title: Partial inactivation of Ankrd26 causes diabetes with enhanced insulin responsiveness of adipose tissue in mice.
abstract: OBJECTIVE
  ANKRD26 is a newly described gene located at 10p12 in humans, a locus that has been identified with some forms of hereditary obesity. Previous studies have shown that partial inactivation of Ankrd26 in mice causes hyperphagia, obesity and gigantism. Hypothesising that Ankrd26 mutant (MT) mice could develop diabetes, we sought to establish whether the observed phenotype could be (1) solely related to the development of obesity or (2) caused by a direct action of ankyrin repeat domain 26 (ANKRD26) in peripheral tissues.
  
  
  METHODS
  To test the hypothesis, we did a full metabolic characterisation of Ankrd26 MT mice that had free access to chow or were placed under two different energy-restricted dietary regimens.
  
  
  RESULTS
  Highly obese Ankrd26 MT mice developed an unusual form of diabetes in which white adipose tissue is insulin-sensitive, while other tissues are insulin-resistant. When obese MT mice were placed on a food-restricted diet, their weight and glucose homeostasis returned to normal. In addition, when young MT mice were placed on a pair-feeding diet with normal mice, they maintained normal body weight, but showed better glucose tolerance than normal mice, an increased responsiveness of white adipose tissue to insulin and enhanced phosphorylation of the insulin receptor.
  
  
  CONCLUSIONS
  These findings show that the ANKRD26 protein has at least two functions in mice. One is to control the response of white adipose tissue to insulin; the other is to control appetite, which when Ankrd26 is mutated, leads to hyperphagia and diabetes in an obesity-dependent manner.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4264, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Raciti
authors.forename: T K
authors.initials: TK
authors.lastname: Bera
authors.forename: O
authors.initials: O
authors.lastname: Gavrilova
authors.forename: I
authors.initials: I
authors.lastname: Pastan
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D001069:Appetite Regulation; D031204:Caloric Restriction; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D050505:Mutant Proteins / Q000502:physiology; D009765:Obesity / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D009928:Organ Specificity; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011897:Random Allocation; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: C526207:Ankrd26 protein, mouse; D004268:DNA-Binding Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D014157:Transcription Factors; D011972:Receptor, Insulin