Digenic inheritance of severe insulin resistance in a human pedigree
| Autor: | David B. Savage, Gudrun Ihrke, Maria A. Soos, E. Louise Thomas, K. Meeran, Inês Barroso, Antonio Vidal-Puig, Aline Meirhaeghe, Maura Agostini, Jian'an Luan, Odelia Rajanayagam, Jimmy D. Bell, Stephen O'Rahilly, Dirk Berger, Richard J. Ross, Anne-Helen Harding, Alan J. Schafer, Mark Gurnell, Nicholas J. Wareham, V. Krishna K. Chatterjee, Stella George |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Heterozygote medicine.medical_specialty Peroxisome proliferator-activated receptor gamma medicine.medical_treatment Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor CHO Cells Type 2 diabetes Biology Frameshift mutation Insulin resistance Cricetinae Protein Phosphatase 1 Internal medicine Phosphoprotein Phosphatases Genetics medicine Animals Humans Frameshift Mutation Gene Aged chemistry.chemical_classification Insulin Lipid metabolism Middle Aged medicine.disease Recombinant Proteins Pedigree DNA-Binding Proteins Endocrinology Diabetes Mellitus Type 2 chemistry Female Insulin Resistance Transcription Factors |
| Zdroj: | Nature Genetics. 31:379-384 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng926 |
| Popis: | Impaired insulin action is a key feature of type 2 diabetes and is also found, to a more extreme degree, in familial syndromes of insulin resistance. Although inherited susceptibility to insulin resistance may involve the interplay of several genetic loci, no clear examples of interactions among genes have yet been reported. Here we describe a family in which five individuals with severe insulin resistance, but no unaffected family members, were doubly [corrected] heterozygous with respect to frameshift/premature stop mutations in two unlinked genes, PPARG and PPP1R3A these encode peroxisome proliferator activated receptor gamma, which is highly expressed in adipocytes, and protein phosphatase 1, regulatory subunit 3, the muscle-specific regulatory subunit of protein phosphatase 1, which are centrally involved in the regulation of carbohydrate and lipid metabolism, respectively. That mutant molecules primarily involved in either carbohydrate or lipid metabolism can combine to produce a phenotype of extreme insulin resistance provides a model of interactions among genes that may underlie common human metabolic disorders such as type 2 diabetes. |
| Databáze: | OpenAIRE |
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