Arsenic exposure and calpain-10 polymorphisms impair the function of pancreatic beta-cells in humans: a pilot study of risk factors for T2DM
| العنوان: | Arsenic exposure and calpain-10 polymorphisms impair the function of pancreatic beta-cells in humans: a pilot study of risk factors for T2DM |
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| المؤلفون: | A. Jay Gandolfi, Patricia Ostrosky-Wegman, Raúl U. Hernández-Ramírez, Monserrat Sordo, Marcia Hiriart, Gonzalo G. García-Vargas, Susana Bassol, Laura Cruz, Andrea Díaz-Villaseñor, Arturo Cebrián, Walter T. Klimecki, Lizbeth López-Carillo, Mariano E. Cebrián |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 1, p e51642 (2013) |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Mitochondrial Diseases, endocrine system diseases, Epidemiology, medicine.medical_treatment, lcsh:Medicine, Pilot Projects, Type 2 diabetes, 010501 environmental sciences, Toxicology, 01 natural sciences, Endocrinology, Risk Factors, Insulin-Secreting Cells, Insulin Secretion, Insulin, lcsh:Science, 0303 health sciences, Multidisciplinary, Calpain, Environmental exposure, Middle Aged, 3. Good health, Genetic Epidemiology, Medicine, Environmental Pollutants, Female, Research Article, Adult, medicine.medical_specialty, Genotype, Toxic Agents, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Arsenic, 03 medical and health sciences, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Genetics, Humans, Risk factor, 030304 developmental biology, 0105 earth and related environmental sciences, Aged, Diabetic Endocrinology, Population Biology, lcsh:R, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Human Genetics, Environmental Exposure, Diabetes Mellitus Type 2, medicine.disease, Biomarker Epidemiology, Diabetes Mellitus and Deafness, Diabetes Mellitus, Type 2, Genetic Polymorphism, lcsh:Q, Insulin Resistance, Population Genetics |
| الوصف: | The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs) through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function) and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2) in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2a87a742792b23d7e73b2d476b61548Test https://pubmed.ncbi.nlm.nih.gov/23349674Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b2a87a742792b23d7e73b2d476b61548 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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