Loss of arylformamidase with reduced thymidine kinase expression leads to impaired glucose tolerance
| العنوان: | Loss of arylformamidase with reduced thymidine kinase expression leads to impaired glucose tolerance |
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| المؤلفون: | Fay Probert, Tertius Hough, Roger D. Cox, I. Jane Cox, Gary Wall, Marianne Yon, Alison Hugill, Cheryl L. Scudamore, Liz Bentley, Michelle Stewart, Sara Wells |
| المصدر: | Biology Open, Vol 4, Iss 11, Pp 1367-1375 (2015) Biology Open |
| بيانات النشر: | The Company of Biologists, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | medicine.medical_specialty, QH301-705.5, Arylformamidase, Science, Inflammation, Type 2 diabetes, Biology, General Biochemistry, Genetics and Molecular Biology, Impaired glucose tolerance, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, medicine, Biology (General), Gene knockout, Kynurenine, 030304 developmental biology, 0303 health sciences, Insulin secretion, Diabetes, Tryptophan, medicine.disease, Phenotype, Endocrinology, Thymidine kinase, medicine.symptom, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Research Article |
| الوصف: | Tryptophan metabolites have been linked in observational studies with type 2 diabetes, cognitive disorders, inflammation and immune system regulation. A rate-limiting enzyme in tryptophan conversion is arylformamidase (Afmid), and a double knockout of this gene and thymidine kinase (Tk) has been reported to cause renal failure and abnormal immune system regulation. In order to further investigate possible links between abnormal tryptophan catabolism and diabetes and to examine the effect of single Afmid knockout, we have carried out metabolic phenotyping of an exon 2 Afmid gene knockout. These mice exhibit impaired glucose tolerance, although their insulin sensitivity is unchanged in comparison to wild-type animals. This phenotype results from a defect in glucose stimulated insulin secretion and these mice show reduced islet mass with age. No evidence of a renal phenotype was found, suggesting that this published phenotype resulted from loss of Tk expression in the double knockout. However, despite specifically removing only exon 2 of Afmid in our experiments we also observed some reduction of Tk expression, possibly due to a regulatory element in this region. In summary, our findings support a link between abnormal tryptophan metabolism and diabetes and highlight beta cell function for further mechanistic analysis. Summary: Mice homozygous for a tm1b deleted allele have impaired glucose tolerance due to reduced insulin secretion associated with reduced islet mass, but no evidence of renal disease, suggesting a link between abnormal tryptophan metabolism and diabetes. |
| اللغة: | English |
| تدمد: | 2046-6390 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::231e22eacf9264305029e688ebee359fTest http://bio.biologists.org/content/4/11/1367Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....231e22eacf9264305029e688ebee359f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20466390 |
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