دورية أكاديمية
Contrasting Diabetes Phenotypes Associated with Hepatocyte Nuclear Factor-1α and -1β Mutations
| العنوان: | Contrasting Diabetes Phenotypes Associated with Hepatocyte Nuclear Factor-1α and -1β Mutations |
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| المؤلفون: | Pearson, Ewan R., Badman, Michael K., Lockwood, Christopher R., Clark, Penelope M., Ellard, Sian, Bingham, Coralie, Hattersley, Andrew T. |
| المصدر: | Pearson , E R , Badman , M K , Lockwood , C R , Clark , P M , Ellard , S , Bingham , C & Hattersley , A T 2004 , ' Contrasting Diabetes Phenotypes Associated with Hepatocyte Nuclear Factor-1α and -1β Mutations ' , Diabetes Care , vol. 27 , no. 5 , pp. 1102-1107 . https://doi.org/10.2337/diacare.27.5.1102Test |
| سنة النشر: | 2004 |
| المجموعة: | Discovery - University of Dundee Online Publications |
| مصطلحات موضوعية: | FPG, fasting plasma glucose, HNF, hepatocyte nuclear factor, HOMA, homeostasis model assessment, IDE, insulin-degrading enzyme, IVGTT, intravenous glucose tolerance test, MODY, maturity-onset diabetes of the young, PEAKglu, acute insulin response to glucose, PEAKtolb, acute insulin response to tolbutamide, /dk/atira/pure/subjectarea/asjc/2700/2724, name=Internal Medicine, /dk/atira/pure/subjectarea/asjc/2700/2712, name=Endocrinology, Diabetes and Metabolism, /dk/atira/pure/subjectarea/asjc/2900/2902, name=Advanced and Specialised Nursing |
| الوصف: | Objective : Mutations in the highly homologous transcription factors hepatocyte nuclear factor (HNF)-1α and -1β cause maturity-onset diabetes of the young types 3 and 5, respectively. Diabetes due to HNF-1α mutations is well characterized. However, physiological assessment of the HNF-1β phenotype is limited. We aimed to test the hypothesis that the diabetes phenotype due to HNF-1β mutations is similar to that in HNF-1α. Research Design and Methods : Fasting biochemistry and a tolbutamide-modified intravenous glucose tolerance test (IVGTT) were compared in matched HNF-1β, HNF-1α, type 2 diabetic, and control subjects. Homeostasis model assessment indexes were determined from fasting insulin and glucose. The peak measures for the insulin increment after tolbutamide and for the insulin increment after glucose were determined from the IVGTT. Results : The HNF-1β patients showed a 2.4-fold reduction in insulin sensitivity compared with the HNF-1α patients (P = 0.001) with fasting insulin concentrations 2.7-fold higher (P = 0.004). HNF-1β patients had lower HDL cholesterol (1.17 vs. 1.46 mmol/l; P = 0.009) and higher triglyceride (2.2 vs. 1.35 mmol/l; P = 0.015) levels than HNF-1α patients. The HNF-1β patients had similar β-cell responses to tolbutamide and glucose as the type 2 diabetic patients, but in the HNF-1α patients, the tolbutamide response was considerably increased relative to the response to glucose (P = 0.002). Conclusions : HNF-1β patients have a different diabetes phenotype than HNF-1α patients. Those with HNF-1β mutations have hyperinsulinemia and associated dyslipidemia consistent with insulin resistance and may have a different β-cell defect. This suggests that despite considerable homology and a shared binding site, HNF-1α and HNF-1β have a different role in maintaining normal glucose homeostasis. This result suggests a new etiological pathway for insulin resistance involving HNF-1β. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://discovery.dundee.ac.uk/en/publications/5354a503-9f21-4652-bce0-c842f07c6e12Test |
| DOI: | 10.2337/diacare.27.5.1102 |
| الإتاحة: | https://doi.org/10.2337/diacare.27.5.1102Test https://discovery.dundee.ac.uk/en/publications/5354a503-9f21-4652-bce0-c842f07c6e12Test http://www.scopus.com/inward/record.url?scp=2342472176&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.3AD04EE0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/diacare.27.5.1102 |
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