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Emerging Microbes & Infections Dec 2022Diabetes mellitus (DM) is one of the most common underlying diseases that may aggravates COVID-19. In the present study, we explored islet function, the presence of...
Diabetes mellitus (DM) is one of the most common underlying diseases that may aggravates COVID-19. In the present study, we explored islet function, the presence of SARS-CoV-2 and pathological changes in the pancreas of patients with COVID-19. Oral glucose tolerance tests (OGTTs) and the C-peptide release test demonstrated a decrease in glucose-stimulated C-peptide secretory capacity and an increase in HbA1c levels in patients with COVID-19. The prediabetic conditions appeared to be more significant in the severe group than in the moderate group. SARS-CoV-2 receptors (ACE2, CD147, TMPRSS2 and neuropilin-1) were expressed in pancreatic tissue. In addition to SARS-CoV-2 virus spike protein and virus RNA, coronavirus-like particles were present in the autophagolysosomes of pancreatic acinar cells of a patient with COVID-19. Furthermore, the expression and distribution of various proteins in pancreatic islets of patients with COVID-19 were altered. These data suggest that SARS-CoV-2 in the pancreas may directly or indirectly impair islet function.
Topics: C-Peptide; COVID-19; Diabetes Mellitus; Humans; Pancreas; SARS-CoV-2
PubMed: 35343389
DOI: 10.1080/22221751.2022.2059400 -
Journal of Diabetes Investigation Dec 2021Two recent reports denoted the potential of SARS-CoV-2 to directly infect β-cells and the possible fate of β-cells under COVID-19. The fight against SARS-CoV-2 will... (Review)
Review
Two recent reports denoted the potential of SARS-CoV-2 to directly infect β-cells and the possible fate of β-cells under COVID-19. The fight against SARS-CoV-2 will continue to develop more effective therapeutic strategies for diabetes.
Topics: COVID-19; Diabetes Mellitus; Humans; Insulin-Secreting Cells; SARS-CoV-2
PubMed: 34529355
DOI: 10.1111/jdi.13671 -
Revista Espanola de Enfermedades... Sep 2021A 41-year-old caucasian female, with past medical history of pituitary adenoma medicated with cabergoline, presented with worsening dyspepsia and unintentional weight...
A 41-year-old caucasian female, with past medical history of pituitary adenoma medicated with cabergoline, presented with worsening dyspepsia and unintentional weight loss of 5%. Physical exam and laboratory results were unremarkable for pathological findings. Esophagogastroduodenoscopy revealed an oedematous and exuberant lymphangiectasia appearance in the duodenum, with no ulceration or suspected infiltration component. However, duodenal biopsies revealed infiltration by poorly differentiated carcinoma. In the meantime, infection and inflammatory/autoimmune causes were ruled out. A CT scan was performed revealing a thickened and enlarged pancreas with ill-defined limits and several intra-abdominal adenopathies, raising suspicion of pancreatic lymphoproliferative disease. EUS with FNB was performed with biopsy of the pancreas and one of the larger adenopathy. EUS also revealed an enlarged, non-nodular pancreas and a thickened duodenal wall. Mild ascites was detected. Both EUS-biopsies were concordant on the diagnosis of carcinoma with gastric or pancreatic-biliary origin, highly aggressive (Ki67 > 80 %). Therefore, the diagnosis of pancreatic adenocarcinoma was assumed (cT4N1Mx). The patient is currently on palliative chemotherapy and remains paucisymptomatic.
Topics: Adenocarcinoma; Adult; Duodenum; Female; Humans; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms
PubMed: 33569966
DOI: 10.17235/reed.2021.7823/2021 -
Physiological Reports Apr 2022Viral infections are linked to the progression of inflammatory reactions and oxidative stress that play pivotal roles in systemic diseases. To confirm this phenomenon,...
Viral infections are linked to the progression of inflammatory reactions and oxidative stress that play pivotal roles in systemic diseases. To confirm this phenomenon, in the present study, TNF-α level and oxidative stress markers were examined in the liver, kidney, and pancreas of HTLV1-infected male BALB/c mice. To this end, twenty BALB/c mice were divided into HTLV1-infected mice that were inoculated with 1-million HTLV1-infected cells (MT-2), and the control groups. Two months after inoculation, the peripheral blood, mesenteric lymph nodes, liver, kidney, and pancreas were collected after deep anesthetization of mice (ketamine, 30 mg/kg). The extracted DNA of mesenteric lymph nodes was obtained to quantify proviral load (PVL) using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of lipid peroxidation, total thiol (SH), nitric oxide (NO), TNF-α, catalase (CAT), and superoxide dismutase (SOD) activities were examined in the liver, kidney, and pancreases. Furthermore, histopathological changes in the liver and kidney were evaluated. In liver tissue, the levels of MDA, TNF-α, and blood cell infiltration were significantly increased, and the levels of CAT and SOD were significantly decreased. In the kidney, a reduction in SOD, CAT, and total SH and an increase in MDA and NO were observed. In the pancreas, CAT activity, total SH, and SOD were decreased, and the levels of MDA and NO were enhanced. In terms of TNF-α production, it has been shown that the level of this inflammatory cytokine was increased in the liver, kidney, and pancreas. The HTLV1 may have a role in inducing inflammatory reactions and oxidative stress pathways in the tissues.
Topics: Animals; Kidney; Liver; Male; Mice; Mice, Inbred BALB C; Oxidative Stress; Pancreas; Pancrelipase; Superoxide Dismutase
PubMed: 35373925
DOI: 10.14814/phy2.15243 -
Parasitology Research Mar 2017The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of... (Review)
Review
The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of immigration, this disease has now been diagnosed in non-endemic areas worldwide. Although, the heart and gastrointestinal tract are the most studied, the insulin-secreting β cell of the endocrine pancreas is also a target of infection. In this review, we summarize available clinical and laboratory evidence to determine whether T. cruzi-infection-mediated changes of β cell function is likely to contribute to the development of hyperglycemia and diabetes. Our literature survey indicates that T. cruzi infection of humans and of experimental animals relates to altered secretory behavior of β cells. The mechanistic basis of these observations appears to be a change in stimulus-secretion pathway function rather than the loss of insulin-producing β cells. Whether this attenuated insulin release ultimately contributes to the pathogenesis of diabetes in human Chagas disease, however, remains to be determined. Since the etiologies of diabetes are multifactorial including genetic and lifestyle factors, the use of cell- and animal-based investigations, allowing direct manipulation of these factors, are important tools in testing if reduced insulin secretion has a causal influence on diabetes in the setting of Chagas disease. Long-term clinical investigations will be required to investigate this link in humans.
Topics: Animals; Chagas Disease; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Pancreas; Trypanosoma cruzi
PubMed: 28013375
DOI: 10.1007/s00436-016-5350-5 -
Revista Do Colegio Brasileiro de... 2023The first cases of the COVID-19 disease were identified in late 2019 in China, but it didnt take long for it to become pandemic. At first, it was believed that it was... (Review)
Review
The first cases of the COVID-19 disease were identified in late 2019 in China, but it didnt take long for it to become pandemic. At first, it was believed that it was restricted to respiratory symptoms only, until extrapulmonary manifestations were reported worldwide. Acute pancreatitis concomitant with the diagnosis of SARS-CoV-2 infection has been observed in some patients, in the absence of the most common etiologies described in the literature. It is postulated that the presence of the ECA-2 viral receptor in the pancreas is responsible for the direct cellular damage and that the hyperinflammatory state of COVID-19 favors the development of pancreatitis through an immune-mediated mechanism. This study aimed to analyze the correlation between acute pancreatitis and COVID-19 disease as a probable causality factor. An integrative literature review was carried out, including studies published between January 2020 and December 2022 that brought data on patients diagnosed with acute pancreatitis according to the revised Atlanta Classification with a confirmed diagnosis of COVID-19 in the same period. A total of thirty studies were reviewed. Demographic, clinical, laboratory and imaging aspects were analyzed and discussed. It is believed that SARS-CoV-2 was responsible for the development of acute pancreatitis in these patients, due to the absence of other precipitating risk factors, as well as the close temporal relationship between both. Attention should be given to gastrointestinal manifestations in patients affected by COVID-19.
Topics: Humans; COVID-19; Pancreatitis; SARS-CoV-2; Acute Disease; Pancreas
PubMed: 37436286
DOI: 10.1590/0100-6991e-20233559-en -
Endoscopy Jun 2022A validated classification of endoscopic ultrasound (EUS) morphological characteristics and consequent therapeutic intervention(s) in pancreatic and peripancreatic fluid...
BACKGROUND
A validated classification of endoscopic ultrasound (EUS) morphological characteristics and consequent therapeutic intervention(s) in pancreatic and peripancreatic fluid collections (PFCs) is lacking. We performed an interobserver agreement study among expert endosonographers assessing EUS-related PFC features and the therapeutic approaches used.
METHODS
50 EUS videos of PFCs were independently reviewed by 12 experts and evaluated for PFC type, percentage solid component, presence of infection, recognition of and communication with the main pancreatic duct (MPD), stent choice for drainage, and direct endoscopic necrosectomy (DEN) performance and timing. The Gwet's AC1 coefficient was used to assess interobserver agreement.
RESULTS
A moderate agreement was found for lesion type (AC1, 0.59), presence of infection (AC1, 0.41), and need for DEN (AC1, 0.50), while fair or poor agreements were stated for percentage solid component (AC1, 0.15) and MPD recognition (AC1, 0.31). Substantial agreement was rated for ability to assess PFC-MPD communication (AC1, 0.69), decision between placing a plastic versus lumen-apposing metal stent (AC1, 0.62), and timing of DEN (AC1, 0.75).
CONCLUSIONS
Interobserver agreement between expert endosonographers regarding morphological features of PFCs appeared suboptimal, while decisions on therapeutic approaches seemed more homogeneous. Studies to achieve standardization of the diagnostic endosonographic criteria and therapeutic approaches to PFCs are warranted.
Topics: Drainage; Endosonography; Humans; Observer Variation; Pancreas; Pancreatic Diseases
PubMed: 34496421
DOI: 10.1055/a-1640-4365 -
Canadian Journal of Diabetes Mar 2023Navigating the coronavirus disease-2019 (COVID-19, now COVID) pandemic has required resilience and creativity worldwide. Despite early challenges to productivity, more... (Review)
Review
Navigating the coronavirus disease-2019 (COVID-19, now COVID) pandemic has required resilience and creativity worldwide. Despite early challenges to productivity, more than 2,000 peer-reviewed articles on islet biology were published in 2021. Herein, we highlight noteworthy advances in islet research between January 2021 and April 2022, focussing on 5 areas. First, we discuss new insights into the role of glucokinase, mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase and mitochondrial function on insulin secretion from the pancreatic β cell, provided by new genetically modified mouse models and live imaging. We then discuss a new connection between lipid handling and improved insulin secretion in the context of glucotoxicity, focussing on fatty acid-binding protein 4 and fetuin-A. Advances in high-throughput "omic" analysis evolved to where one can generate more finely tuned genetic and molecular profiles within broad classifications of type 1 diabetes and type 2 diabetes. Next, we highlight breakthroughs in diabetes treatment using stem cell-derived β cells and innovative strategies to improve islet survival posttransplantation. Last, we update our understanding of the impact of severe acute respiratory syndrome-coronavirus-2 infection on pancreatic islet function and discuss current evidence regarding proposed links between COVID and new-onset diabetes. We address these breakthroughs in 2 settings: one for a scientific audience and the other for the public, particularly those living with or affected by diabetes. Bridging biomedical research in diabetes to the community living with or affected by diabetes, our partners living with type 1 diabetes or type 2 diabetes also provide their perspectives on these latest advances in islet biology.
Topics: Animals; Mice; Biology; COVID-19; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Humans
PubMed: 36481263
DOI: 10.1016/j.jcjd.2022.11.003 -
Diabetologia May 2019In type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for... (Review)
Review
In type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for environmental factors has been postulated. Viral infections have long been considered as candidates for environmental triggers but, given the lack of evidence for an acute, widespread, cytopathic effect in the pancreas in type 1 diabetes or for a closely related temporal association of diabetes onset with such infections, a role for viruses in type 1 diabetes remains unproven. Moreover, viruses have rarely been isolated from the pancreas of individuals with type 1 diabetes, mainly (but not solely) due to the inaccessibility of the organ. Here, we review past and recent literature to evaluate the proposals that chronic, recurrent and, possibly, persistent enteroviral infections occur in pancreatic beta cells in type 1 diabetes. We also explore whether these infections may be sustained by different virus strains over time and whether multiple viral hits can occur during the natural history of type 1 diabetes. We emphasise that only a minority of beta cells appear to be infected at any given time and that enteroviruses may become replication defective, which could explain why they have been isolated from the pancreas only rarely. We argue that enteroviral infection of beta cells largely depends on the host innate and adaptive immune responses, including innate responses mounted by beta cells. Thus, we propose that viruses could play a role in type 1 diabetes on multiple levels, including in the triggering and chronic stimulation of autoimmunity and in the generation of inflammation and the promotion of beta cell dysfunction and stress, each of which might then contribute to autoimmunity, as part of a vicious circle. We conclude that studies into the effects of vaccinations and/or antiviral drugs (some of which are currently on-going) is the only means by which the role of viruses in type 1 diabetes can be finally proven or disproven.
Topics: Adaptive Immunity; Antiviral Agents; Autoimmunity; Biological Specimen Banks; Diabetes Mellitus, Type 1; Enterovirus Infections; Humans; Immunity, Innate; Insulin-Secreting Cells; Pancreas; Viral Vaccines
PubMed: 30675626
DOI: 10.1007/s00125-019-4811-7 -
Clinical Transplantation Nov 2022Complications leading to early technical failure have been the Achilles' heel of simultaneous pancreas-kidney transplantation (SPKT). The study purpose was to analyze...
BACKGROUND
Complications leading to early technical failure have been the Achilles' heel of simultaneous pancreas-kidney transplantation (SPKT). The study purpose was to analyze longitudinally our experience with early surgical complications following SPKT with an emphasis on changes in practice that improved outcomes in the most recent era.
STUDY DESIGN
Single center retrospective review of all SPKTs from 11/1/01 to 8/12/20 with enteric drainage. Early relaparotomy was defined as occurring within 3 months of SPKT. Patients were stratified into two sequential eras: Era 1 (E1): 11/1/01-5/30/13; Era 2 (E2) 6/1/13-8/12/20 based on changes in practice that occurred pursuant to donor age and pancreas cold ischemia time (CIT).
RESULTS
255 consecutive SPKTs were analyzed (E1, n = 165; E2, n = 90). E1 patients received organs from older donors (mean E1 27.3 vs. E2 23.1 years) with longer pancreas cold CITs) (mean E1 16.1 vs. E2 13.3 h, both p < .05). E1 patients had a higher early relaparotomy rate (E1 43.0% vs. E2 14.4%) and were more likely to require allograft pancreatectomy (E1 9.1% vs. E2 2.2%, both p < .05). E2 patients underwent systemic venous drainage more frequently (E1 8% vs. E2 29%) but pancreas venous drainage did not influence either relaparotomy or allograft pancreatectomy rates. The most common indications for early relaparotomy in E1 were allograft thrombosis (11.5%) and peri-pancreatic phlegmon/abscess (8.5%) whereas in E2 were thrombosis, pancreatitis/infection, and bowel obstruction (each 3%).
CONCLUSION
Maximizing donor quality (younger donors) and minimizing pancreas CIT are paramount for reducing early surgical complications following SPKT.
Topics: Humans; Pancreas Transplantation; Kidney Transplantation; Graft Survival; Postoperative Complications; Retrospective Studies; Treatment Outcome; Pancreas
PubMed: 36029250
DOI: 10.1111/ctr.14792