Searchable abstracts of presentations at key conferences in endocrinology

ea0020p187 | Endocrine tumours and neoplasia | ECE2009

Presence and potential pathophysiological relevance of GOAT, the ghrelin O-acylation enzyme, in human pituitary tumors

Quintero Ana , Martinez-Fuentes Antonio J , Dieguez Carlos , Benito-Lopez Pedro , Leal Alfonso , Webb Susan , Malagon Maria M , Luque Raul M , Castano Justo P

Ghrelin was isolated from stomach by its ability to stimulate growth hormone (GH) release through the GH-secretagogue receptor (GHS-R1a). However, ghrelin/GHS-R expression in multiple tissues and tumor types suggested additional roles for this tandem. Ghrelin, a 28-aminoacid peptide, requires a unique O-acylation at its Ser-3 residue to bind GHS-R1a and release GH. Conversely, unacylated ghrelin (UAG), initially considered inactive, seems to play distinct metabolic role...

ea0016p332 | Endocrine tumours | ECE2008

Ghrelin and its receptor are present in an ectopic ACTH lung neuroendocrine tumour causing Cushing's syndrome: potential pathophysiological implications

Quintero Ana , Martinez-Fuentes Antonio J , Gahete Manuel D , Vazquez-Martinez Rafael , Gutierrez-Alcantara Carmen , Jimenez-Reina Luis , Benito-Lopez Pedro , Malagon Maria M , Castano Justo P

Ghrelin is a 28-aa peptide originally isolated from stomach but present also in many tissues, including hypothalamus and pituitary, where it stimulates growth hormone (GH) release through the ghrelin/GH secretagogue receptor (GHS-R). Ghrelin also increases food intake and adiposity and could play a key integrative role in the endocrine–metabolic interface. Although its primary pituitary cell target are somatotropes, ghrelin also modulates other pituitary cell types, speci...

ea0016p463 | Neuroendocrinology | ECE2008

Identification and molecular characterization of new somatostatin receptor subtype 5 truncated isoforms in rodents

Cordoba-Chacon Jose , Luque Raul M , Gahete Manuel D , Duran-Prado Mario , Gracia-Navarro Francisco , Kineman Rhonda D , Malagon Maria M , Castano Justo P

The neuropeptide somatostatin (SRIF) exerts a wide variety of actions through five SRIF receptors (sst1-5). However, not all SRIF actions can be explained by activation of the known sst. In this context, our research group has identified two novel isoforms of sst subtype 5 (sst5A) named sst5B and sst5C expressed in human and pig. These isoforms are generated by splicing of cryptic introns within the coding sequence, which alters the open reading frame, and results in new, trun...

ea0056oc4.1 | Novel insights into prediabetes and type 2 diabetes | ECE2018

Dietary intervention modulates the expression of the splicing machinery in patients at high-risk of type 2 diabetes development: clinical implications

del Rio-Moreno Mercedes , Alors-Perez Emilia , Camargo Antonio , Delgado-Lista Javier , Lopez-Canovas Juan L. , Lopez-Miranda Jose , Luque Raul M. , Gahete Manuel D. , Castano Justo P.

Development of type-2 diabetes (T2D) is critically affected by the loss of phenotypic flexibility. There is emerging evidence suggesting that, under adverse metabolic conditions, alternative mRNA splicing is markedly dysregulated at different levels. For this reason, we hypothesized that such dysregulation could contribute to loss of phenotypic flexibility. Consequently, we aimed to explore whether changes in the splicing machinery in peripheral blood mononuclear cells (PBMCs)...

ea0056gp157 | Obesity | ECE2018

Obesity is associated with a dysregulation in the splicing machinery components at the hepatic level: influence of metformin

L-Lopez Fernando , Alors-Perez Emilia , del Rio-Moreno Mercedes , Sarmento-Cabral Andre , Castano Justo P , Luque Raul M , Gahete Manuel D

Obesity, a multifactorial chronic endocrine-metabolic disease, represents one of the most serious and complex global health threats, as it is commonly associated with multiple and severe comorbidities (e.g. diabetes type-2). Indeed, as a source of severe metabolic-dysregulation, obesity alters physiological, homeostatic gene expression patters in multiple metabolic-tissues, including the central metabolic hub, i.e. the liver. However, the precise molecular mechanisms underlyin...

ea0056p652 | Endocrine tumours and neoplasia | ECE2018

Metformin and Simvastatin: a therapeutic combination to reduce the aggressiveness of glioblastoma multiforme

Fuentes-Fayos Antonio C , Vazquez-Borrego Mari C , Mansfield Beth , Blanco-Acevedo Cristobal , Solivera Juan , Castano Justo P , Luque Raul M

Gliomas constitute the most frequent type of brain tumors and are characterized by a rapid growth and high diffusion through the brain. In particular, astrocytomas are a subtype of malignant gliomas that are graded from low to high aggressiveness (i.e. grade I, II, III and IV), being grade IV (glioblastoma multiforme, GBM) the most malignant type, and one of the most common cancers in the brain and CNS. To date, surgery is the first-line therapy combined with chemotherapy or r...

ea0056p785 | Pituitary - Basic | ECE2018

Treatment with antidiabetic biguanide drugs directly impacts the function of multiple pituitary cell types from two non-human primate models

Leon-Gonzalez Antonio J , Vazquez-Borrego Mari C , Fuentes-Fayos Antonio C , Gahete Manuel D , Castano Justo P , Kineman Rhonda D , Luque Raul M

Antidiabetic biguanides, such as metformin (the most commonly prescribed drug to treat type 2 diabetes) and phenformin, are synthetic insulin-sensitizing agents. In addition to their well-known anti-hyperglycemic actions, biguanides are being also studied in other medical disorders due to the beneficial effects that they exert in important pathologies, including cardiovascular disease or different types of cancer. Although some scattered studies have suggested that metformin c...

ea0075o09 | Obesity, metabolism & miscellaneous endocrinology | EYES2021

Characterization and oncogenic role of the somatostatin receptor splicing variant SST5TMD4 in human high-grade astrocytomas

Garcia-Garcia Miguel E. , Fuentes-Fayos Antonio C. , Peel Annabel , Blanco-Acevedo Cristobal , Solivera Juan , Castano Justo P. , Gahete Manuel D. , Luque Raul M.

Background: Gliomas are the most common primary brain tumor, being astrocytomas a subset of malignant gliomas graded on a scale of I to IV. Grade-IV astrocytomas (glioblastoma multiforme; GBM) are the most malignant and aggressive type. Current standard treatments are ineffective, being their average postoperative survival of 12-16 months. Therefore, there is a clear need for the identification of novel therapeutic targets to treat this pathology. In this context, the truncate...

ea0081oc6.6 | Oral Communications 6: Endocrine-Related Cancer | ECE2022

SF3B1 inhibition disrupts malignancy and prolongs survival in glioblastoma patients through BCL2L1-splicing and mTOR/ß-catenin pathways imbalances

G-Garcia Miguel E , Fuentes-Fayos Antonio C , Gomez Jesus Perez , Jimenez-Vacas Juan M , Blanco-Acevedo Cristobal , Sanchez-Sanchez Rafael , Solivera Juan , Breunig Joshua , Gahete Manuel D , Castano Justo P , Luque Raul M

Glioblastoma (GBM; grade IV astrocytoma) is one of the most devastating endocrine-related cancer worldwide based on its locally aggressive behavior and because it cannot be cured by current therapies. Therefore, the identification of novel diagnostic and prognostic biomarkers, and especially efficient therapeutic targets is urgently needed. In this sense, defects in alternative splicing process are associated with poor survival and high aggressiveness in cancer, including GBM....

ea0081p128 | Endocrine-Related Cancer | ECE2022

Splicing machinery dysregulation in rare neuroendocrine tumors: pheochromocytomas and paragangliomas

Trinidad Moreno Montilla Maria , Blazquez Encinas Rey Ricardo , Mario Martinez Montes Angel , Garcia Vioque Victor , Alors-Perez Emilia , Mangili Federica , Agraz-Doblas Antonio , Robledo Mercedes , Castano Justo P. , Ibanez Costa Alejandro

Pheochromocytomas and paragangliomas (PPGL) are commonly benign catecholamine-producing neuroendocrine tumors (NETs); however, up to 25 % of patients develop distant metastases or aggressive behavior. The current classification of PPGL comprises pseudohypoxia-profile, MAPK-pathway alteration, and Wnt-pathway dysregulation clusters according to their genomic characterization. However, to date, there are no biomarkers to help stratify patients based on their prognosis. Alternati...