ECE2016 Oral Communications Diabetes prediction & complications (5 abstracts)
Identification of a spliceosome-associated fingerprint with potential to predict development of type 2 diabetes in high-risk patients
Raúl M. Luque 1 , Manuel D. Gahete 1 , Mercedes del Rio-Moreno 1 , Sergio Pedraza-Arévalo 1 , Antonio Camargo 2 , Javier Delgado-Lista 2 , Francisco Gracia-Navarro 1 , Francisco Pérez-Jiménez 2 , José López-Miranda 2 & Justo P. Castaño 1
1Department of Cell Biology, Physiology and Immunology, University of Córdoba (UCO), Hospital Universitario Reina Sofía (HURS), Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), CIBE, Córdoba, Spain; 2Lipids and Atherosclerosis Unit, IMIBIC, HURS, UCO and CIBERobn, Córdoba, Spain.
Prevalence of metabolic syndrome (MetS) and type-2 Diabetes (T2D) is growing dramatically worldwide. Loss of phenotypic flexibility, i.e. the difficulty to cope with different stressors to maintain metabolic homeostasis, contributes critically to the development of MetS/T2DM. Thus, it is essential to identify the key modifiers of phenotypic plasticity that define an individual’s susceptibility to develop T2DM. In this scenario, emerging evidence indicates that, under adverse metabolic conditions, the splicing machinery is markedly dysregulated in many tissues. We hypothesized that such a dysregulation could contribute to loss of phenotypic flexibility, and, as gene expression pattern in PBMCs commonly reflects disease-characteristic expression patterns, we reasoned that changes in spliceosome components of PBMCs might serve as biosensor/early indicators of MetS/T2D. To test this notion, expression of selected components of the major (n=13) and minor spliceosome (n=4), and associated splicing factors (n=28) was evaluated in PBMCs from 40 patients, who were initially non-T2D but in high-risk to develop T2D, and had suffered a prior cardiovascular event (CORDIOPREV study). Actually, during the 3-year follow-up, 20 individuals developed T2D and 20 did not (controls). PBMCs were isolated from basal and 4-h post-prandial blood, at the inclusion in the study and after 3-years. Results revealed that initial expression of relevant splicing factors and spliceosome components was altered in PBMCs from individuals who subsequently developed T2D. However, the most remarkable changes were observed during the post-prandial response, wherein expression of several splicing factors (e.g. Magoh, SRSF2, SRSF4, Tra2beta) was drastically induced in T2D-developing individuals compared to control patients, not developing T2D after 3-years of follow-up. These results reveal the existence of pre-TD2 development-associated spliceosome alterations, which could be related to the loss of phenotypic flexibility, and could help to predict, as a “splicing fingerprint”, development of T2D in high-risk patients.
Volume 41
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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