title: The A54T polymorphism of fatty acid-binding protein 2 may entail a reduction in fat-stimulated secretion of GIP that potentiates the adverse impact of fatty diets on insulin sensitivity.
abstract: A common polymorphism of the 54th codon of fatty acid-binding protein 2 (FABP2), in which threonine substitutes for alanine (T54), has been linked to insulin resistance and/or increased postprandial triglycerides in various studies. I propose that, in subjects expressing T54, the secretion of gastric inhibitory polypeptide (GIP) evoked by fatty meals is subnormal, such that adipocytes are less efficient in converting chylomicrons to stored triglyceride. The increased postprandial free fatty acid flux which this may imply could be expected to exacerbate insulin resistance syndrome--thus accounting for the association of T54 with insulin resistance in epidemiological studies. If this thesis proves to be correct, it will help to clarify the importance of appropriate GIP secretion to maintenance of insulin sensitivity in the context of fatty diets.
mesh_terms: D000409:Alanine / Q000737:chemistry; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D004041:Dietary Fats; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008962:Models, Theoretical; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000737:chemistry; D025521:Tumor Suppressor Proteins
chemical_list: D002352:Carrier Proteins; D004041:Dietary Fats; C493404:FABP2 protein, human; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D014280:Triglycerides; D025521:Tumor Suppressor Proteins; D005749:Gastric Inhibitory Polypeptide; D000409:Alanine