Abstract
In adipose tissue, insulin controls glucose and lipid metabolism through the intracellular mediators phosphatidylinositol 3-kinase and serine-threonine kinase AKT. Phosphatase and a tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, is hypothesized to inhibit the metabolic effects of insulin. Here we report the generation of mice lacking PTEN in adipose tissue. Loss of Pten results in improved systemic glucose tolerance and insulin sensitivity, associated with decreased fasting insulin levels, increased recruitment of the glucose transporter isoform 4 to the cell surface in adipose tissue, and decreased serum resistin levels. Mutant animals also exhibit increased insulin signaling and AMP kinase activity in the liver. Pten mutant mice are resistant to developing streptozotocin-induced diabetes. Adipose-specific Pten deletion, however, does not alter adiposity or plasma fatty acids. Our results demonstrate that in vivo PTEN is a potent negative regulator of insulin signaling and insulin sensitivity in adipose tissue. Furthermore, PTEN may be a promising target for nutritional and/or pharmacological interventions aimed at reversing insulin resistance.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adipocytes / metabolism
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Adipose Tissue / enzymology
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Adipose Tissue / metabolism*
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Animals
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Cell Membrane / chemistry
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Diabetes Mellitus, Experimental / enzymology*
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Diabetes Mellitus, Experimental / genetics
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Diabetes Mellitus, Experimental / metabolism
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Fatty Acids / blood
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Glucose Tolerance Test
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Glucose Transporter Type 4
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Hormones, Ectopic / blood
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Hormones, Ectopic / metabolism*
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Insulin / physiology*
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Insulin Resistance / genetics
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Insulin Resistance / physiology*
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Liver / metabolism
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Mice
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Mice, Knockout
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Monosaccharide Transport Proteins / analysis
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Monosaccharide Transport Proteins / metabolism
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Muscle Cells / metabolism
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Muscle Proteins / analysis
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Muscle Proteins / metabolism
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PTEN Phosphohydrolase
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Pancreas / cytology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / physiology*
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Protein Isoforms / metabolism
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Resistin
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Signal Transduction
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / physiology*
Substances
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Fatty Acids
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Glucose Transporter Type 4
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Hormones, Ectopic
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Insulin
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Monosaccharide Transport Proteins
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Muscle Proteins
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Protein Isoforms
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Proto-Oncogene Proteins
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Resistin
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Retn protein, mouse
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Slc2a4 protein, mouse
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Tumor Suppressor Proteins
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase