title: Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue.
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.
authors.affiliation: Department of Pediatrics, Division of Neonatology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Kurlawalla-Martinez
authors.forename: Bangyan
authors.initials: B
authors.lastname: Stiles
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Sherin U
authors.initials: SU
authors.lastname: Devaskar
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Kahn
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D006729:Hormones, Ectopic / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000378:metabolism; D032342:Muscle Cells / Q000378:metabolism; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism; D051059:PTEN Phosphohydrolase; D010179:Pancreas / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D052243:Resistin; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D006729:Hormones, Ectopic; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D052243:Resistin; D025521:Tumor Suppressor Proteins; C499623:Retn protein, mouse; C495693:Slc2a4 protein, mouse
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