0.045) across clamp conditions, suggesting a greater localization of autophagosomes with mitochondria. L6 myotubes were treated with insulin and rapamycin to determine the role of mechanistic target of rapamycin complex-1 (mTORC1) in insulin-mediated suppression of autophagy. Inhibition of mTORC1 blunted the decline of LC3II/LC3I with insulin by 40%, suggesting mTORC1 partially mediates the insulin action to suppress autophagy. Collectively, autophagy remained responsive to the suppressive effects of insulin in otherwise insulin-resistant and obese mice.

Back to Top

Store Credentials?

MMPC-Live web resource – Terms of Use

Warranty disclaimer and copyright notice

THE MMPC-Live MAKES NO REPRESENTATION ABOUT THE SUITABILITY OR ACCURACY OF THE SOFTWARE OR DATA FOR ANY PURPOSE, AND MAKES NO WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR THAT THE USE OF THE SOFTWARE OR DATA WILL NOT INFRINGE ANY THIRD PARTY PATENTS, COPYRIGHTS, TRADEMARKS, OR OTHER RIGHTS. THE SOFTWARE AND DATA ARE PROVIDED "AS IS".

The Mouse Metabolic Phenotyping Centers (MMPC-Live) is an NIDDK funded consortium and adheres to the NIH Data Sharing Policy.

MMPC-Live clients make their data freely available whereby MMPC-Live users may freely build upon, enhance and reuse those data for any purpose without restriction. Scholarly citation norms must be followed for content reuse. Please acknowledge the MMPC-Live using the following text: 'The MMPC-Live data used in this manuscript was supported by the NIDDK National Mouse Metabolic Phenotyping Centers (MMPC-Live, RRID:SCR_008997, www.mmpc.org)'. To cite specific MMPC-Live centers, please use the appropriate RRID available from the MMPC-Live website (https://www.mmpc.org/shared/centers.aspx).

Please note that the acknowledgment text includes a Research Resource Identifier (RRID) for the MMPC-Live CU and Centers. Reproducibility is one of the corner stones of effective, open and transparent biomedical published research. However, too often, resources (e.g. model organisms, antibodies, and tools) are not reported with adequate detail to ensure others can replicate or expand upon the published results. The Research Resource Identification Initiative (#RII) seeks to change these limitations in reporting by the use of unique Research Resource Identifiers (RRIDs). This initiative is designed to encourage authors to provide identification of the types of resources used in their research by adding a globally unique accession number to the resources described in the their manuscripts. These identifiers, called RRIDs, will allow authors to cite the resources that they use in their manuscripts. RRIDs allow for easy tracking of all papers that have used the same resource making it easy to access how the same resources works in other scenarios.

It is expected that MMPC-Live users follow scholarly citation norms, giving credit to fellow scholars when accessing/using protocols and data, including data derived by MMPC-Live (such as summary data) and any plots, tables or screenshots depicting those data.

It is possible for invalid or incomplete results to be presented on the MMPC-Live web site due to software bugs, data problems, or artifacts of human error. Data sets are not necessarily static; we reserve the right to post corrections and updates as needed.

Prohibited use. Data contributors and data users may not use MMPC-Live in any unlawful manner, or in any manner that could impair MMPC-Live services, security or functionality. Automated usage (webcrawlers and similar) must observe each page's "meta robots" html tags and space requests by ≥ 2 seconds. We reserve the right to block any IP associated with what we consider to be excessive or abusive usage patterns, and/or to take any action we deem necessary.

MMPC-Live is a National Institutes of Health-sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice.

Menu

Home

Contact

About MMPC

Animal Husbandry

Tests Data

Search Data

Analysis

Clients

MMPC Centers

Newsletter

Interested in receiving MMPC News?

Mouse Phenotyping
@NationalMMPC

2017 National MMPC. All Rights Reserved.