Source:http://linkedlifedata.com/resource/pubmed/id/20685876
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2010-9-22
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pubmed:abstractText |
Glucagon-like peptide-1 augments nutrient-stimulated insulin secretion. Chow-fed mice lacking the glucagon-like peptide-1 receptor (Glp1r) exhibit enhanced insulin-stimulated muscle glucose uptake but impaired suppression of endogenous glucose appearance (endoRa). This proposes a novel role for the Glp1r to regulate the balance of glucose disposal in muscle and liver by modulating insulin action. Whether this is maintained in an insulin-resistant state is unknown. The present studies tested the hypothesis that disruption of Glp1r expression overcomes high-fat (HF) diet-induced muscle insulin resistance and exacerbates HF diet-induced hepatic insulin resistance. Mice with a functional disruption of the Glp1r (Glp1r-/-) were compared with wild-type littermates (Glp1r+/+) after 12 wk on a regular chow diet or a HF diet. Arterial and venous catheters were implanted for sampling and infusions. Hyperinsulinemic-euglycemic clamps were performed on weight-matched male mice. [3-(3)H]glucose was used to determine glucose turnover, and 2[14C]deoxyglucose was used to measure the glucose metabolic index, an indicator of glucose uptake. Glp1r-/- mice exhibited increased glucose disappearance and muscle glucose metabolic index on either diet. This was associated with enhanced activation of muscle Akt and AMP-activated protein kinase and reduced muscle triglycerides in HF-fed Glp1r-/- mice. Chow-fed Glp1r-/- mice exhibited impaired suppression of endoRa and hepatic insulin signaling. In contrast, HF-fed Glp1r-/- mice exhibited improved suppression of endoRa and hepatic Akt activation. This was associated with decreased hepatic triglycerides and impaired activation of sterol regulatory element-binding protein-1. These results show that mice lacking the Glp1r are protected from HF diet-induced muscle and hepatic insulin resistance independent of effects on total fat mass.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/glucagon-like peptide receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1945-7170
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
151
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4678-87
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:20685876-Adiposity,
pubmed-meshheading:20685876-Animals,
pubmed-meshheading:20685876-Diet, Atherogenic,
pubmed-meshheading:20685876-Dietary Fats,
pubmed-meshheading:20685876-Female,
pubmed-meshheading:20685876-Glucose,
pubmed-meshheading:20685876-Insulin,
pubmed-meshheading:20685876-Insulin Resistance,
pubmed-meshheading:20685876-Liver,
pubmed-meshheading:20685876-Male,
pubmed-meshheading:20685876-Mice,
pubmed-meshheading:20685876-Mice, Inbred C57BL,
pubmed-meshheading:20685876-Mice, Knockout,
pubmed-meshheading:20685876-Muscle, Skeletal,
pubmed-meshheading:20685876-Receptors, Glucagon,
pubmed-meshheading:20685876-Sex Characteristics
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pubmed:year |
2010
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pubmed:articleTitle |
Glucagon-like peptide-1 receptor knockout mice are protected from high-fat diet-induced insulin resistance.
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pubmed:affiliation |
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. jayala@sanfordburnham.org
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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