Human obesity and insulin resistance: lessons from experiments of nature.
Examination of individuals with 'extreme phenotypes' has revealed some rare monogenic disorders that were previously unknown. This identification can shed light on physiological pathways that are also important in normal physiology and how their impairment leads to more common, milder, multigenic forms of the disease. Ultimately, this is a potential route to treatment of both disease types. This approach is discussed in relation to Type 2 diabetes, arising from both insufficient insulin production and insulin resistance.
O'Rahilly
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Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. so104@medschl.cam.ac.uk
D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000628:therapy; D020022:Genetic Predisposition to Disease; D006801:Humans; D007328:Insulin / Q000172:deficiency; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D008659:Metabolic Diseases / Q000378:metabolism; D008954:Models, Biological; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism
D007328:Insulin; D020738:Leptin; D047495:PPAR gamma; D044105:Receptor, Melanocortin, Type 4