-
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 -
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 -
The Journal of Endocrinology Aug 2023Glucagon is the principal glucose-elevating hormone that forms the first-line defence against hypoglycaemia. Along with insulin, glucagon also plays a key role in... (Review)
Review
Glucagon is the principal glucose-elevating hormone that forms the first-line defence against hypoglycaemia. Along with insulin, glucagon also plays a key role in maintaining systemic glucose homeostasis. The cells that secrete glucagon, pancreatic α-cells, are electrically excitable cells and use electrical activity to couple its hormone secretion to changes in ambient glucose levels. Exactly how glucose regulates α-cells has been a topic of debate for decades but it is clear that electrical signals generated by the cells play an important role in glucagon secretory response. Decades of studies have already revealed the key players involved in the generation of these electrical signals and possible mechanisms controlling them to tune glucagon release. This has offered the opportunity to fully understand the enigmatic α-cell physiology. In this review, we describe the current knowledge on cellular electrophysiology and factors regulating excitability, glucose sensing, and glucagon secretion. We also discuss α-cell pathophysiology and the perspective of addressing glucagon secretory defects in diabetes for developing better diabetes treatment, which bears the hope of eliminating hypoglycaemia as a clinical problem in diabetes care.
Topics: Humans; Glucagon; Glucagon-Secreting Cells; Insulin; Glucose; Diabetes Mellitus; Hypoglycemia; Cell Physiological Phenomena; Electrophysiology
PubMed: 37159865
DOI: 10.1530/JOE-22-0295 -
Annals of the New York Academy of... Jul 2021Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet β cell loss and dysfunction resulting in insulin deficiency and hyperglycemia.... (Review)
Review
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet β cell loss and dysfunction resulting in insulin deficiency and hyperglycemia. During a presymptomatic phase of established β cell autoimmunity, β cell loss may first be evident through assessment of β cell secretory capacity, a measure of functional β cell mass. Reduction in pancreatic islet β cell reserve eventually manifests as impaired first-phase insulin response to glucose and abnormal glucose tolerance, which progresses until the functional capacity for β cell secretion can no longer meet the demand for insulin to control glycemia. A functional β cell mass of ∼25% of normal may be required to avoid symptomatic T1D but is already associated with dysregulated glucagon secretion. With symptomatic T1D, stimulated C-peptide levels >0.60 ng/mL (0.200 pmol/mL) indicate the presence of clinically meaningful residual β cell function for contributing to glycemic control, although even higher residual C-peptide appears necessary for evidencing glucose-dependent islet β and α cell function that may contribute to maintaining (near)normal glycemia. β cell replacement by islet transplantation can restore a physiologic reserve capacity for insulin secretion, confirming thresholds for functional β cell mass required for independence from insulin therapy.
Topics: Diabetes Mellitus, Type 1; Glucagon; Glucose; Humans; Hyperglycemia; Insulin; Insulin Secretion; Insulin-Secreting Cells
PubMed: 33550589
DOI: 10.1111/nyas.14572 -
Journal of Molecular Medicine (Berlin,... Apr 2020The pancreatic islet is a dense cellular network comprised of several cell types with endocrine function vital in the control of glucose homeostasis, metabolism, and... (Review)
Review
The pancreatic islet is a dense cellular network comprised of several cell types with endocrine function vital in the control of glucose homeostasis, metabolism, and feeding behavior. Within the islet, endocrine hormones also form an intricate paracrine network with supportive cells (endothelial, neuronal, immune) and secondary signaling molecules regulating cellular function and survival. Modulation of these signals has potential consequences for diabetes development, progression, and therapeutic intervention. Beta cell loss, reduced endogenous insulin secretion, and dysregulated glucagon secretion are hallmark features of both type 1 and 2 diabetes that not only impact systemic regulation of glucose, but also contribute to the function and survival of cells within the islet. Advancing research and technology have revealed new islet biology (cellular identity and transcriptomes) and identified previously unrecognized paracrine signals and mechanisms (somatostatin and ghrelin paracrine actions), while shifting prior views of intraislet communication. This review will summarize the paracrine signals regulating islet endocrine function and survival, the disruption and dysfunction that occur in diabetes, and potential therapeutic targets to preserve beta cell mass and function.
Topics: Animals; Cell Survival; Ghrelin; Glucagon-Secreting Cells; Glucose; Glycogen; Humans; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Pancreatic Polypeptide; Paracrine Communication; Signal Transduction; Somatostatin; Somatostatin-Secreting Cells
PubMed: 32067063
DOI: 10.1007/s00109-020-01887-x -
Canadian Journal of Diabetes Jun 2022The coronavirus-2019 (COVID-19) pandemic has had significant impact on research directions and productivity in the past 2 years. Despite these challenges, since 2020,... (Review)
Review
The coronavirus-2019 (COVID-19) pandemic has had significant impact on research directions and productivity in the past 2 years. Despite these challenges, since 2020, more than 2,500 peer-reviewed articles have been published on pancreatic islet biology. These include updates on the roles of isocitrate dehydrogenase, pyruvate kinase and incretin hormones in insulin secretion, as well as the discovery of inceptor and signalling by circulating RNAs. The year 2020 also brought advancements in in vivo and in vitro models, including a new transgenic mouse for assessing beta-cell proliferation, a "pancreas-on-a-chip" to study glucose-stimulated insulin secretion and successful genetic editing of primary human islet cells. Islet biologists evaluated the functionality of stem-cell-derived islet-like cells coated with semipermeable biomaterials to prevent autoimmune attack, revealing the importance of cell maturation after transplantation. Prompted by observations that COVID-19 symptoms can worsen for people with obesity or diabetes, researchers examined how islets are directly affected by severe acute respiratory syndrome coronavirus 2. Herein, we highlight novel functional insights, technologies and therapeutic approaches that emerged between March 2020 and July 2021, written for both scientific and lay audiences. We also include a response to these advancements from patient stakeholders, to help lend a broader perspective to developments and challenges in islet research.
Topics: Animals; Biology; COVID-19; Diabetes Mellitus, Type 1; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Mice
PubMed: 35589534
DOI: 10.1016/j.jcjd.2021.11.002 -
American Society of Clinical Oncology... May 2023Neuroendocrine neoplasms (NENs) comprise a beautifully complicated, exciting landscape of histologies and clinical behaviors. However, the nuanced complexity of low- and... (Review)
Review
Neuroendocrine neoplasms (NENs) comprise a beautifully complicated, exciting landscape of histologies and clinical behaviors. However, the nuanced complexity of low- and high-grade variants can easily overwhelm both patients and providers. In this chapter, we review the ever-expanding literature on both functioning and nonfunctioning small bowel and pancreatic NENs, touching on somatostatin analogs, hepatic-directed therapies, small molecules, radiopharmaceuticals, immunotherapy, cytotoxic chemotherapy, and new promising agents. Furthermore, we suggest some strategies to address the most challenging scenarios seen in clinical practice, including sequencing of agents, treatment of carcinoid syndrome, and options for well-differentiated high-grade disease.
Topics: Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Somatostatin; Radiopharmaceuticals
PubMed: 37257140
DOI: 10.1200/EDBK_389278 -
Diabetes Sep 2022Glucagon and insulin are the main regulators of blood glucose. While the actions of insulin are extensively mapped, less is known about glucagon. Besides glucagon's role... (Review)
Review
Glucagon and insulin are the main regulators of blood glucose. While the actions of insulin are extensively mapped, less is known about glucagon. Besides glucagon's role in glucose homeostasis, there are additional links between the pancreatic α-cells and the hepatocytes, often collectively referred to as the liver-α-cell axis, that may be of importance for health and disease. Thus, glucagon receptor antagonism (pharmacological or genetic), which disrupts the liver-α-cell axis, results not only in lower fasting glucose but also in reduced amino acid turnover and dyslipidemia. Here, we review the actions of glucagon on glucose homeostasis, amino acid catabolism, and lipid metabolism in the context of the liver-α-cell axis. The concept of glucagon resistance is also discussed, and we argue that the various elements of the liver-α-cell axis may be differentially affected in metabolic diseases such as diabetes, obesity, and nonalcoholic fatty liver disease (NAFLD). This conceptual rethinking of glucagon biology may explain why patients with type 2 diabetes have hyperglucagonemia and how NAFLD disrupts the liver-α-cell axis, compromising the normal glucagon-mediated enhancement of substrate-induced amino acid turnover and possibly fatty acid β-oxidation. In contrast to amino acid catabolism, glucagon-induced glucose production may not be affected by NAFLD, explaining the diabetogenic effect of NAFLD-associated hyperglucagonemia. Consideration of the liver-α-cell axis is essential to understanding the complex pathophysiology underlying diabetes and other metabolic diseases.
Topics: Amino Acids; Blood Glucose; Diabetes Mellitus, Type 2; Glucagon; Glucose; Hepatocytes; Humans; Insulin; Non-alcoholic Fatty Liver Disease
PubMed: 35657688
DOI: 10.2337/dbi22-0004 -
Translational Psychiatry Feb 2021Dopamine (DA) and norepinephrine (NE) are catecholamines primarily studied in the central nervous system that also act in the pancreas as peripheral regulators of...
Dopamine (DA) and norepinephrine (NE) are catecholamines primarily studied in the central nervous system that also act in the pancreas as peripheral regulators of metabolism. Pancreatic catecholamine signaling has also been increasingly implicated as a mechanism responsible for the metabolic disturbances produced by antipsychotic drugs (APDs). Critically, however, the mechanisms by which catecholamines modulate pancreatic hormone release are not completely understood. We show that human and mouse pancreatic α- and β-cells express the catecholamine biosynthetic and signaling machinery, and that α-cells synthesize DA de novo. This locally-produced pancreatic DA signals via both α- and β-cell adrenergic and dopaminergic receptors with different affinities to regulate glucagon and insulin release. Significantly, we show DA functions as a biased agonist at α-adrenergic receptors, preferentially signaling via the canonical G protein-mediated pathway. Our findings highlight the interplay between DA and NE signaling as a novel form of regulation to modulate pancreatic hormone release. Lastly, pharmacological blockade of DA D-like receptors in human islets with APDs significantly raises insulin and glucagon release. This offers a new mechanism where APDs act directly on islet α- and β-cell targets to produce metabolic disturbances.
Topics: Adrenergic Agents; Dopamine; Glucagon; Insulin; Insulin Secretion; Norepinephrine; Pancreas
PubMed: 33589583
DOI: 10.1038/s41398-020-01171-z