Endocrine Abstracts

Ghrelin has been classically known as a GH- and metabolism-regulating hormone, mainly produced by stomach. However, it also acts as a paracrine or autocrine factor in several tissues, where it can regulate tissue growth and neoplastic cell proliferation. Of note, ghrelin needs to be acylated at Ser3 by the ghrelin-O-acyltransferase (GOAT) enzyme to bind to its receptor GHS-R1a. Interestingly, the ghrelin gene can give rise to distinct additional peptides, generated by alternat...

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...

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...

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)...

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...

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...

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...

Hepatocellular carcinoma (HCC) is an aggressive tumour frequently associated to an underlying chronic liver disease. In this sense, metabolic dysfunction-associated steatotic liver disease (MASLD) is considered as a growing cause of HCC development. Considering the need of novel therapeutic approaches, and the promising data about targeting the tumour microenvironment in cancer, we performed quantitative proteomics on HCC samples to characterize the components and regulators o...

Obesity (OB) and type-2 diabetes (T2D) are chronic endocrine-metabolic diseases, associated to insulin-resistance (IR), that represent capital health problems. Fortunately, both pathologies are, at least, partially reversible by dietary interventions, but the potential metabolic, molecular, cellular factors and mechanisms that might be involved in the total/partial reversion of OB/IR/T2D by dietary interventions are poorly known. Thus, in this work, we aimed evaluate the impac...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the main hepatic manifestation of obesity. MASLD was recently defined as liver steatosis in the presence of at least one cardiometabolic risk factor and reduced or absent alcohol intake. MASLD prevalence is rapidly increasing, thus becoming the fastest growing aetiology of the most common primary liver cancer, hepatocellular carcinoma (HCC), and the leading cause of liver transplantation in HCC patients. Curre...