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Stem Cell Reviews and Reports Feb 2020Existence of stem cells in adult pancreas remains contentious. Single cells suspensions obtained by collagenase and trypsin digestion separately from adult mouse...
Existence of stem cells in adult pancreas remains contentious. Single cells suspensions obtained by collagenase and trypsin digestion separately from adult mouse pancreas and pancreatic islets were spun at 1000 rpm (250 g) to collect the cells. At this speed the stem/ progenitor cells remained buoyant and were further enriched by spinning the supernatant at 3000 rpm (1000 g). Two distinct populations of stem cells were detected including pluripotent, very small (2-6 μm) embryonic-like stem cells (VSELs) that expressed nuclear OCT-4A and pluripotent transcripts (Oct-4A, Sox2, Nanog, Stella) and slightly bigger progenitors, pancreatic stem cells (PSCs) that expressed cytoplasmic OCT-4B and PDX-1. Streptozotocin treated diabetic pancreas showed an increase in numbers of VSELs (2-6 μm, 7AAD-, LIN-CD45-SCA1+ cells) and up-regulation of transcripts specific for stem/ progenitor cells. Diabetic mice were further subjected to partial pancreatectomy to study involvement of VSELs/ PSCs during regeneration. VSELs/ PSCs were mobilized in large numbers, were observed in the lumen of blood vessels and PCNA expression suggested their proliferation. Initially, new acini assembled to regenerate the exocrine pancreas and later by Day 30, neogenesis of islets was observed in the vicinity of the blood vessels and pancreatic ducts by the differentiation of endogenous VSELs/ PSCs which may be targeted to regenerate diabetic pancreas in clinical settings.
Topics: Animals; Cell Differentiation; Diabetes Mellitus, Experimental; Embryonic Stem Cells; Humans; Islets of Langerhans; Mice; Pancreas; Pancreatectomy; Pluripotent Stem Cells; Regeneration; Stem Cell Transplantation; Stem Cells
PubMed: 31705263
DOI: 10.1007/s12015-019-09919-x -
Function (Oxford, England) 2023George Palade's pioneering electron microscopical studies of the pancreatic acinar cell revealed the intracellular secretory pathway from the rough endoplasmic reticulum... (Review)
Review
George Palade's pioneering electron microscopical studies of the pancreatic acinar cell revealed the intracellular secretory pathway from the rough endoplasmic reticulum at the base of the cell to the zymogen granules in the apical region. Palade also described for the first time the final stage of exocytotic enzyme secretion into the acinar lumen. The contemporary studies of the mechanism by which secretion is acutely controlled, and how the pancreas is destroyed in the disease acute pancreatitis, rely on monitoring molecular events in the various identified pancreatic cell types in the living pancreas. These studies have been carried out with the help of high-resolution fluorescence recordings, often in conjunction with patch clamp current measurements. In such studies we have gained much detailed information about the regulatory events in the exocrine pancreas in health as well as disease, and new therapeutic opportunities have been revealed.
Topics: Humans; Pancreas, Exocrine; Pancreatitis; Acute Disease; Pancreas; Acinar Cells
PubMed: 36606242
DOI: 10.1093/function/zqac061 -
Journal of Gastroenterology and... Aug 2023Over last few years, there has been a paradigm shift in the management of infected pancreatic necrosis with endoscopic and minimally invasive "step-up" management... (Review)
Review
Over last few years, there has been a paradigm shift in the management of infected pancreatic necrosis with endoscopic and minimally invasive "step-up" management approach replacing open surgical necrosectomy. Because of being associated with reduced occurrence of new onset multi-organ failure, external pancreatic fistulae, shorter hospital stay, lower costs, and better quality of life compared with minimally invasive surgical approach, endoscopic "step-up" management approach is the preferred intervention for endoscopically accessible pancreatic necrotic collections at expert centers with endoscopic expertise. Development of lumen apposing metal stents and improvised accessories for interventional endoscopic ultrasound has revolutionized the endoscopic management of pancreatic necrosis making it more effective and safer. Despite these promising developments, endoscopic transluminal necrosectomy (ETN) remains the Achilles heel. Lack of dedicated endoscopic accessories, poor endoscopic visualization within the necrotic cavity, limited diameter of the instrument channel of the endoscope that is a significant impediment to remove large amount of necrotic material, and uncertain ability to avoid vessels and vital structures in the necrotic cavity are important limitations during endoscopic necrosectomy. Recent devices and solutions including use of cap assisted necrosectomy, over the scope grasper and powered endoscopic debridement device are welcome steps in our pursuit for an ideal, safer, and efficacious ETN device. This review will discuss recent advances as well as challenges in the endoscopic management of pancreatic necrosis.
Topics: Humans; Pancreatitis, Acute Necrotizing; Quality of Life; Endoscopy; Pancreas; Stents; Drainage; Necrosis; Treatment Outcome
PubMed: 37309053
DOI: 10.1111/jgh.16262 -
Cell Stem Cell Jun 2021In this issue of Cell Stem Cell, Huang et al. (2021) and Breunig et al. (2021) developed human stem-cell-derived organoid culture systems to recapitulate pancreatic...
In this issue of Cell Stem Cell, Huang et al. (2021) and Breunig et al. (2021) developed human stem-cell-derived organoid culture systems to recapitulate pancreatic acinar and ductal lineages. This provides opportunities to study cellular plasticity and transformation in pancreatic cancer initiation and progression.
Topics: Acinar Cells; Humans; Organoids; Pancreas; Pancreas, Exocrine; Pancreatic Ducts; Pancreatic Neoplasms; Pluripotent Stem Cells
PubMed: 34087158
DOI: 10.1016/j.stem.2021.05.006 -
Clinical Transplantation Aug 2020Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP-IAT). We assessed if pancreas volume...
Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP-IAT). We assessed if pancreas volume calculated with preoperative MRI could assess islet yield and postoperative outcomes. We reviewed dynamic MRI studies from 154 adult TP-IAT patients (2009-2016), and associations between calculated volumes and digest islet equivalents (IEQs) were tested. In multivariate regression analysis, pancreas volume (P < .001) and preoperative HbA1c levels (P = .009) were independently associated with digest IEQs. The IEQ prediction formula was calculated according to each preoperative HbA1c level, (a) pancreas volume × 5800 for HbA1c ≥ 6.5, (b) pancreas volume × 10 000 for HbA1c ≥5.7/<6.5 and (iii) pancreas volume × 11 400 for HbA1c < 5.7. The formula was internally validated with 28 TP-IAT patients between 2017 and 2018 (r = .657 and r = .710 when restricted to 24 patients without prior pancreatectomy). An estimated IEQs/Body Weight (kg) ≥3700 predicted HbA1c ≤6.5 and insulin independence at 1 year after TP-IAT with 77% and 88% sensitivity and 55% and 43% specificity, respectively. The combination of pancreas volume and preoperative HbA1c levels may be useful to estimate islet yield. Estimated IEQs were reasonably sensitive to predict acceptable glucose control at 1 year.
Topics: Adult; Glycated Hemoglobin; Humans; Islets of Langerhans Transplantation; Pancreas; Pancreatectomy; Pancreatitis, Chronic; Transplantation, Autologous; Treatment Outcome
PubMed: 32530540
DOI: 10.1111/ctr.14008 -
Relationship Between Remnant Pancreatic Volume and Endocrine Function After Pancreaticoduodenectomy.The American Surgeon Feb 2022Decreased pancreatic volume (PV) is a predictive factor for diabetes mellitus (DM) after surgery. There are few reports on PV and endocrine function pre- and...
BACKGROUND
Decreased pancreatic volume (PV) is a predictive factor for diabetes mellitus (DM) after surgery. There are few reports on PV and endocrine function pre- and post-surgery. We investigated the correlation between PV and insulin secretion.
METHODS
Seventeen patients underwent pancreaticoduodenectomy (PD) Pre- and post-surgery PV and C-peptide index (CPI) measurements were performed. Additionally, the correlation between PV and CPI was analyzed.
RESULTS
The mean preoperative PV (PPV) was 55.1 ± 31.6 mL, postoperative remnant PV (RPV) was 25.3±17.3 mL, and PV reduction was 53%. The mean preoperative C-peptide immunoreactivity (CPR) was 1.39 ± .51 and postoperative CPR was .85±.51. The mean preoperative CPI was 1.29±.72 and postoperative CPI was .73 ± .48. Significant correlations were observed between RPV and post CPR (ρ = .507, P = .03) and post CPI (ρ = .619, P = .008).
DISCUSSION
There was a significant correlation between RPV and CPI after PD. A smaller RPV resulted in lower insulin secretion ability, increasing the potential risk of new-onset DM after PD.
Topics: Aged; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Male; Multidetector Computed Tomography; Organ Size; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Period; Preoperative Period; Retrospective Studies
PubMed: 33522272
DOI: 10.1177/0003134821989049 -
Archivum Immunologiae Et Therapiae... Apr 2020Interactions between the immune system and the pancreas are pivotal in understanding how and why β cells' damage causes problems with pancreas functioning. Pancreatic... (Review)
Review
Crosstalk Between Immunity System Cells and Pancreas. Transformation of Stem Cells Used in the 3D Bioprinting Process as a Personalized Treatment Method for Type 1 Diabetes.
Interactions between the immune system and the pancreas are pivotal in understanding how and why β cells' damage causes problems with pancreas functioning. Pancreatic islets are crucial in maintaining glucose homeostasis in organs, tissue and cells. Autoimmune aggression towards pancreatic islets, mainly β cells, leads to type 1 diabetes-one of the most prevalent autoimmune disease in the world, being a worldwide risk to health of many people. In this review, we highlight the role of immune cells and its influence in the development of autoimmunity in Langerhans islets. Moreover, we discuss the impact of the immunological factors on future understanding possible recurrence of autoimmunity on 3D-bioprinted bionic pancreas.
Topics: Autoimmunity; Bioprinting; Diabetes Mellitus, Type 1; Humans; Immune System; Insulin-Secreting Cells; Islets of Langerhans; Islets of Langerhans Transplantation; Pancreas; Stem Cells
PubMed: 32297019
DOI: 10.1007/s00005-020-00578-2 -
Current Issues in Molecular Biology May 2021Chronic adrenergic stimulation is the dominant factor in impairment of the β-cell function. Sustained adrenergic exposure generates dysregulated insulin secretion in...
Chronic adrenergic stimulation is the dominant factor in impairment of the β-cell function. Sustained adrenergic exposure generates dysregulated insulin secretion in fetal sheep. Similar results have been shown in Min6 under the elevated epinephrine condition, but impairments after adrenergic removal are still unknown and a high rate of proliferation in Min6 has been ignored. Therefore, we incubated primary rats' islets with half maximal inhibitory concentrations of epinephrine for three days, then determined their insulin secretion responsiveness and related signals two days after removal of adrenaline via radioimmunoassay and qPCR. Insulin secretion was not different between the exposure group (1.07 ± 0.04 ng/islet/h) and control (1.23 ± 0.17 ng/islet/h), but total islet insulin content after treatment (5.46 ± 0.87 ng/islet/h) was higher than control (3.17 ± 0.22 ng/islet/h, < 0.05), and the fractional insulin release was 36% ( < 0.05) lower after the treatment. Meanwhile, the mRNA expression of Gαs, Gαz and Gβ1-2 decreased by 42.8% 19.4% and 24.8%, respectively ( < 0.05). Uncoupling protein 2 (Ucp2), sulphonylurea receptor 1 (Sur1) and superoxide dismutase 2 (Sod2) were significantly reduced (38.5%, 23.8% and 53.8%, < 0.05). Chronic adrenergic exposure could impair insulin responsiveness in primary pancreatic islets. Decreased G proteins and Sur1 expression affect the regulation of insulin secretion. In conclusion, the sustained under-expression of Ucp2 and Sod2 may further change the function of β-cell, which helps to understand the long-term adrenergic adaptation of pancreatic β-cell.
Topics: Adaptation, Physiological; Adrenergic beta-Agonists; Animals; Epinephrine; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreas; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Uncoupling Protein 2
PubMed: 34071501
DOI: 10.3390/cimb43010020 -
Journal of Hepato-biliary-pancreatic... Feb 2022Factors aggravating remnant pancreas atrophy following pancreatoduodenectomy and the effects of atrophy have not been extensively studied. This study aimed to evaluate...
BACKGROUND
Factors aggravating remnant pancreas atrophy following pancreatoduodenectomy and the effects of atrophy have not been extensively studied. This study aimed to evaluate the clinical factors affecting remnant pancreas atrophy and assess the effects of atrophy on quality of life, nutritional status, and pancreatic exocrine and endocrine functions.
METHODS
Data collected prospectively from 122 patients who completed 12 months of follow-up, including computed tomography and the quality-of-life questionnaire, were analyzed. Pancreas volume was measured using a computed tomography volumetry program. Endocrine and exocrine functions were evaluated.
RESULTS
Malignancy and adjuvant chemoradiotherapy were associated with severity of atrophy. At 12 postoperative months, quality-of-life scores and nutritional indexes were mostly not associated with atrophy, but stool elastase level decreased significantly and incidence of new-onset diabetes mellitus was higher in the severe atrophy group. Postprandial 2-hour blood glucose and glycosylated hemoglobin levels were also higher in this group.
CONCLUSIONS
Remnant pancreas atrophy was more severe in patients with malignant disease who received adjuvant chemoradiotherapy and was associated with pancreatic exocrine and endocrine functions. More careful monitoring and active management of exocrine and endocrine deficiencies are necessary for patients who underwent pancreatoduodenectomy for malignant disease and received chemoradiotherapy.
Topics: Atrophy; Humans; Nutritional Status; Pancreas; Pancreaticoduodenectomy; Quality of Life; Risk Factors
PubMed: 33773065
DOI: 10.1002/jhbp.949 -
Chirurgie (Heidelberg, Germany) Aug 2023Pancreatic injuries resulting from blunt abdominal trauma are uncommon but carry a high risk of morbidity and mortality for patients. Prompt diagnosis and management... (Review)
Review
Pancreatic injuries resulting from blunt abdominal trauma are uncommon but carry a high risk of morbidity and mortality for patients. Prompt diagnosis and management are critical to optimize patient outcomes. This review article provides an overview of the different types of pancreatic injuries and the various management strategies available, based on the severity of the injury. In unstable patients with a positive focused assessment with sonography for trauma (FAST), immediate trauma laparotomy is required. Stable patients should be assessed with contrast-enhanced computed tomography (CT) imaging. Low-grade injuries can be managed with irrigation and drainage. In cases of left-sided ductal injury below the level of the portal vein, left-sided pancreatic resection is often necessary. Higher grade injuries to the pancreatic head need to be evaluated in the context of other accompanying injuries, where damage control may be required. Pancreaticoduodenectomy is a rare intervention and is usually only required in the later course in these cases.
Topics: Humans; Pancreas; Pancreatectomy; Pancreaticoduodenectomy; Tomography, X-Ray Computed; Abdominal Injuries; Wounds, Nonpenetrating; Thoracic Injuries
PubMed: 37369739
DOI: 10.1007/s00104-023-01898-7