Glucose Homeostasis in Mice Is Transglutaminase 2 Independent
| العنوان: | Glucose Homeostasis in Mice Is Transglutaminase 2 Independent |
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| المؤلفون: | Robert M. Graham, Sara R. Holman, Gregory J. Cooney, Kristy Jackson, James G. Burchfield, Carsten Schmitz-Peiffer, Aimee Davenport, Mark Aplin, Trevor J. Biden, Ting W. Yiu, Chris J. Mitchell, Siiri E. Iismaa, Liam O’Reilly, James Cantley |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 5, p e63346 (2013) |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Blood Glucose, Mouse, medicine.medical_treatment, lcsh:Medicine, Biochemistry, Mice, Endocrinology, 0302 clinical medicine, Insulin-Secreting Cells, Molecular Cell Biology, Homeostasis, Insulin, Signaling in Cellular Processes, Glucose homeostasis, lcsh:Science, Mice, Knockout, 2. Zero hunger, 0303 health sciences, Glucose tolerance test, Multidisciplinary, medicine.diagnostic_test, Animal Models, medicine.anatomical_structure, Medicine, Research Article, Signal Transduction, medicine.medical_specialty, Genotype, Clinical Research Design, Blood sugar, Carbohydrate metabolism, Biology, Glucose Signaling, Maturity onset diabetes of the young, Islets of Langerhans, 03 medical and health sciences, Model Organisms, GTP-Binding Proteins, Internal medicine, Diabetes mellitus, Diabetes Mellitus, Genetics, medicine, Animals, Protein Glutamine gamma Glutamyltransferase 2, Animal Models of Disease, 030304 developmental biology, Diabetic Endocrinology, Transglutaminases, Pancreatic islets, lcsh:R, Glucose Tolerance Test, Diabetes Mellitus Type 2, medicine.disease, Mice, Inbred C57BL, Glucose, Metabolism, Metabolic Disorders, lcsh:Q, Gene Function, Gene Deletion, 030217 neurology & neurosurgery |
| الوصف: | Transglutaminase type 2 (TG2) has been reported to be a candidate gene for maturity onset diabetes of the young (MODY) because three different mutations that impair TG2 transamidase activity have been found in 3 families with MODY. TG2 null (TG2(-/-)) mice have been reported to be glucose intolerant and have impaired glucose-stimulated insulin secretion (GSIS). Here we rigorously evaluated the role of TG2 in glucose metabolism using independently generated murine models of genetic TG2 disruption, which show no compensatory enhanced expression of other TGs in pancreatic islets or other tissues. First, we subjected chow- or fat-fed congenic SV129 or C57BL/6 wild type (WT) and TG2(-/-) littermates, to oral glucose gavage. Blood glucose and serum insulin levels were similar for both genotypes. Pancreatic islets isolated from these animals and analysed in vitro for GSIS and cholinergic potentiation of GSIS, showed no significant difference between genotypes. Results from intraperitoneal glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) were similar for both genotypes. Second, we directly investigated the role of TG2 transamidase activity in insulin secretion using a coisogenic model that expresses a mutant form of TG2 (TG2(R579A)), which is constitutively active for transamidase activity. Intraperitoneal GTTs and ITTs revealed no significant differences between WT and TG2(R579A/R579A) mice. Given that neither deletion nor constitutive activation of TG2 transamidase activity altered basal responses, or responses to a glucose or insulin challenge, our data indicate that glucose homeostasis in mice is TG2 independent, and question a link between TG2 and diabetes. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::40490f077ebe646546f396c353317725 https://doi.org/10.1371/journal.pone.0063346 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....40490f077ebe646546f396c353317725 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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