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Peptides Jan 2023Century old glucagon is a classic pancreatic hormone. But today we also know that the glucagon gene is expressed at high levels at extrapancreatic sites - particularly... (Review)
Review
Century old glucagon is a classic pancreatic hormone. But today we also know that the glucagon gene is expressed at high levels at extrapancreatic sites - particularly so in the gut. Major hormonal glucagon gene products in the digestive tract are the two glucagon-like peptides (GLP-1 and -2). Of these, truncated GLP-1 has in recent decades attracted massive interest due to its incretin effect, and the subsequent GLP-1 derived design of potent diabetes and obesity drugs. Truncated GLP-1 has consequently become an important contributor to gastrointestinal endocrinology. The gastrointestinal branch of endocrinology today includes more than 100 bioactive peptides encoded by some 30 different hormone genes. Therefore, the gut is the largest endocrine organ in the body. In addition to a general discussion of glucagon peptides in the hierarchy of gut hormones, this review also includes three short notes about glucagon studies from the 1970s. These studies dealt with reactive hypoglycemia, chronic liver disease, and the secretory response of pancreatic glucagon to gastrin/cholecystokinin stimulation. Considering today's possibilities in molecular endocrinology, revisits to the questions raised by these studies might be worthwhile.
Topics: Glucagon; Peptides; Glucagon-Like Peptide 1; Gastrointestinal Hormones; Incretins
PubMed: 36521797
DOI: 10.1016/j.peptides.2022.170924 -
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 -
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 -
Current Opinion in Gastroenterology Sep 2020To provide an overview of mediators involved in the pathogenesis of postacute pancreatitis diabetes mellitus. (Review)
Review
PURPOSE OF REVIEW
To provide an overview of mediators involved in the pathogenesis of postacute pancreatitis diabetes mellitus.
RECENT FINDINGS
The 'holistic prevention of pancreatitis' framework has brought to the fore the sequelae of not only end-stage chronic pancreatitis and extensive pancreatic necrosis but also mild acute pancreatitis. Insights from the DORADO project have provided a wealth of information on the signalling molecules that do and do not affect glucose metabolism in individuals after mild acute pancreatitis and have challenged conventional views of the pathogenesis of postpancreatitis diabetes mellitus.
SUMMARY
Growing evidence compels a reconsideration of the dogma that mechanical β-cell destruction (and the resulting insulin deficiency) is the only underlying mechanism of postpancreatitis diabetes mellitus. Chronic low-grade inflammation, β-cell compensation, lipolysis, altered secretion of gut hormones, and changes in iron metabolism characterize postacute pancreatitis diabetes mellitus. Some of these are druggable targets that offer novel opportunities to reduce the burden of pancreatitis through tertiary prevention.
Topics: Acute Disease; Diabetes Mellitus; Humans; Insulin; Pancreatitis
PubMed: 32618612
DOI: 10.1097/MOG.0000000000000654 -
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 -
Clinical Advances in Hematology &... Sep 2021Neuroendocrine tumors (NETs) are a heterogeneous group of epithelial neoplasms with predominantly neural and endocrine differentiation that have the ability to produce... (Review)
Review
Neuroendocrine tumors (NETs) are a heterogeneous group of epithelial neoplasms with predominantly neural and endocrine differentiation that have the ability to produce peptide hormones and other biologically active substances. The histologic characterization of NETs based on differentiation and grading is crucial to determining prognosis and treatment. Surgery still offers the best chance of cure for patients with NETs, and tumor resection is the preferred approach when possible. For locally advanced or metastatic disease, approaches to treatment can vary widely depending on the extent of disease and goals of therapy. A better understanding of the biology of NETs acquired over the last decade has facilitated the development of targeted therapies, such as everolimus and a variety of tyrosine kinase inhibitors. Furthermore, the field of theranostics has led to dramatic improvements in our diagnostic and treatment abilities. Chemotherapy has a role in the treatment of NETs, evidenced by the benefit shown with the combination of temozolomide and capecitabine to treat pancreatic NETs. Somatostatin analogues are a mainstay of treatment because they reduce secretory products and have antiproliferative effects on NET cells. In this work, we aim to review the landscape for the diagnosis and treatment of well-differentiated NETs.
Topics: Antineoplastic Agents; Capecitabine; Everolimus; Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Somatostatin
PubMed: 34495022
DOI: No ID Found -
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 -
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 -
Endocrinology Nov 2020Glucose homeostasis is maintained in large part due to the actions of the pancreatic islet hormones insulin and glucagon, secreted from β- and α-cells, respectively.... (Review)
Review
Glucose homeostasis is maintained in large part due to the actions of the pancreatic islet hormones insulin and glucagon, secreted from β- and α-cells, respectively. The historical narrative positions these hormones in opposition, with insulin primarily responsible for glucose-lowering and glucagon-driving elevations in glucose. Recent progress in this area has revealed a more complex relationship between insulin and glucagon, highlighted by data demonstrating that α-cell input is essential for β-cell function and glucose homeostasis. Moreover, the common perception that glucagon levels decrease following a nutrient challenge is largely shaped by the inhibitory effects of glucose administration alone on the α-cell. Largely overlooked is that a mixed nutrient challenge, which is more representative of typical human feeding, actually stimulates glucagon secretion. Thus, postprandial metabolism is associated with elevations, not decreases, in α-cell activity. This review discusses the recent advances in our understanding of how α-cells regulate metabolism, with a particular focus on the postprandial state. We highlight α- to β-cell communication, a term that describes how α-cell input into β-cells is a critical axis that regulates insulin secretion and glucose homeostasis. Finally, we discuss the open questions that have the potential to advance this field and continue to evolve our understanding of the role that α-cells play in postprandial metabolism.
Topics: Animals; Blood Glucose; Eating; Energy Metabolism; Glucagon; Glucagon-Secreting Cells; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Postprandial Period
PubMed: 32964214
DOI: 10.1210/endocr/bqaa169 -
Nutrients Apr 2022This review addresses the fasting vs. re-feeding effects of retinoic acid (RA) biosynthesis and functions, and sexually dimorphic RA actions. It also discusses other... (Review)
Review
This review addresses the fasting vs. re-feeding effects of retinoic acid (RA) biosynthesis and functions, and sexually dimorphic RA actions. It also discusses other understudied topics essential for understanding RA activities-especially interactions with energy-balance-regulating hormones, including insulin and glucagon, and sex hormones. This report will introduce RA homeostasis and hormesis to provide context. Essential context also will encompass RA effects on adiposity, muscle function and pancreatic islet development and maintenance. These comments provide background for explaining interactions among insulin, glucagon and cortisol with RA homeostasis and function. One aim would clarify the often apparent RA contradictions related to pancreagenesis vs. pancreas hormone functions. The discussion also will explore the adverse effects of RA on estrogen action, in contrast to the enhancing effects of estrogen on RA action, the adverse effects of androgens on RA receptors, and the RA induction of androgen biosynthesis.
Topics: Estrogens; Glucagon; Insulin; Receptors, Retinoic Acid; Tretinoin
PubMed: 35458115
DOI: 10.3390/nu14081553