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Current Diabetes Reviews 2020Type 2 Diabetes (T2D) is a major health problem worldwide. This metabolic disease is indicated by high blood glucose levels due to insufficient insulin production by the... (Review)
Review
INTRODUCTION
Type 2 Diabetes (T2D) is a major health problem worldwide. This metabolic disease is indicated by high blood glucose levels due to insufficient insulin production by the pancreas. An inflammatory response occurs as a result of the immune response to high blood glucose levels as well as the presence of inflammatory mediators produced by adipocytes and macrophages in fat tissue. This low and chronic inflammation damages the pancreatic beta cells and leads to insufficient insulin production, which results in hyperglycemia. Hyperglycemia in diabetes is thought to cause dysfunction of the immune response, which fails to control the spread of invading pathogens in diabetic subjects. Therefore, diabetic subjects are known to more susceptible to infections. The increased prevalence of T2D will increase the incidence of infectious diseases and related comorbidities.
OBJECTIVE
This review provides an overview of the immunological aspect of T2D and the possible mechanisms that result in increased infections in diabetics.
CONCLUSION
A better understanding of how immune dysfunctions occur during hyperglycemia can lead to novel treatments and preventions for infectious diseases and T2D comorbidities, thus improving the outcome of infectious disease treatment in T2D patients.
Topics: Chronic Disease; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Immune System; Infections; Inflammation; Insulin; Insulin-Secreting Cells
PubMed: 31657690
DOI: 10.2174/1573399815666191024085838 -
Arquivos de Gastroenterologia 2020Fat infiltration in the pancreas is called pancreatic steatosis and it has several synonyms such as pancreatic lipomatosis, non-alcoholic fatty pancreatic disease,...
Fat infiltration in the pancreas is called pancreatic steatosis and it has several synonyms such as pancreatic lipomatosis, non-alcoholic fatty pancreatic disease, lipomatous pseudohypertrophy, fatty replacement, fatty pancreas and fatty infiltration. Pancreatic steatosis describes a disease ranging from infiltration of fat in the pancreas to pancreatic inflammation, and development of pancreatic fibrosis. There are multiple aetiologies of this condition, such as metabolic syndrome, alcohol intake, viral infections, toxins, congenital syndromes, etc. Pancreatic steatosis is usually diagnosed by trans-abdominal ultrasound, computed tomography scan and magnetic resonance imaging. Fatty infiltration in pancreas may lead to pancreatitis, diabetes mellitus and may be a predisposing cause of pancreatic cancer. Now a day, pancreatic steatosis is a common incidental finding during abdominal ultrasonography for other reasons and is a new challenge in Gastroenterology. But there is no guideline for pancreatic steatosis till now. In this review article, we are trying to give an overall idea (aetiologies, diagnosis, management, clinical significances) on pancreatic steatosis.
Topics: Fatty Liver; Gastroenterology; Humans; Metabolic Syndrome; Pancreas; Pancreatic Diseases
PubMed: 32490903
DOI: 10.1590/s0004-2803.202000000-27 -
Langenbeck's Archives of Surgery May 2021Acute pancreatitis (AP) is defined as an acute inflammatory attack of the pancreas of sudden onset. Around 25% of patients have either moderately severe or severe... (Review)
Review
BACKGROUND
Acute pancreatitis (AP) is defined as an acute inflammatory attack of the pancreas of sudden onset. Around 25% of patients have either moderately severe or severe disease with a mortality rate of 15-20%.
PURPOSE
The aim of this article was to summarize the advances being made in the understanding of this disease and the important role of surgery.
RESULTS AND CONCLUSIONS
An accurate diagnosis should be made a soon as possible, initiating resuscitation with large volume intravenous fluids and oxygen by mask. Predicted severe disease will require intensive monitoring. Most deaths within the first week are due to multi-organ failure; thus, these patients will require intensive therapy unit management. During the second phase of the disease, death is due to local complications arising from the pancreatic inflammation, requiring accurate identification to determine the correct form of treatment. Acute peripancreatic fluid collections arise < 4 weeks after onset of interstitial edematous pancreatitis, not requiring any treatment. Most pancreatic pseudocysts arise > 4 weeks and largely resolve on conservative management. Necrotizing pancreatitis causing acute necrotic collections and later walled-off necrosis will require treatment if symptomatic or infected. Initial endoscopic transgastric or percutaneous drainage will resolve less serious collections but necrosectomy using minimally invasive approaches will be needed for more serious collections. To prevent recurrent attacks of AP, causative factors need to be removed where possible such as cholecystectomy and cessation of alcohol. Future progress requires improved management of multi-organ failure and more effective minimally invasive techniques for the removal of necrosis.
Topics: Acute Disease; Drainage; Humans; Pancreas; Pancreatitis, Acute Necrotizing
PubMed: 32910276
DOI: 10.1007/s00423-020-01944-6 -
Molecules (Basel, Switzerland) Dec 2022The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes.... (Review)
Review
The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes. Pancreatitis is characterized by inflammation of the pancreas leading to temporary or permanent pancreatic dysfunction. Inflammation and fibrosis caused by chronic pancreatitis exacerbate malignant transformation and significantly increase the risk of developing pancreatic cancer, the world's most aggressive cancer with a 5-year survival rate less than 10%. Berberine (BBR) is a naturally occurring plant-derived polyphenol present in a variety of herbal remedies used in traditional medicine to treat ulcers, infections, jaundice, and inflammation. The current review summarizes the existing in vitro and in vivo evidence on the effects of BBR against pancreatitis and pancreatic cancer with a focus on the signalling mechanisms underlying the effects of BBR.
Topics: Humans; Berberine; Pancreatitis; Pancreas; Pancreatic Neoplasms; Inflammation
PubMed: 36500723
DOI: 10.3390/molecules27238630 -
Gastroenterology Jan 2015We previously established long-term, 3-dimensional culture of organoids from mouse tissues (intestine, stomach, pancreas, and liver) and human intestine and pancreas....
BACKGROUND & AIMS
We previously established long-term, 3-dimensional culture of organoids from mouse tissues (intestine, stomach, pancreas, and liver) and human intestine and pancreas. Here we describe conditions required for long-term 3-dimensional culture of human gastric stem cells. The technology can be applied to study the epithelial response to infection with Helicobacter pylori.
METHODS
We generated organoids from surgical samples of human gastric corpus. Culture conditions were developed based on those for the mouse gastric and human intestinal systems. We used microinjection to infect the organoids with H pylori. Epithelial responses were measured using microarray and quantitative polymerase chain reaction analyses.
RESULTS
Human gastric cells were expanded indefinitely in 3-dimensional cultures. We cultured cells from healthy gastric tissues, single-sorted stem cells, or tumor tissues. Organoids maintained many characteristics of their respective tissues based on their histology, expression of markers, and euploidy. Organoids from healthy tissue expressed markers of 4 lineages of the stomach and self-organized into gland and pit domains. They could be directed to specifically express either lineages of the gastric gland, or the gastric pit, by addition of nicotinamide and withdrawal of WNT. Although gastric pit lineages had only marginal reactions to bacterial infection, gastric gland lineages mounted a strong inflammatory response.
CONCLUSIONS
We developed a system to culture human gastric organoids. This system can be used to study H pylori infection and other gastric pathologies.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cell Culture Techniques; Cell Lineage; Cell Proliferation; Cell Separation; Cells, Cultured; Epithelial Cells; Female; Gastric Mucosa; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Niacinamide; Organoids; Phenotype; Ploidies; Stem Cells; Stomach; Time Factors; Wnt Proteins
PubMed: 25307862
DOI: 10.1053/j.gastro.2014.09.042 -
Nutrients Apr 2023The nutritional management of acute pancreatitis (AP) patients has widely changed over time. The "pancreatic rest" was the cornerstone of the old paradigm, and... (Review)
Review
The nutritional management of acute pancreatitis (AP) patients has widely changed over time. The "pancreatic rest" was the cornerstone of the old paradigm, and nutritional support was not even included in AP management. Traditional management of AP was based on intestinal rest, with or without complete parenteral feeding. Recently, evidence-based data underlined the superiority of early oral or enteral feeding with significantly decreased multiple-organ failure, systemic infections, surgery need, and mortality rate. Despite the current recommendations, experts still debate the best route for enteral nutritional support and the best enteral formula. The aim of this work is to collect and analyze evidence over the nutritional aspects of AP management to investigate its impact. Moreover, the role of immunonutrition and probiotics in modulating inflammatory response and gut dysbiosis during AP was extensively studied. However, we have no significant data for their use in clinical practice. This is the first work to move beyond the mere opposition between the old and the new paradigm, including an analysis of several topics still under debate in order to provide a comprehensive overview of nutritional management of AP.
Topics: Humans; Pancreatitis; Acute Disease; Enteral Nutrition; Pancreas; Nutritional Support
PubMed: 37111158
DOI: 10.3390/nu15081939 -
Endocrine Reviews Jul 2023The evidence for an association between coxsackievirus B (CVB) infection, pancreatic islet autoimmunity, and clinical type 1 diabetes is increasing. Results from...
The evidence for an association between coxsackievirus B (CVB) infection, pancreatic islet autoimmunity, and clinical type 1 diabetes is increasing. Results from prospective cohorts and pancreas histopathology studies have provided a compelling case. However, the demonstration of a causal relationship is missing, and is likely to remain elusive until tested in humans by avoiding exposure to this candidate viral trigger. To this end, CVB vaccines have been developed and are entering clinical trials. However, the progress made in understanding the biology of the virus and in providing tools to address the long-standing question of causality contrasts with the scarcity of information about the antiviral immune responses triggered by infection. Beta-cell death may be primarily induced by CVB itself, possibly in the context of poor immune protection, or secondarily provoked by T-cell responses against CVB-infected beta cells. The possible involvement of epitope mimicry mechanisms skewing the physiological antiviral response toward autoimmunity has also been suggested. We here review the available evidence for each of these 3 non-mutually exclusive scenarios. Understanding which ones are at play is critical to maximize the odds of success of CVB vaccination, and to develop suitable tools to monitor the efficacy of immunization and its intermingling with autoimmune onset or prevention.
Topics: Humans; Diabetes Mellitus, Type 1; Prospective Studies; Enterovirus B, Human; Coxsackievirus Infections; Insulin-Secreting Cells
PubMed: 36884282
DOI: 10.1210/endrev/bnad007 -
BMJ Case Reports Jul 2019A 22-year-old female patient was admitted to hospital after being referred from the oral medicine clinic where she had been seen for persistent gingivitis and mouth...
A 22-year-old female patient was admitted to hospital after being referred from the oral medicine clinic where she had been seen for persistent gingivitis and mouth ulcers. She described an insidious history of persistent fevers, dry cough and unexplained weight loss over 4-6 weeks. Imaging showed extensive bilateral pulmonary nodules with mediastinal lymphadenopathy and two lesions in the pancreas. MRI revealed these lesions to be well-defined fluid-filled cysts in the tail of the pancreas, without features of malignancy. Core biopsies taken from her lung nodules demonstrated features of vasculitis with granulomata. This was consistent with her positive immunology for c-antinuclear cytoplasmic antibodies and proteinase-3, which were sent after her fever failed to settle with antibiotic treatment. In keeping with a diagnosis of vasculitis, the patient showed a significant clinical and biochemical response to intravenous methylprednisolone and high-dose daily prednisolone thereafter.
Topics: Administration, Intravenous; Antibodies, Antineutrophil Cytoplasmic; Diagnosis, Differential; Female; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Lung; Lymphadenopathy; Mediastinal Neoplasms; Methylprednisolone; Myeloblastin; Pancreas; Treatment Outcome; Young Adult
PubMed: 31289155
DOI: 10.1136/bcr-2018-228693 -
Cell Stem Cell Jul 2020SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19...
SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.
Topics: Angiotensin-Converting Enzyme 2; Animals; Autopsy; Betacoronavirus; COVID-19; Cell Line; Coronavirus Infections; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Liver; Mice; Models, Biological; Organoids; Pancreas; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Tropism; Virus Internalization
PubMed: 32579880
DOI: 10.1016/j.stem.2020.06.015 -
Gastroenterology Dec 2021Acute pancreatitis (AP) is an inflammatory disease with mild to severe course that is associated with local and systemic complications and significant mortality.... (Comparative Study)
Comparative Study
BACKGROUND AND AIMS
Acute pancreatitis (AP) is an inflammatory disease with mild to severe course that is associated with local and systemic complications and significant mortality. Uncovering inflammatory pathways that lead to progression and recovery will inform ways to monitor and/or develop effective therapies.
METHODS
We performed single-cell mass Cytometry by Time Of Flight (CyTOF) analysis to identify pancreatic and systemic inflammatory signals during mild AP (referred to as AP), severe AP (SAP), and recovery using 2 independent experimental models and blood from patients with AP and recurrent AP. Flow cytometric validation of monocytes subsets identified using CyTOF analysis was performed independently.
RESULTS
Ly6C inflammatory monocytes were the most altered cells in the pancreas during experimental AP, recovery, and SAP. Deep profiling uncovered heterogeneity among pancreatic and blood monocytes and identified 7 novel subsets during AP and recovery, and 6 monocyte subsets during SAP. Notably, a dynamic shift in pancreatic CD206 macrophage population was observed during AP and recovery. Deeper profiling of the CD206 macrophage identified 7 novel subsets during AP, recovery, and SAP. Differential expression analysis of these novel monocyte and CD206 macrophage subsets revealed significantly altered surface (CD44, CD54, CD115, CD140a, CD196, podoplanin) and functional markers (interferon-γ, interleukin 4, interleukin 22, latency associated peptide-transforming growth factor-β, tumor necrosis factor-α, T-bet, RoRγt) that were associated with recovery and SAP. Moreover, a targeted functional analysis further revealed distinct expression of pro- and anti-inflammatory cytokines by pancreatic CD206 macrophage subsets as the disease either progressed or resolved. Similarly, we identified heterogeneity among circulating classical inflammatory monocytes (CD14CD16) and novel subsets in patients with AP and recurrent AP.
CONCLUSIONS
We identified several novel monocyte/macrophage subsets with unique phenotype and functional characteristics that are associated with AP, recovery, and SAP. Our findings highlight differential innate immune responses during AP progression and recovery that can be leveraged for future disease monitoring and targeting.
Topics: Animals; Biomarkers; Cell Separation; Disease Models, Animal; Female; Flow Cytometry; Humans; Immunity, Innate; Immunophenotyping; Macrophages; Mice, Inbred BALB C; Monocytes; Pancreas; Pancreatitis; Phenotype; Recovery of Function; Severity of Illness Index; Time Factors; Mice
PubMed: 34450180
DOI: 10.1053/j.gastro.2021.08.033