Endocrine Abstracts

RCTs and real-life studies have shown the efficacy of GLP-1 RAs on weight loss, glycemic outcomes, and prevention of cardiovascular (CV) events, but long-term data are lacking. This was a retrospective cohort study of 253 patients with a first prescription of a GLP-1 RA between 2009 and 2016 and a minimum follow-up of 5 years. The endpoints of the study were weight and glycemic outcomes. Secondary endpoints were the occurrence of renal and CV events, comparing patients with GL...

Neuroendocrine tumors (NETs) are rare neoplasms showing a wide spectrum of clinical behaviors. The therapeutic options available for NET treatment are rarely curative and most are palliative, as NETs frequently show resistance to pharmacological therapy. Cancers develop in complex tissue environments, which they depend upon for sustained growth, invasion and metastasis. A major characteristic of the tumor microenvironment is inflammatory cell infiltration, where tumor-associat...

Metformin (1.1-dimethylbiguanide hydrochloride), a widely used antidiabetic drug, has been reported to display potent anticancer properties in various types of cancers, including neuroendocrine tumors. Recently, a potential synergistic activity between metformin and octreotide (SSA) in Pancreatic Neuroendocrine Tumors (P-NETs) has been proposed. AIP (aryl hydrocarbon receptor-interacting protein) acts as tumor suppressor gene in neuroendocrine tumors at pituitary level and it ...

Gastric carcinoids secondary to autoimmune atrophic gastritis (GC type 1) are usually well differentiated neoplasia, with an indolent course and an excellent overall prognosis. However, a subset of these tumors (<5%) may develop advanced disease, with lymph node and/or hepatic metastasis. The pathogenesis of these carcinoids is related to chronic trophic stimuli to enterochromaffin-like (ECL) cells due to chronic hypergastrinemia. Treatments directed to remove the source o...

Somatostatin exerts its inhibitory effects on hormone secretion and cell proliferation via five receptors subtypes (SST1-SST5). After agonist binding, receptor residues mainly located in the carboxyl terminal (CT) and in the third intracellular loop (IC3) are phosphorylated and β-arrestins are recruited to drive SSTRs internalization.Aim of the study is to characterize the intracellular mechanisms responsible for SST2 internalization and identify th...

Neuroendocrine neoplasms (NENs) are rare tumour showing a wide spectrum of clinical behaviours. Therapeutic options available for NET treatment are rarely curative and mostly palliative, as NETs frequently show resistance to pharmacological therapy. Cancers develop in complex tissue environments, which they depend on. Tumour-associated macrophages (TAMs) are a major cellular component of the tumour microenvironment. Two polarized state of macrophages are described in literatur...

cAMP is implicated in the inhibition or stimulation of proliferation depending on cell type. The activation of cAMP–PKA pathway generates proliferative signals in GH-secreting adenomas whereas this effect is not present, or even opposite, in non-functioning pituitary cells (NFPA). Although cAMP effects were initially attributed to PKA activation, recently the discovery of two cAMP-activated guanine nucleotide exchange factors (Epac1,2) was proposed as a novel mechanism fo...

In this study we employed a novel bioluminescence resonance energy transfer (BRET) biosensor to study the coupling specificity of somatostatin receptor 5 (SST5) and its naturally occurring mutant R240W in living cells. Our previous data demonstrated that SST5 carrying the R240W mutation as well as other mutations in the third intracellular loop maintained the ability to inhibit intracellular cAMP levels similarly to the wild-type but failed to mediate the inhibition of intrace...

Dopamine agonists (DA) inhibit prolactin (PRL) secretion and expression on the pituitary lactotrophs by binding dopamine D2 receptor. Prolactinomas are the most common secreting pituitary adenomas, and DA are the first choice for their treatment because they reduce PRL levels and tumor size. However, a subset of patients is resistant to DA. The mechanisms involved in DA resistance are not fully understood, although decreased expression of D2 receptor or altered signal transduc...

Background: Aberrant cAMP signalling is involved in the pathogenesis of somatotropinomas. Recently, variants of phosphodiesterase type 11A (PDE11A) gene have been described in patients with adrenocortical tumors. Aim of the study was to investigate the presence of these variants in patients with somatotropinomas.Subjects and methods: Germ-line DNA of 78 acromegalic patients was screened for known genetic variants of PDE11A by direct sequencing or restric...