Impaired insulin secretion in a mouse model of ataxia telangiectasia
| Autor: | Marc Latronica, Carrolee Barlow, Philip D.G. Miles, Kai Treuner, Jerrold M. Olefsky |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Aging medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Biology Diabetes Mellitus Experimental Pathogenesis Ataxia Telangiectasia Mice Insulin resistance Physiology (medical) Diabetes mellitus Internal medicine Glucose Intolerance Insulin Secretion medicine Animals Insulin Pancreatic hormone Mice Knockout Kinase Tumor Suppressor Proteins medicine.disease DNA-Binding Proteins Disease Models Animal Endocrinology Ataxia-telangiectasia Female Insulin Resistance |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 293:E70-E74 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | Ataxia telangiectasia (A-T) is an autosomal recessive disease caused by mutations in the A-T mutated (ATM) gene. The gene encodes a serine/threonine kinase with important roles in the cellular response to DNA damage, including the activation of cell cycle checkpoints and induction of apoptosis. Although these functions might explain the cancer predisposition of A-T patients, the molecular mechanisms leading to glucose intolerance and diabetes mellitus (DM) are unknown. We have investigated the pathogenesis of DM in a mouse model of A-T. Here we show that young Atm-deficient mice show normal fasting glucose levels and normal insulin sensitivity. However, oral glucose tolerance testing revealed delayed insulin secretion and resulting transient hyperglycemia. Aged Atm−/− mice show a pronounced increase in blood glucose levels and a decrease in insulin and C-peptide levels. Our findings support a role for ATM in metabolic function and point toward impaired insulin secretion as the primary cause of DM in A-T. |
| Databáze: | OpenAIRE |
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