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Reviews in Endocrine & Metabolic... Sep 2021Neuroendocrine neoplasms (NENs) comprise a broad spectrum of tumors with widely variable biological and clinical behavior. Primary tumor site, extent of disease, tumor... (Review)
Review
Neuroendocrine neoplasms (NENs) comprise a broad spectrum of tumors with widely variable biological and clinical behavior. Primary tumor site, extent of disease, tumor differentiation and expression of so matostatin receptors, proliferation and growth rates are the major prognostic factors that determine the therapeutic strategy. Treatment options for advanced disease have considerably expanded in recent years, particularly for well differentiated tumors (NETs). Novel drugs approved over the past decade in this context include somatostatin analogues and Lu-oxodotreotide for somatostatin-receptor-positive gastroenteropancreatic (GEP) NETs, sunitinib for pancreatic NETs (P-NETs), and everolimus for P-NETs and non-functioning lung or gastrointestinal NETs. Nevertheless, chemotherapy remains an essential component of the treatment armamentarium of patients with NENs, particularly of patients with P-NETs or those with bulky, symptomatic or rapidly progressive tumors (generally G3 or high-G2 NENs). In this manuscript we will comprehensively review available evidence related to the use of chemotherapy in lung and GEP NENs and will critically discuss its role in the treatment algorithm of this family of neoplasms.
Topics: Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms; Somatostatin; Stomach Neoplasms
PubMed: 33843007
DOI: 10.1007/s11154-021-09638-0 -
International Journal of Molecular... Feb 2023In recent years, there has been a significant increase in age-related diseases due to the improvement in life expectancy worldwide. The pancreas undergoes various... (Review)
Review
In recent years, there has been a significant increase in age-related diseases due to the improvement in life expectancy worldwide. The pancreas undergoes various morphological and pathological changes with aging, such as pancreatic atrophy, fatty degeneration, fibrosis, inflammatory cell infiltration, and exocrine pancreatic metaplasia. Meanwhile, these may predispose the individuals to aging-related diseases, such as diabetes, dyspepsia, pancreatic ductal adenocarcinoma, and pancreatitis, as the endocrine and exocrine functions of the pancreas are significantly affected by aging. Pancreatic senescence is associated with various underlying factors including genetic damage, DNA methylation, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and inflammation. This paper reviews the alternations of morphologies and functions in the aging pancreas, especially β-cells, closely related to insulin secretion. Finally, we summarize the mechanisms of pancreatic senescence to provide potential targets for treating pancreatic aging-related diseases.
Topics: Humans; Diabetes Mellitus; Pancreas; Pancreas, Exocrine; Pancreatic Diseases; Pancreatic Hormones; Pancreatic Neoplasms; Aging
PubMed: 36834922
DOI: 10.3390/ijms24043513 -
Journal of Diabetes and Its... 2016Glucagon-like peptide-1 (GLP-1) is originally identified in the gut as an incretin hormone, and it is potent in stimulating insulin secretion in the pancreas. However,... (Review)
Review
PURPOSE
Glucagon-like peptide-1 (GLP-1) is originally identified in the gut as an incretin hormone, and it is potent in stimulating insulin secretion in the pancreas. However, increasing evidence suggests that GLP-1 is also produced locally within pancreatic islets. This review focuses on the past and current discoveries regarding intra-islet GLP-1 production and its functions.
MAIN FINDINGS
There has been a long-standing debate with regard to whether GLP-1 is produced in the pancreatic α cells. Early controversies lead to the widely accepted conclusion that the vast majority of proglucagon is processed to form glucagon in the pancreas, whereas an insignificant amount is cleaved to produce GLP-1. With technological advancements, recent studies have shown that bioactive GLP-1 is produced locally in the pancreas, and the expression and secretion of GLP-1 within islets are regulated by various factors such as cytokines, hyperglycemia, and β cell injury.
CONCLUSIONS
GLP-1 is produced by the pancreatic α cells, and it is fully functional as an incretin. Therefore, intra-islet GLP-1 may exert insulinotropic and glucagonostatic effects locally via paracrine and/or autocrine actions, under both normal and diabetic conditions.
Topics: Glucagon; Glucagon-Like Peptide 1; Glucagon-Secreting Cells; Humans; Insulin; Insulin Secretion; Islets of Langerhans
PubMed: 27267264
DOI: 10.1016/j.jdiacomp.2016.05.016 -
Frontiers in Endocrinology 2022Neurotransmitters are signaling molecules secreted by neurons to coordinate communication and proper function among different sections in the central neural system (CNS)... (Review)
Review
Neurotransmitters are signaling molecules secreted by neurons to coordinate communication and proper function among different sections in the central neural system (CNS) by binding with different receptors. Some neurotransmitters as well as their receptors are found in pancreatic islets and are involved in the regulation of glucose homeostasis. Neurotransmitters can act with their receptors in pancreatic islets to stimulate or inhibit the secretion of insulin (β cell), glucagon (α cell) or somatostatin (δ cell). Neurotransmitter receptors are either G-protein coupled receptors or ligand-gated channels, their effects on blood glucose are mainly decided by the number and location of them in islets. Dysfunction of neurotransmitters receptors in islets is involved in the development of β cell dysfunction and type 2 diabetes (T2D).Therapies targeting different transmitter systems have great potential in the prevention and treatment of T2D and other metabolic diseases.
Topics: Diabetes Mellitus, Type 2; Glucagon; Glucagon-Secreting Cells; Humans; Insulin; Receptors, Neurotransmitter
PubMed: 35669692
DOI: 10.3389/fendo.2022.884549 -
Proceedings of the National Academy of... May 2023Iridoviridae, such as the lymphocystis disease virus-1 (LCDV-1) and other viruses, encode viral insulin-like peptides (VILPs) which are capable of triggering insulin...
Iridoviridae, such as the lymphocystis disease virus-1 (LCDV-1) and other viruses, encode viral insulin-like peptides (VILPs) which are capable of triggering insulin receptors (IRs) and insulin-like growth factor receptors. The homology of VILPs includes highly conserved disulfide bridges. However, the binding affinities to IRs were reported to be 200- to 500-fold less effective compared to the endogenous ligands. We therefore speculated that these peptides also have noninsulin functions. Here, we report that the LCDV-1 VILP can function as a potent and highly specific inhibitor of ferroptosis. Induction of cell death by the ferroptosis inducers erastin, RSL3, FIN56, and FINO2 and nonferroptotic necrosis produced by the thioredoxin-reductase inhibitor ferroptocide were potently prevented by LCDV-1, while human insulin had no effect. Fas-induced apoptosis, necroptosis, mitotane-induced cell death and growth hormone-releasing hormone antagonist-induced necrosis were unaffected, suggesting the specificity to ferroptosis inhibition by the LCDV-1 VILP. Mechanistically, we identified the viral C-peptide to be required for inhibition of lipid peroxidation and ferroptosis inhibition, while the human C-peptide exhibited no antiferroptotic properties. In addition, the deletion of the viral C-peptide abolishes radical trapping activity in cell-free systems. We conclude that iridoviridae, through the expression of insulin-like viral peptides, are capable of preventing ferroptosis. In analogy to the viral mitochondrial inhibitor of apoptosis and the viral inhibitor of RIP activation (vIRA) that prevents necroptosis, we rename the LCDV-1 VILP a viral peptide inhibitor of ferroptosis-1. Finally, our findings indicate that ferroptosis may function as a viral defense mechanism in lower organisms.
Topics: Humans; Insulin; C-Peptide; Apoptosis; Necrosis; Cell Death
PubMed: 37186845
DOI: 10.1073/pnas.2300320120 -
Frontiers in Endocrinology 2023Fatty acids and glucose are key biomolecules that share several commonalities including serving as energy substrates and as signaling molecules. Fatty acids can be... (Review)
Review
Fatty acids and glucose are key biomolecules that share several commonalities including serving as energy substrates and as signaling molecules. Fatty acids can be synthesized endogenously from intermediates of glucose catabolism via de-novo lipogenesis. Bile acids are synthesized endogenously in the liver from the biologically important lipid molecule, cholesterol. Evidence abounds that fatty acids and bile acids play direct and indirect roles in systemic glucose homeostasis. The tight control of plasma glucose levels during postprandial and fasted states is principally mediated by two pancreatic hormones, insulin and glucagon. Here, we summarize experimental studies on the endocrine effects of fatty acids and bile acids, with emphasis on their ability to regulate the release of key hormones that regulate glucose metabolism. We categorize the heterogenous family of fatty acids into short chain fatty acids (SCFAs), unsaturated, and saturated fatty acids, and highlight that along with bile acids, these biomolecules regulate glucose homeostasis by serving as endogenous ligands for specific G-protein coupled receptors (GPCRs). Activation of these GPCRs affects the release of incretin hormones by enteroendocrine cells and/or the secretion of insulin, glucagon, and somatostatin by pancreatic islets, all of which regulate systemic glucose homeostasis. We deduce that signaling induced by fatty acids and bile acids is necessary to maintain euglycemia to prevent metabolic diseases such as type-2 diabetes and related metabolic disorders.
Topics: Fatty Acids; Glucagon; Bile Acids and Salts; Receptors, G-Protein-Coupled; Insulin; Glucose; Homeostasis
PubMed: 37484954
DOI: 10.3389/fendo.2023.1206063 -
Endokrynologia Polska 2023Not required for Clinical Vignette.
Not required for Clinical Vignette.
Topics: Humans; Hypoglycemia; Autoimmune Diseases; Insulins; Insulin
PubMed: 37994588
DOI: 10.5603/ep.95669 -
Andes Pediatrica : Revista Chilena de... Jun 2023Insulin therapy is complex in pediatric patients because they present greater variations in insulin requirements. Traditional insulins have limitations related to time... (Review)
Review
Insulin therapy is complex in pediatric patients because they present greater variations in insulin requirements. Traditional insulins have limitations related to time of onset of action and duration of effect, which has led to the development of new insulins, seeking to reduce chronic complications, severe or nocturnal hypoglycemia, and to improve adherence to therapy. This review updates the information on new insulins, their mechanisms of action and the benefits they provide in the treatment of diabetes. Insulin analogues attempt to mimic the physiological secretion of the hormone, including time of action and duration of effect. The most used prandial analogs are the so-called rapid-acting insulins, including Faster Aspartic and the new basal insulins, glargine U300 and degludec, which have a prolonged action of more than 24 hours and therefore require a daily dose. New technologies under development include biosimilar insulins such as the glargine biosimilar, already available in the clinic. New formulations are being developed for the future, as well as novel ways of dispersing them, mimicking the action of pancreatic cells, which will allow a more physiological and personalized management of the disease.
Topics: Humans; Child; Diabetes Mellitus, Type 1; Insulin Glargine; Biosimilar Pharmaceuticals; Insulin; Insulins
PubMed: 37909930
DOI: 10.32641/andespediatr.v94i3.4477 -
Cell Stem Cell Apr 2023Understanding the origin of pancreatic β cells has profound implications for regenerative therapies in diabetes. For over a century, it was widely held that adult...
Understanding the origin of pancreatic β cells has profound implications for regenerative therapies in diabetes. For over a century, it was widely held that adult pancreatic duct cells act as endocrine progenitors, but lineage-tracing experiments challenged this dogma. Gribben et al. recently used two existing lineage-tracing models and single-cell RNA sequencing to conclude that adult pancreatic ducts contain endocrine progenitors that differentiate to insulin-expressing β cells at a physiologically important rate. We now offer an alternative interpretation of these experiments. Our data indicate that the two Cre lines that were used directly label adult islet somatostatin-producing ∂ cells, which precludes their use to assess whether β cells originate from duct cells. Furthermore, many labeled ∂ cells, which have an elongated neuron-like shape, were likely misclassified as β cells because insulin-somatostatin coimmunolocalizations were not used. We conclude that most evidence so far indicates that endocrine and exocrine lineage borders are rarely crossed in the adult pancreas.
Topics: Insulin-Secreting Cells; Evidence Gaps; Cell Differentiation; Pancreas; Pancreatic Ducts; Insulin; Somatostatin
PubMed: 37028408
DOI: 10.1016/j.stem.2023.03.003 -
BMC Pediatrics Apr 2023The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), accountable for Coronavirus disease 2019 (COVID-19), may cause hyperglycemia and additional systemic... (Observational Study)
Observational Study
BACKGROUND
The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), accountable for Coronavirus disease 2019 (COVID-19), may cause hyperglycemia and additional systemic complexity in metabolic parameters. It is unsure even if the virus itself causes type 1 or type 2 diabetes mellitus (T1DM or T2DM). Furthermore, it is still unclear whether even recuperating COVID-19 individuals have an increased chance to develop new-onset diabetes.
METHODS
We wanted to determine the impact of COVID-19 on the levels of adipokines, pancreatic hormones, incretins and cytokines in acute COVID-19, convalescent COVID-19 and control children through an observational study. We performed a multiplex immune assay analysis and compared the plasma levels of adipocytokines, pancreatic hormones, incretins and cytokines of children presenting with acute COVID-19 infection and convalescent COVID-19.
RESULTS
Acute COVID-19 children had significantly elevated levels of adipsin, leptin, insulin, C-peptide, glucagon and ghrelin in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had elevated levels of adipsin, leptin, insulin, C-peptide, glucagon, ghrelin and Glucagon-like peptide-1 (GLP-1) in comparison to control children. On the other hand, acute COVID-19 children had significantly decreased levels of adiponectin and Gastric Inhibitory Peptide (GIP) in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had decreased levels of adiponectin and GIP in comparison to control children. Acute COVID-19 children had significantly elevated levels of cytokines, (Interferon (IFN)) IFNγ, Interleukins (IL)-2, TNFα, IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12, IL-17A and Granulocyte-Colony Stimulating Factors (G-CSF) in comparison to convalescent COVID-19 and controls. Convalescent COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12, IL-17A and G-CSF in comparison to control children. Additionally, Principal component Analysis (PCA) analysis distinguishes acute COVID-19 from convalescent COVID-19 and controls. The adipokines exhibited a significant correlation with the levels of pro-inflammatory cytokines.
CONCLUSION
Children with acute COVID-19 show significant glycometabolic impairment and exaggerated cytokine responses, which is different from convalescent COVID-19 infection and controls.
Topics: Humans; Child; Incretins; Adipokines; Leptin; Ghrelin; Tumor Necrosis Factor-alpha; Complement Factor D; Interleukin-17; Pancreatic Hormones; Diabetes Mellitus, Type 2; Adiponectin; Glucagon; Interleukin-6; C-Peptide; COVID-19; SARS-CoV-2; Cytokines; Interleukin-12; Granulocyte Colony-Stimulating Factor
PubMed: 37013538
DOI: 10.1186/s12887-023-03971-w