title: [Genetic defects in insulin signalling proteins. Implications for the pathogenesis of type 2 diabetes].
abstract: The pathogenesis of type 2 diabetes mellitus is complex and involves abnormalities in both the action and secretion of insulin. These abnormalities are caused by a complicated interplay between genes and environment. A determination of the genetic defects that predispose to either insulin resistance or decreased insulin secretion is important, as an improved understanding of the underlying molecular mechanisms may be essential for the development of the most effective treatment. This paper focuses on genetic variants identified in genes encoding proteins in the early insulin signalling cascade. Variations frequently occur in these genes, but their effect varies in different populations. This may suggest that the genetic background is a considerable factor and that the synergistic effect of several variants plays a major role. Future, genetic-epidemiological studies of large populations are therefore important in order to obtain sufficient statistical power. The paper also discusses recent results that suggests, that insulin itself has an effect on insulin secretion by the beta-cell and that insulin signalling in the CNS plays an important role in the regulation of energy disposal, fuel metabolism, and reproduction.
authors.affiliation: Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. katrine.almind@joslin.harvard.edu
authors.forename: Katrine
authors.initials: K
authors.lastname: Almind
mesh_terms: D000595:Amino Acid Sequence; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D008954:Models, Biological; D011972:Receptor, Insulin / Q000235:genetics; D015398:Signal Transduction
chemical_list: D007328:Insulin; D011972:Receptor, Insulin