Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Diabetes. 2009 Jan;58(1):116-24. doi: 10.2337/db07-1839. Epub 2008 Oct 24.

Skeletal muscle-specific deletion of lipoprotein lipase enhances insulin signaling in skeletal muscle but causes insulin resistance in liver and other tissues.

Author information

  • 1Division of Endocrinology, Metabolism and Diabetes, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA.

Erratum in

  • Diabetes. 2010 Mar;59(3):756.

Abstract

OBJECTIVE:

Skeletal muscle-specific LPL knockout mouse (SMLPL(-/-)) were created to study the systemic impact of reduced lipoprotein lipid delivery in skeletal muscle on insulin sensitivity, body weight, and composition.

RESEARCH DESIGN AND METHODS:

Tissue-specific insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp and 2-deoxyglucose uptake. Gene expression and insulin-signaling molecules were compared in skeletal muscle and liver of SMLPL(-/-) and control mice.

RESULTS:

Nine-week-old SMLPL(-/-) mice showed no differences in body weight, fat mass, or whole-body insulin sensitivity, but older SMLPL(-/-) mice had greater weight gain and whole-body insulin resistance. High-fat diet feeding accelerated the development of obesity. In young SMLPL(-/-) mice, insulin-stimulated glucose uptake was increased 58% in the skeletal muscle, but was reduced in white adipose tissue (WAT) and heart. Insulin action was also diminished in liver: 40% suppression of hepatic glucose production in SMLPL(-/-) vs. 90% in control mice. Skeletal muscle triglyceride was 38% lower, and insulin-stimulated phosphorylated Akt (Ser473) was twofold greater in SMLPL(-/-) mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase activity. Hepatic triglyceride and liver X receptor, carbohydrate response element-binding protein, and PEPCK mRNAs were unaffected in SMLPL(-/-) mice, but peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and interleukin-1beta mRNAs were higher, and stearoyl-coenzyme A desaturase-1 and PPARgamma mRNAs were reduced.

CONCLUSIONS:

LPL deletion in skeletal muscle reduces lipid storage and increases insulin signaling in skeletal muscle without changes in body composition. Moreover, lack of LPL in skeletal muscle results in insulin resistance in other key metabolic tissues and ultimately leads to obesity and systemic insulin resistance.

Comment in

PMID:
18952837
[PubMed - indexed for MEDLINE]
PMCID:
PMC2606858
Free PMC Article

Images from this publication.See all images (6)Free text

FIG. 1.
FIG. 2.
FIG. 3.
FIG. 4.
FIG. 5.
FIG. 6.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk