title: A CD36 nonsense mutation associated with insulin resistance and familial type 2 diabetes.
abstract: Mutations in CD36 / fatty acid translocase (FAT) gene are responsible for insulin resistance in the rat but contribution to human Type 2 diabetes is unknown. A nominal evidence for linkage of familial T2D at the CD36 locus led us to identify a rare nonsense mutation c.1079T>G (p.L360X) in one Caucasian pedigree presenting with autosomal dominant diabetes. Adiponectin levels, as marker of insulin sensitivity, were found to be significantly lower in the p.L360X variant carriers compared to homozygous for wild type CD36. Furthermore, expression studies of the truncated protein showed a defective binding of acetylated-LDL. Thus, our findings suggest a possible role for CD36 in the pathogenesis of T2D associated with reduced insulin sensitivity.
authors.affiliation: CNRS 8090-Institute of Biology, Pasteur Institute, Lille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Leprêtre
authors.forename: Francis
authors.initials: F
authors.lastname: Vasseur
authors.forename: Martine
authors.initials: M
authors.lastname: Vaxillaire
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Saira
authors.initials: S
authors.lastname: Ali
authors.forename: Kenneth
authors.initials: K
authors.lastname: Linton
authors.forename: Timothy
authors.initials: T
authors.lastname: Aitman
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: D052242:Adiponectin; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002457:Cell Extracts / Q000737:chemistry; D002460:Cell Line; D018389:Codon, Nonsense / Q000235:genetics* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011506:Proteins / Q000378:metabolism
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D018955:CD36 Antigens; D002457:Cell Extracts; D018389:Codon, Nonsense; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins