Article abstract
Nature Medicine 13, 455 - 462 (2007)
Published online: 11 March 2007 | doi:10.1038/nm1550
Bone marrow–specific Cap gene deletion protects against high-fat diet–induced insulin resistance
Lisa A Lesniewski1, Sarah E Hosch1, Jaap G Neels1, Carl de Luca1, Mohammad Pashmforoush2, Carey N Lumeng3,4, Shian-Huey Chiang3, Miriam Scadeng5, Alan R Saltiel3 & Jerrold M Olefsky1
Abstract
Cbl-associated protein (Cap) is a member of a phosphatidylinositol 3-kinase–independent pathway for insulin-stimulated translocation of the glucose transporter GLUT4. Despite this positive role of Cap in glucose uptake, here we show that deletion of the gene encoding Cap (official gene name: Sorbs1) protects against high-fat diet (HFD)–induced insulin resistance in mice while also having an opposite, insulin-sensitizing effect, accompanied by reduced tissue markers of inflammation. Given the emerging role of chronic inflammation in insulin resistance and the macrophage in initiating this inflammatory process, we considered that Sorbs1 deletion from macrophages may have resulted in the observed protection from HFD-induced insulin resistance. Using bone marrow transplantation to generate functional Sorbs1-null macrophages, we show that the insulin-sensitive phenotype can be transferred to wild-type mice by transplantation of Sorbs1-null bone marrow. These studies show that macrophages are an important cell type in the induction of insulin resistance and that Cap has a modulatory role in this function.
- Department of Endocrinology and Metabolism, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
- Institute for Genetic Medicine, 2250 Alcazar Street, CSC 240, Los Angeles, California 90033, USA.
- Life Sciences Institute, Departments of Internal Medicine and Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
- Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109, USA.
- Department of Radiology, University of California at San Diego, San Diego, California 92098, USA.
Correspondence to: Jerrold M Olefsky1 e-mail: jolefsky@ucsd.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesisThe EMBO Journal Article (07 Mar 2007)
Bone marrow?specific Cap gene deletion protects against high-fat diet?induced insulin resistanceNature Medicine Article (01 Apr 2007)
Bone marrow?specific Cap gene deletion protects against high-fat diet?induced insulin resistanceNature Medicine Article
Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetesNature Article (21 Jul 2005)
See all 60 matches for Research
