title: Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function.
abstract: To determine the roles of insulin and insulin-like growth factor 1 (IGF-1) action in adipose tissue, we created mice lacking the insulin receptor (IR), IGF-1 receptor (IGF1R), or both using Cre-recombinase driven by the adiponectin promoter. Mice lacking IGF1R only (F-IGFRKO) had a ∼25% reduction in white adipose tissue (WAT) and brown adipose tissue (BAT), whereas mice lacking both IR and IGF1R (F-IR/IGFRKO) showed an almost complete absence of WAT and BAT. Interestingly, mice lacking only the IR (F-IRKO) had a 95% reduction in WAT, but a paradoxical 50% increase in BAT with accumulation of large unilocular lipid droplets. Both F-IRKO and F-IR/IGFRKO mice were unable to maintain body temperature in the cold and developed severe diabetes, ectopic lipid accumulation in liver and muscle, and pancreatic islet hyperplasia. Leptin treatment normalized blood glucose levels in both groups. Glucose levels also improved spontaneously by 1 year of age, despite sustained lipodystrophy and insulin resistance. Thus, loss of IR is sufficient to disrupt white fat formation, but not brown fat formation and/or maintenance, although it is required for normal BAT function and temperature homeostasis. IGF1R has only a modest contribution to both WAT and BAT formation and function.
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Boucher
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA.
authors.forename: Samir
authors.initials: S
authors.lastname: Softic
authors.affiliation: Islet Cell and Regenerative Medicine, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: Abdelfattah
authors.initials: A
authors.lastname: El Ouaamari
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Krumpoch
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: Andre
authors.initials: A
authors.lastname: Kleinridders
authors.affiliation: Islet Cell and Regenerative Medicine, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: O'Neill
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA c.ronald.kahn@joslin.harvard.edu.
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D006943:Hyperglycemia / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology; D008060:Lipodystrophy / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010101:Oxygen Consumption / Q000502:physiology; D015531:Radioimmunoprecipitation Assay; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D007328:Insulin; D020738:Leptin; D013385:Succinate Dehydrogenase; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin