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Naturally occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissues without change in AS160 activation.
Abstract: Although the importance of adipose tissue (AT) glucose transport in regulating whole-body insulin sensitivity is becoming increasingly evident and insulin resistance (IR) has been widely recognized, the underlying mechanisms of IR are still not well understood. The purpose of the present study was to determine the early pathological changes in glucose transport by characterizing the alterations in glucose transporters (GLUT) in multiple visceral and subcutaneous adipose depots in a large animal model of naturally occurring compensated IR. AT biopsies were collected from horses, which were classified as insulin-sensitive (IS) or compensated IR based on the results of an insulin-modified frequently sampled intravenous glucose tolerance test. Protein expression of GLUT4 (major isoform) and GLUT12 (one of the most recently discovered isoforms) were measured by Western blotting in multiple AT depots, as well as AS160 (a potential key player in GLUT trafficking pathway). Using a biotinylated bis-mannose photolabeled technique, active cell surface GLUT content was quantified. Omental AT had the highest total GLUT content compared to other sites during the IS state. IR was associated with a significantly reduced total GLUT4 content in omental AT, without a change in content in other visceral or subcutaneous adipose sites. In addition, active cell surface GLUT-4, but not -12, was significantly lower in AT of IR compared to IS horses, without change in AS160 phosphorylation between groups. Our data suggest that GLUT4, but not GLUT12, is a pathogenic factor in AT during naturally occurring compensated IR, despite normal AS160 activation.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication Date: 2011-02-23 PubMed ID: 21352908PubMed Central: PMC3143249DOI: 10.1016/j.bbadis.2011.02.007Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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This research explores how a naturally occurring insulin resistance impacts glucose transporters in fat tissues, with results indicating that the GLUT4 transporter could be implicated in disease onset but not GLUT12, under certain circumstances of insulin resistance.
Context and Purpose
- The study is aimed at understanding the role of adipose tissue (AT) – fat tissue – in regulating insulin sensitivity, an important aspect of diabetes research. Despite recognition of insulin resistance as a key aspect of metabolic disorders, the underlying mechanisms are still not fully understood.
- The researchers want to particularly understand the early pathological changes occurring in glucose transport. They aim to do this by studying changes to glucose transporters – proteins that help move glucose into cells – in various visceral (deep abdominal fat tissue) and subcutaneous (just beneath the skin) fat depots, in a large animal model of naturally occurring insulin resistance.
Methodology
- The researchers collected AT biopsies from horses. Based on insulin-modified frequently sampled intravenous glucose tolerance tests, the horses were classified as either insulin-sensitive (IS) or having compensated insulin resistance (IR).
- The researchers checked protein expression levels of two glucose transporters, GLUT4 and GLUT12, using a technique called Western blotting. GLUT4 is a major isoform, while GLUT12 is one of the most recently discovered ones. They also checked AS160 protein, which could potentially play a role in the Glut trafficking pathway.
- A technique called the biotinylated bis-mannose photolabeled technique was used to quantify active cell surface GLUT content.
Findings
- The omental AT (fat inside the abdominal cavity) had the highest total GLUT content during the insulin-sensitive state.
- Compensated IR was associated with a significant reduction in total GLUT4 content in the omental AT, but there was no change in content in other visceral or subcutaneous fat sites.
- Active cell surface GLUT4, but not GLUT12, was significantly lower in AT of IR compared to IS horses. However, the AS160 phosphorylation (an important process for protein function) didn’t show a difference between groups.
Implications
- The results suggest that a reduction in GLUT4, but not GLUT12, might be an underlying factor in the pathogenesis of compensated insulin resistance within adipose tissue.
- The observation that these changes occur despite normal AS160 activation imply that the GLUT4-mediated insulin resistance might happen via different mechanisms not necessarily linked to AS160 function.
Cite This Article
APA
Waller AP, Kohler K, Burns TA, Mudge MC, Belknap JK, Lacombe VA.
(2011).
Naturally occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissues without change in AS160 activation.
Biochim Biophys Acta, 1812(9), 1098-1103.
https://doi.org/10.1016/j.bbadis.2011.02.007 Publication
Researcher Affiliations
- College of Pharmacy, 500 W. 12th Avenue, The Ohio State University, Columbus, OH 43215, USA.
MeSH Terms
- Animals
- GTPase-Activating Proteins / physiology
- Glucose Tolerance Test / veterinary
- Glucose Transport Proteins, Facilitative / metabolism
- Glucose Transporter Type 4 / metabolism
- Horses
- Insulin Resistance / physiology
- Intra-Abdominal Fat / metabolism
- Intra-Abdominal Fat / pathology
- Subcutaneous Fat / metabolism
- Subcutaneous Fat / pathology
Grant Funding
- K01 RR023083 / NCRR NIH HHS
- K01 RR023083-03 / NCRR NIH HHS
- K01RR023083-01 / NCRR NIH HHS
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