title: Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance.
abstract: Although insulin regulates metabolism in both brown and white adipocytes, the role of these tissues in energy storage and utilization is quite different. Recombination technology using the Cre-loxP approach allows inactivation of the insulin receptor in a tissue-specific manner. Mice lacking insulin receptors in brown adipocytes show an age-dependent loss of interscapular brown fat but increased expression of uncoupling protein-1 and -2. In parallel, these mice develop an insulin-secretion defect resulting in a progressive glucose intolerance, without insulin resistance. This model provides direct evidence for not only a role for the insulin receptors in brown fat adipogenesis, the data also suggest a novel role of brown adipose tissue in the regulation of insulin secretion and glucose homeostasis.
authors.affiliation: Jackson Laboratory, Bar Harbor, Minnesota, USA.
authors.forename: C
authors.initials: C
authors.lastname: Guerra
authors.forename: P
authors.initials: P
authors.lastname: Navarro
authors.forename: A M
authors.initials: AM
authors.lastname: Valverde
authors.forename: M
authors.initials: M
authors.lastname: Arribas
authors.forename: J
authors.initials: J
authors.lastname: Brüning
authors.forename: L P
authors.initials: LP
authors.lastname: Kozak
authors.forename: C R
authors.initials: CR
authors.lastname: Kahn
authors.forename: M
authors.initials: M
authors.lastname: Benito
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution
chemical_list: D007328:Insulin; D012313:RNA; D011972:Receptor, Insulin