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Diabetologia Oct 2020Pancreatic beta cells are the only cell type in our body capable of producing and secreting insulin to instruct the insulin-sensitive cells and tissues of our bodies to... (Review)
Review
Pancreatic beta cells are the only cell type in our body capable of producing and secreting insulin to instruct the insulin-sensitive cells and tissues of our bodies to absorb nutrients after a meal. Accurate control of insulin release is of critical importance; too little insulin leads to diabetes, while an excess of insulin can cause potentially fatal hypoglycaemia. Yet, the pancreas of most people will control insulin secretion safely and effectively over decades and in response to glucose excursions driven by tens of thousands of meals. Because we only become aware of the important contributions of the pancreas when it fails to maintain glucose homeostasis, it is easy to forget just how well insulin release from a healthy pancreas is matched to insulin need to ensure stable blood glucose levels. Beta cells achieve this feat by extensive crosstalk with the rest of the endocrine cell types in the islet, notably the glucagon-producing alpha cells and somatostatin-producing delta cells. Here I will review the important paracrine contributions that each of these cells makes to the stimulation and subsequent inhibition of insulin release in response to a transient nutrient stimulation, and make the case that a breakdown of this local crosstalk contributes to the pathophysiology of diabetes. Graphical abstract.
Topics: Acetylcholine; Autocrine Communication; Corticotropin-Releasing Hormone; Glucagon; Glucagon-Like Peptide 1; Glucagon-Secreting Cells; Humans; Insulin Secretion; Insulin-Secreting Cells; Paracrine Communication; Serotonin; Somatostatin; Somatostatin-Secreting Cells; Urocortins; gamma-Aminobutyric Acid
PubMed: 32894316
DOI: 10.1007/s00125-020-05213-5 -
Journal of Cellular Physiology Nov 2018Heart failure (HF) remains a major cause of morbidity and mortality worldwide. The primary cause identified for HF is impaired left ventricular myocardial function, and... (Review)
Review
Heart failure (HF) remains a major cause of morbidity and mortality worldwide. The primary cause identified for HF is impaired left ventricular myocardial function, and clinical manifestations may lead to severe conditions like pulmonary congestion, splanchnic congestion, and peripheral edema. Development of new therapeutic strategies remains the need of the hour for controlling the problem of HF worldwide. Deeper insights into the molecular mechanisms involved in etiopathology of HF indicate the significant role of calcium signaling, autocrine signaling pathways, and insulin-like growth factor-1 signaling that regulates the physiologic functions of heart growth and development such as contraction, metabolism, hypertrophy, cytokine signaling, and apoptosis. In view of these facts, a transcription factor (TF) regulating the myriad of these signaling pathways may prove as a lead candidate for development of therapeutics. Adenovirus E4 promoter-binding protein (E4BP4), also known as nuclear-factor, interleukin 3 regulated (NFIL3), a type of basic leucine zipper TF, is known to regulate the signaling processes involved in the functioning of heart. The current review discusses about the expression, structure, and functional role of E4BP4 in signaling processes with emphasis on calcium signaling mechanisms, autocrine signaling, and insulin-like growth factor II receptor-mediated processes regulated by E4BP4 that may regulate the pathogenesis of HF. We propose that E4BP4, being the critical component for the regulation of the above signaling processes, may serve as a novel therapeutic target for HF, and scientific investigations are merited in this direction.
Topics: Apoptosis; Autocrine Communication; Basic-Leucine Zipper Transcription Factors; Calcium Signaling; DNA-Binding Proteins; Gene Expression Regulation; Heart Failure; Humans; Insulin-Like Growth Factor I; Promoter Regions, Genetic; Transcription Factors
PubMed: 29856483
DOI: 10.1002/jcp.26790 -
Microvascular Research Mar 2021Vascular calcification, a common pathological basis of vascular disease, is caused by various diseases and is an independent risk factor for cardiovascular events.... (Review)
Review
Vascular calcification, a common pathological basis of vascular disease, is caused by various diseases and is an independent risk factor for cardiovascular events. Therefore, elucidating the pathogenesis of vascular calcification has significant clinical benefits. It is generally believed that vascular calcification is similar to the processes of bone development and cartilage formation. The transformation of vascular smooth muscle cells into osteoblast- and chondrocyte-like cells is a key event. However, recent studies have found that under certain conditions, endothelial cells participate in vascular calcification via endothelial-mesenchymal transition, cytokine secretion, extracellular vesicle synthesis, angiogenesis regulation and hemodynamics. This review aims to explore the relationship between endothelial cells and vascular calcification and to provide a theoretical basis and new ideas for the active prevention and treatment of vascular calcification in the clinic.
Topics: Animals; Autocrine Communication; Cellular Microenvironment; Endothelial Cells; Endothelium, Vascular; Epithelial-Mesenchymal Transition; Extracellular Vesicles; Hemodynamics; Humans; Mechanotransduction, Cellular; Neovascularization, Pathologic; Paracrine Communication; Vascular Calcification
PubMed: 33189731
DOI: 10.1016/j.mvr.2020.104105 -
Development (Cambridge, England) Feb 2022The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and...
The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (HH) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a previously unreported autocrine function of HH signaling in airway epithelial cells. Epithelial cell depletion of the ligand sonic hedgehog (SHH) or its effector smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, HH signaling inhibition also hampers cell proliferation and differentiation. Epithelial HH function is mediated, at least in part, through transcriptional activation, as HH signaling inhibition leads to downregulation of cell type-specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.
Topics: Animals; Autocrine Communication; Cell Differentiation; Cell Proliferation; Cells, Cultured; Down-Regulation; Embryo, Mammalian; Epithelial Cells; Hedgehog Proteins; Humans; Lung; Mice; Mice, Knockout; Signal Transduction; Smoothened Receptor; Trachea; Transcription Factors
PubMed: 35112129
DOI: 10.1242/dev.199804 -
Trends in Cell Biology Apr 2016'Secrete-and-sense cells' can communicate by secreting a signaling molecule while also producing a receptor that detects the molecule. The cell can potentially 'talk' to... (Review)
Review
'Secrete-and-sense cells' can communicate by secreting a signaling molecule while also producing a receptor that detects the molecule. The cell can potentially 'talk' to itself ('self-communication') or talk to neighboring cells with the same receptor ('neighbor communication'). The predominant forms of secrete-and-sense cells are self-communicating 'autocrine cells', which are largely found in animals, and neighbor-communicating 'quorum sensing cells', which are mostly associated with bacteria. While assumed to function independently of one another, recent studies have discovered quorum-sensing organs and autocrine-signaling microbes. Moreover, similar types of genetic circuit control many autocrine and quorum-sensing cells. Here, we outline these recent findings and explain how autocrine and quorum sensing are two sides of a many-sided 'dice' created by the versatile secrete-and-sense cell.
Topics: Acyl-Butyrolactones; Animals; Ants; Autocrine Communication; Bacteria; Cell Proliferation; Feedback, Physiological; Gene Expression Regulation; Humans; Intercellular Signaling Peptides and Proteins; Quorum Sensing; Receptors, Cell Surface; Signal Transduction; T-Lymphocytes
PubMed: 26671200
DOI: 10.1016/j.tcb.2015.11.002 -
Biomolecules May 2021Organ fibrosis is a common pathological result of various chronic diseases with multiple causes. Fibrosis is characterized by the excessive deposition of extracellular... (Review)
Review
Organ fibrosis is a common pathological result of various chronic diseases with multiple causes. Fibrosis is characterized by the excessive deposition of extracellular matrix and eventually leads to the destruction of the tissue structure and impaired organ function. Prostaglandins are produced by arachidonic acid through cyclooxygenases and various prostaglandin-specific synthases. Prostaglandins bind to homologous receptors on adjacent tissue cells in an autocrine or paracrine manner and participate in the regulation of a series of physiological or pathological processes, including fibrosis. This review summarizes the properties, synthesis, and degradation of various prostaglandins, as well as the roles of these prostaglandins and their receptors in fibrosis in multiple models to reveal the clinical significance of prostaglandins and their receptors in the treatment of fibrosis.
Topics: Animals; Autocrine Communication; Chronic Disease; Fibrosis; Humans; Paracrine Communication; Prostaglandin-Endoperoxide Synthases; Prostaglandins
PubMed: 34073892
DOI: 10.3390/biom11060789 -
Seminars in Cell & Developmental Biology Nov 2019In mammals, new neurons can be generated from neural stem cells in specific regions of the adult brain. Neural stem cells are characterized by their abilities to... (Review)
Review
In mammals, new neurons can be generated from neural stem cells in specific regions of the adult brain. Neural stem cells are characterized by their abilities to differentiate into all neural lineages and to self-renew. The specific microenvironments regulating neural stem cells, commonly referred to as neurogenic niches, comprise multiple cell populations whose precise contributions are under active current exploration. Understanding the cross-talk between neural stem cells and their niche components is essential for the development of therapies against neurological disorders in which neural stem cells function is altered. In this review, we describe and discuss recent studies that identified novel components in the neural stem cell niche. These discoveries bring new concepts to the field. Here, we evaluate these recent advances that change our understanding of the neural stem cell niche heterogeneity and its influence on neural stem cell function.
Topics: Animals; Autocrine Communication; Cerebrospinal Fluid; Humans; Neural Stem Cells; Neurons; Signal Transduction; Stem Cell Niche
PubMed: 30639325
DOI: 10.1016/j.semcdb.2019.01.005 -
American Journal of Physiology.... Oct 2014One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the... (Review)
Review
One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the pituitary-bone axis has become one of the major topics in skeletal physiology. Here, we discuss the relevant evidence about the posterior pituitary hormone oxytocin (OT), previously thought to exclusively regulate parturition and breastfeeding, which has recently been established to directly regulate bone mass. Both osteoblasts and osteoclasts express OT receptors (OTR), whose stimulation enhances bone mass. Consistent with this, mice deficient in OT or OTR display profoundly impaired bone formation. In contrast, bone resorption remains unaffected in OT deficiency because, even while OT stimulates the genesis of osteoclasts, it inhibits their resorptive function. Furthermore, in addition to its origin from the pituitary, OT is also produced by bone marrow osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. In turn, the power of estrogen to increase bone mass is OTR-dependent. Therefore, OTR(-/-) mice injected with 17β-estradiol do not show any effects on bone formation parameters, while the same treatment increases bone mass in wild-type mice. These findings together provide evidence for an anabolic action of OT in regulating bone mass and suggest that bone marrow OT may enhance the bone-forming action of estrogen through an autocrine circuit. This established new physiological role for OT in the maintenance of skeletal integrity further suggests the potential use of this hormone for the treatment of osteoporosis.
Topics: Animals; Autocrine Communication; Bone and Bones; Estradiol; Humans; Mice; Mice, Knockout; Models, Animal; Osteoblasts; Osteoclasts; Osteogenesis; Oxytocin; Receptors, Oxytocin
PubMed: 25209411
DOI: 10.1152/ajpregu.00040.2014 -
American Journal of Physiology.... Jan 2021Insulin secretion by β-cells is largely controlled by circulating nutrients, hormones, and neurotransmitters. However, recent years have witnessed the multiplication of... (Review)
Review
Insulin secretion by β-cells is largely controlled by circulating nutrients, hormones, and neurotransmitters. However, recent years have witnessed the multiplication of studies investigating whether local regulation also takes place within pancreatic islets, in which β-cells cohabit with several other cell types. The cell composition and architectural organization of human islets differ from those of rodent islets and are particularly favorable to cellular interactions. An impressive number of hormonal (glucagon, glucagon-like peptide-1, somatostatin, etc.) and nonhormonal products (ATP, acetylcholine, γ-aminobutyric acid, dopamine, etc.) are released by islet cells and have been implicated in a local control of insulin secretion. This review analyzes reports directly testing paracrine and autocrine control of insulin secretion in isolated human islets. Many of these studies were designed on background information collected in rodent islets. However, the perspective of the review is not to highlight species similarities or specificities but to contrast established and speculative mechanisms in human islets. It will be shown that the current evidence is convincing only for a minority of candidates for a paracrine function whereas arguments supporting a physiological role of others do not stand up to scrutiny. Several pending questions await further investigation.
Topics: Autocrine Communication; Hormones; Humans; Insulin Secretion; Islets of Langerhans; Paracrine Communication
PubMed: 33103455
DOI: 10.1152/ajpendo.00485.2020 -
Platelets Sep 2018Platelets serotonin (5-hydroxytrytamine, 5-HT) uptake and storage in dense granules is tightly regulated by the serotonergic transport system in the blood. Several 5-HT... (Review)
Review
Platelets serotonin (5-hydroxytrytamine, 5-HT) uptake and storage in dense granules is tightly regulated by the serotonergic transport system in the blood. Several 5-HT transporters (5-HTTs) have been identified in the vasculature and blood cells, beyond them 5-HTT is the major 5-HT transporter in platelets. Abnormal 5-HT concentrations in the blood plasma or increased platelet 5-HT uptake or abnormal release contribute to the development of various diseases in the vasculature. Consequently, several clinical trials suggested the positive therapeutic effects of 5-HTT blockade in the circulation. Inhibition of 5-HT strongly attenuates autocrine and paracrine functions of platelets, influencing platelet aggregation, vascular contraction, permeability, tissue repair, wound healing, immunity and cancer. Here, we highlight the current state of basic biological research regarding the hemostatic and non-hemostatic functions of platelet-derived 5-HT in normal and disease conditions. We also describe the physiological consequences of targeting platelet 5-HT functions in thrombosis, stroke, inflammation and cancer to overcome common health problems.
Topics: Autocrine Communication; Blood Platelets; Humans; Paracrine Communication; Serotonin
PubMed: 29863942
DOI: 10.1080/09537104.2018.1478072