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Finding a Target
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
There are three forms of signalling mediated by secreted molecules: paracrine, synaptic, and endocrine. Signalling molecules secreted by cells to act as local mediators, which only effect cells in the immediate environment, must not be allowed to diffuse too far, so are rapidly taken up by the neighbouring cells, or destroyed by extracellular enzymes, or immobilised by the extracellular matrix. This is called paracrine signalling. For multicellular organisms to be able to coordinate cell behaviour across the entire organism, some signalling molecules must travel far afield to distant cells. This is achieved in two ways: by networks of nerve cells and by the action of hormones. Synaptic signalling involves routes of neurones along which electrochemical impulses travel to stimulate the release of chemical signals called neurotransmitter, which carry the signal on between neurones across gaps called synaptic junctions and propagate the electrochemical impulse in the adjoining neurone. Endocrine cells release hormones, which are signalling molecules that travel in the bloodstream of an animal (or sap in plants) and thus distribute widely throughout the body, enabling signals to be carried to distant cells. Since this process relies on diffusion, it is much slower than synaptic signalling.
Basic medicine: physiology
Published in Roy Palmer, Diana Wetherill, Medicine for Lawyers, 2020
The pancreas contains both endocrine and exocrine tissue. Endocrine cells, which are found in clusters or islets, secrete the hormones insulin and glucagon, both of which affect glucose metabolism. Lack of insulin results in diabetes, a condition characterized by glycosuria (glucose in the urine), polyuria (excessive micturition) and weight loss. Pancreatic exocrine cells synthesize several different digestive enzymes.
General Aspects of Endocrine Physiology
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
The peptide hormones are synthesized by mRNA transcription in the nucleus, leading to ribosomal translation with the production of the polypeptide within the endoplasmic reticulum. The polypeptide is concentrated in the Golgi apparatus and then stored in storage granules. Large protein hormones are usually retained in the storage granules, whereas small peptide hormones are bound to specific binding proteins within the granules (Figure 59.1). The hormones are released from the endocrine cell by exocytosis following a neural, chemical, hormonal or physical stimulus. Hormones not released are usually degraded to amino acids and recycled.
GABA treatment does not induce neogenesis of new endocrine cells from pancreatic ductal cells
Published in Islets, 2023
Shihao Wang, Xin Dong, Mahan Maazi, Nan Chen, Amarpreet Mahil, Janel L. Kopp
A few studies have suggested that ductal cells can give rise to endocrine cells during homeostasis.7,26 Here we show that, similar to our previous studies,20 we do not see neogenesis of beta cells from Sox9+ ductal cells. Importantly, this was true in the context of two distinct Sox9CreER founder lines that have different recombination efficiencies in the large ducts, but similarly high recombination in small ducts. Both of our characterized and published founder lines efficiently label centroacinar and terminal ducts. The more efficient 34.1 Sox9CreER mouse model also targets large ducts more effectively and this could underlie the ability of this model to induce main duct intraductal papillary mucinous neoplasia in KrasG12D-expressing ductal cells with reduced Pten expression.22 Overall, our data support the conclusion that wild-type adult ductal cells do not give rise to other cell types during homeostasis.
Determinants and dynamics of pancreatic islet architecture
Published in Islets, 2022
Glucose homeostasis in vertebrates is made possible by the islets of Langerhans. These small clusters of endocrine cells reside in the pancreas, surrounded by exocrine tissue. In contrast to the exocrine tissue, which secretes digestive enzymes into the gut through the pancreatic duct system, the islets of Langerhans secrete endocrine hormones into the blood. Through four decades of research, it has become clear that islets are not just unstructured endocrine cell aggregates but rather highly organized micro-organs. They have species-specific three-dimensional architecture, which is critical to their proper function in response to nutritional stimuli. Islet architecture facilitates endocrine cell polarity and connection with the microvasculature to guarantee secretion of insulin into the capillaries, physical and electrical cell-cell coupling to assure synchronous hormone secretion, and directionality of intra-islet paracrine signaling and connection with the nervous system for feedback regulation.1–4 Islet architecture is disrupted in all types of diabetes mellitus.5,6 It is also disrupted in cadaveric islets during isolation and culture prior to islet transplantation as well as after infusion into the portal vein, limiting transplantation outcomes.7–9 Moreover, recapitulating native islet architecture remains a key challenge for in vitro generation of islets from stem cells.10
The role of SCAMP5 in central nervous system diseases
Published in Neurological Research, 2022
Ye Chen, Jiali Fan, Dongqiong Xiao, Xihong Li
In mammals, neurons, endocrine cells and exocrine cells all secrete proteins along the secretory pathway [17]. Genetics and in vitro experiments have revealed the molecular mechanism of exocytosis from neurons and from endocrine and exocrine cells. Innate immunity and adaptive immunity are regulated by cytokines, especially cytokines secreted by macrophages [18,19]. The membrane transport process during exocytosis and endocytosis is regulated by the SCAMP E peptide [20]. Previous studies on SCAMPs have mostly focused on the regulation of exocytosis during LDCV secretion or TGN vesicle transport. For example, SCAMP1 can promote the expansion and closure of fusion pores and participate in the regulation of LDCV secretion [21,22]. SCAMP2 interacts with phospholipase D1 and phosphatidylinositol diphosphate (PIP2) through its E peptide to regulate the formation of fusion pores during LDCV exocytosis [23].