Endocrine Abstracts

Mutations in the ACTH receptor (Melanocortin 2 receptor/MC2R) are associated with Familial Glucocorticoid Deficiency/FGD. FGD is an autosomal recessive disorder that results from ACTH insensitivity at the adrenal cortex. However, only about 25% of FGD are caused by mutations in the MC2R suggesting the genetically heterogeneous nature of the disease. The transfection-mediated functional expression of the MC2R can only be achieved in cell lines of adrenal origin implying that th...

Orexins, acting via their receptors, are involved in the control of feeding, sleep-wakefulness, arousal, neuroendocrine homeostasis and autonomic regulation. However, the 5′ structure and regulation of human orexin type 2 receptor (OX2R) gene remains is not known. We present original findings regarding the 5′ structural organization of the human OX2R gene and identify four OX2R mRNA transcripts that differ in their 5′-untranslated region (UTR). The four trans...

Background and aim: Orexin-A (OXA) increases insulin secretion and inhibits glucagon secretion, suggesting a role in regulating glucose homeostasis. The effects of OXA on pancreatic A-cells on the cellular level have not yet been demonstrated. Aim of our study was therefore to characterise the underlying signal transduction pathways and to study the OXA effects on proglucagon gene transcription.Methods: The effects of OXA on glucagon secretion were evalu...

The family of urocortins (UCNs) exert important pathophysiological actions in the control of peripheral homeostatic mechanisms, through activation of the type 2-corticotropin releasing hormone receptor (CRH-R2). This G-protein coupled receptor preferentially binds urocortins (UCN, UCNII and UCNIII) than CRH. In most tissues, CRH-R2 activation leads to increased cAMP production. In this study we used HEK293 cells stably overexpressing recombinant CRH-R2β receptors to inves...

Somatostatin (SS) is a widely distributed polypeptide that exerts inhibitory effects on hormone secretion and cell proliferation by interacting with five different receptors (SST1-SST5), that display important differences in tissue distribution, coupling to second messengers, affinity for SS and intracellular trafficking. SS analogues currently used in the treatment of acromegaly inhibit hormone secretion and cell proliferation by binding to SST2 and 5. Beta-arrestins have bee...

Objectives: Somatostatin (SST) inhibits insulin secretion from pancreatic B-cells through a reduction of intracellular free calcium ([Ca2+]i). The influx of Ca2+ is mediated by voltage-operated Ca2+ channels (VOCCs). The role of VOCCs of the R-type (CaV2.3) in SST-mediated processes is unknown. Therefore, we designed a study to identify SST-receptor subtypes (SSTR) in insulinoma cells (INS-1) and characterize the role of t...

Reorganization of the actin cytoskeleton could coincide with the activation of several seven transmembrane receptors (7TM receptors) (1). Stimulation of Rho family members leads to rapid remodeling of the actin cytoskeleton and subsequent stress fiber formation and certain 7TM receptors were shown to induce Rho-dependent responses via heterotrimeric G-proteins. Gα12, Gα13 as well as Gαq/11 can link 7TM receptors to RhoA activatio...