title: Metabolic insights from extreme human insulin resistance phenotypes.
abstract: As well as improving diagnostic and clinical outcomes for affected patients, understanding the genetic basis of rare human metabolic disorders has resulted in several fundamental biological insights. In some cases understanding extreme phenotypes has also informed thinking about more prevalent metabolic diseases. Insulin resistance underpins the twin epidemics of obesity and type 2 diabetes as well as accounting for many of the metabolic problems encompassed by the term metabolic syndrome. This review provides a brief update on current understanding of human severe insulin resistance syndromes, before highlighting recent insights provided by studies in these rare syndromes into the molecular pathogenesis of elements of the metabolic syndrome.
authors.affiliation: Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, University of Cambridge, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Stears
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: Robert K
authors.initials: RK
authors.lastname: Semple
authors.forename: David B
authors.initials: DB
authors.lastname: Savage
mesh_terms: D000052:Acanthosis Nigricans / Q000175:diagnosis; D052242:Adiponectin / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D050171:Dyslipidemias / Q000175:diagnosis; D005234:Fatty Liver; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007003:Hypoglycemia / Q000175:diagnosis; D007333:Insulin Resistance / Q000235:genetics*; D050155:Lipogenesis / Q000502:physiology; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000503:physiopathology; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D052242:Adiponectin; D058539:Phosphatidylinositol 3-Kinase; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt