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Diabetes Sep 2020The human brain has inherent methodology to efficiently interpret complex environmental stimuli into understanding. This visual perception is governed by the law of...
The human brain has inherent methodology to efficiently interpret complex environmental stimuli into understanding. This visual perception is governed by the law of simplicity, which is fundamental to Gestalt theory. First introduced in a seminal article by Wertheimer in 1923, the theory explains how the mind groups similar images and fills in gaps in order to perceive an amenable version of reality. The world we see consists of complex visual scenes, but rarely is the entire picture visible to us. Since it is inefficient for all visual data to be analyzed at once, certain patterns are given higher importance and made to stand out from the rest of the field in our brain. Here we propose that Gestalt theory may explain why rodent islet architecture has historically been seen as having a core-mantle arrangement. By filling in apparent gaps in the non-β-cell lining, the mind interprets it as a "whole" mantle, which may have further led to widely accepted notions regarding islet microcirculation, intra-islet signaling, and islet development. They are largely based on the prevailing stereotypic islet architecture in which an enclosed structure is presumed. Three-dimensional analysis provides more integrated views of islet and pancreatic microcirculation.
Topics: Animals; Humans; Islets of Langerhans; Pancreas
PubMed: 32669392
DOI: 10.2337/db20-0304 -
Revista Espanola de Enfermedades... Aug 2016Agenesis of the dorsal pancreas is a rare malformation. Since 1911 and until 2008, 53 cases have been reported. Several authors have recently described the association... (Review)
Review
BACKGROUND
Agenesis of the dorsal pancreas is a rare malformation. Since 1911 and until 2008, 53 cases have been reported. Several authors have recently described the association of this anomaly with neoplasia of the ventral pancreas, thus we performed a systematic review of the literature from 2008 to 2015.
METHODS
A systematic review of the MedLine and ISI Web of Science Databases from 2008 until 2015 was carried out, and 30 articles which met the inclusion criteria were identified that included a total of 53 patients: 7 children and 46 adults.
CONCLUSIONS
Although dorsal pancreatic agenesis is a rare malformation, given its association with non-alcoholic pancreatitis and neoplasia of the residual pancreas, physicians should maintain an expectant attitude.
Topics: Adult; Child; Cholangiopancreatography, Endoscopic Retrograde; Congenital Abnormalities; Humans; Pancreas; Pancreatitis
PubMed: 27468966
DOI: 10.17235/reed.2016.4474/2016 -
International Journal of Molecular... Oct 2019Adenosine regulates exocrine and endocrine secretions in the pancreas. Adenosine is considered to play a role in acini-to-duct signaling in the exocrine pancreas. To...
Adenosine regulates exocrine and endocrine secretions in the pancreas. Adenosine is considered to play a role in acini-to-duct signaling in the exocrine pancreas. To identify the molecular basis of functional adenosine receptors in the exocrine pancreas, immunohistochemical analysis was performed in the rat, mouse, and guinea pig pancreas, and the secretory rate and concentration of HCO in pancreatic juice from the rat pancreas were measured. The A adenosine receptor colocalized with ezrin, an A-kinase anchoring protein, in the luminal membrane of duct cells in the mouse and guinea pig pancreas. However, a strong signal ascribed to A adenosine receptors was detected in insulin-positive β cells in islets of Langerhans. The A adenosine receptor agonist 4-[2-[[6-Amino-9-(-ethyl-β-D-ribofuranuronamidosyl)-9-purin-2-yl]amino]ethyl]benzenepropanoic acid (CGS 21680) stimulated HCO-rich fluid secretion from the rat pancreas. These results indicate that A adenosine receptors may be, at least in part, involved in the exocrine secretion of pancreatic duct cells via acini-to-duct signaling. The adenosine receptors may be a potential therapeutic target for cancer as well as exocrine dysfunctions of the pancreas.
Topics: Animals; Bicarbonates; Cytoskeletal Proteins; Female; Guinea Pigs; Islets of Langerhans; Male; Mice; Pancreas; Pancreatic Ducts; Rats; Receptors, Purinergic P1; Rodentia
PubMed: 31717704
DOI: 10.3390/ijms20215329 -
Scientific Reports Oct 2016Magnetic resonance cholangiopancreatography (MRCP), MRCP after secretin stimulation (S-MRCP) and endoscopic ultrasonography (EUS) are all selected to diagnose pancreas... (Meta-Analysis)
Meta-Analysis Review
Magnetic resonance cholangiopancreatography (MRCP), MRCP after secretin stimulation (S-MRCP) and endoscopic ultrasonography (EUS) are all selected to diagnose pancreas divisum. However, the accuracies of three diagnosis remain unclear. The aim is to address the diagnostic accuracies of MRCP, S-MRCP and EUS on pancreas divisum. We searched PubMed, MEDLINE and EMBASE databases from inception to January, 2015. Of the 536 citations retrieved, 16 studies were included. For MRCP diagnosis on pancreas divisum, the area under the hierarchical summary receiver-operating characteristic (HSROC) curve was 0.90 (95% confidence interval [CI] 0.87 to 0.92), and for S-MRCP and EUS, 0.99 (95% CI 0.97 to 0.99) and 0.97 (95% CI 0.96 to 0.98). Sensitivity and specificity for MRCP were 0.59 (95% CI 0.45 to 0.71) and 0.99 (95% CI 0.96 to 1.00); for S-MRCP, 0.83 (95% CI 0.66 to 0.92) and 0.99 (95% CI 0.96 to 1.00); for EUS, 0.85 (95% CI 0.67 to 0.94) and 0.97 (95% CI 0.90 to 0.99). Comprehensive comparison of three diagnostic techniques to pancreas divisum, S-MRCP was more reliable than MRCP and EUS on the effect of the diagnostic test.
Topics: Adolescent; Adult; Aged; Child; Cholangiopancreatography, Magnetic Resonance; Endoscopy; Endosonography; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Diseases; Pancreatitis; ROC Curve; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography; Young Adult
PubMed: 27734952
DOI: 10.1038/srep35389 -
Developmental Cell Jun 2022Diabetic patients show elevated plasma IL18 concentrations. IL18 has two receptors: the IL18 receptor (IL18r) and the Na-Cl co-transporter (NCC). Here, we report that...
Diabetic patients show elevated plasma IL18 concentrations. IL18 has two receptors: the IL18 receptor (IL18r) and the Na-Cl co-transporter (NCC). Here, we report that IL18 is expressed on islet α cells, NCC on β cells, and IL18r on acinar cells in human and mouse pancreases. The deficiency of these receptors reduces islet size, β cell proliferation, and insulin secretion but increases β cell apoptosis and exocrine macrophage accumulation after diet-induced glucose intolerance or streptozotocin-induced hyperglycemia. Together with the glucagon-like peptide-1 (GLP1), IL18 uses the NCC and GLP1 receptors on β cells to trigger β cell development and insulin secretion. IL18 also uses the IL18r on acinar cells to block hyperglycemic pancreas macrophage expansion. The β cell-selective depletion of the NCC or acinar-cell-selective IL18r depletion reduces glucose tolerance and insulin sensitivity with impaired β cell proliferation, enhanced β cell apoptosis and macrophage expansion, and inflammation in mouse hyperglycemic pancreas. IL18 uses NCC, GLP1r, and IL18r to maintain islet β cell function and homeostasis.
Topics: Animals; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Interleukin-18; Mice; Pancreas
PubMed: 35675813
DOI: 10.1016/j.devcel.2022.05.013 -
Obesity Facts 2022Ectopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the...
INTRODUCTION
Ectopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the exocrine pancreas has never been explored in this setting. The aim was to investigate the associations between intra-pancreatic fat deposition (IPFD), pancreas size, and pancreatic enzymes.
METHODS
This cross-sectional study recruited individuals with a history of acute pancreatitis and healthy controls. All participants underwent 3T magnetic resonance imaging, from which IPFD, total pancreas volume (TPV), and pancreas diameters (across the head, body, and tail) were measured independently by 2 raters in a blinded fashion. Circulating levels of pancreatic amylase, pancreatic lipase, and chymotrypsin were measured in a fasted state. A series of linear regression analyses was conducted, accounting for possible confounders.
RESULTS
A total of 108 individuals with pancreatitis and 60 healthy controls were studied. There was a statistically significant difference in IPFD (p < 0.001), but not in TPV (p = 0.389), between the groups. In the post-pancreatitis group, IPFD was significantly inversely associated with pancreas tail diameter (β = -0.736, p = 0.036 in the most adjusted model). In the control group, IPFD was significantly inversely associated with TPV (β = -3.557, p = 0.026 in the most adjusted model). Levels of pancreatic amylase were significantly directly associated with pancreas tail diameter in the post-pancreatitis group (β = 3.891, p = 0.042 in the most adjusted model), whereas levels of pancreatic lipase were significantly inversely associated with TPV in the control group (β = -10.533, p = 0.024 in the most adjusted model).
CONCLUSION
Increased IPFD in individuals after an attack of pancreatitis is associated with reduced pancreas tail diameter, which is in turn associated with reduced circulating levels of pancreatic amylase. The relationship between IPFD and the exocrine pancreas warrants further investigations.
Topics: Acute Disease; Cross-Sectional Studies; Humans; Magnetic Resonance Imaging; Pancreas; Pancreatitis
PubMed: 34753126
DOI: 10.1159/000519621 -
Developmental Biology Mar 2018The murine pancreas buds from the ventral embryonic endoderm at approximately 8.75 dpc and a second pancreas bud emerges from the dorsal endoderm by 9.0 dpc. Although it...
The murine pancreas buds from the ventral embryonic endoderm at approximately 8.75 dpc and a second pancreas bud emerges from the dorsal endoderm by 9.0 dpc. Although it is clear that secreted signals from adjacent mesoderm-derived sources are required for both the appropriate emergence and further refinement of the pancreatic endoderm, neither the exact signals nor the requisite tissue sources have been defined in mammalian systems. Herein we use DiI fate mapping of cultured murine embryos to identify the embryonic sources of both the early inductive and later condensed pancreatic mesenchyme. Despite being capable of supporting pancreas induction from dorsal endoderm in co-culture experiments, we find that in the context of the developing embryo, the dorsal aortae as well as the paraxial, intermediate, and lateral mesoderm derivatives only transiently associate with the dorsal pancreas bud, producing descendants that are decidedly anterior to the pancreas bud. Unlike these other mesoderm derivatives, the axial (notochord) descendants maintain association with the dorsal pre-pancreatic endoderm and early pancreas bud. This fate mapping data points to the notochord as the likely inductive source in vivo while also revealing dynamic morphogenetic movements displayed by individual mesodermal subtypes. Because none of the mesoderm examined above produced the pancreatic mesenchyme that condenses around the induced bud to support exocrine and endocrine differentiation, we also sought to identify the mesodermal origins of this mesenchyme. We identify a portion of the coelomic mesoderm that contributes to the condensed pancreatic mesenchyme. In conclusion, we identify a portion of the notochord as a likely source of the signals required to induce and maintain the early dorsal pancreas bud, demonstrate that the coelomic mesothelium contributes to the dorsal and ventral pancreatic mesenchyme, and provide insight into the dynamic morphological rearrangements of mesoderm-derived tissues during early organogenesis stages of mammalian development.
Topics: Animals; Embryo, Mammalian; Mesoderm; Mice; Organogenesis; Pancreas
PubMed: 29329912
DOI: 10.1016/j.ydbio.2018.01.003 -
Diabetologia Aug 2018The numbers of insulin-secreting pancreatic beta cells are reduced in people with type 1 and type 2 diabetes. Driving beta cell regeneration in the pancreases of people... (Review)
Review
The numbers of insulin-secreting pancreatic beta cells are reduced in people with type 1 and type 2 diabetes. Driving beta cell regeneration in the pancreases of people with diabetes would be an attractive approach to reversing diabetes. While adult human beta cells have long been believed to be terminally differentiated and, therefore, irreversibly quiescent, it has become clear over recent years that this is not true. More specifically, both candidate and unbiased high-throughput screen approaches have revealed several classes of molecules that are clearly able to induce human beta cell proliferation. Here, we review recent approaches and accomplishments in human beta cell regenerative drug discovery. We also list the challenges that this rapidly moving field must confront to translate beta cell regenerative therapy from the laboratory to the clinic.
Topics: Diabetes Mellitus, Type 2; Drug Discovery; Humans; Insulin-Secreting Cells; Pancreas; Regeneration
PubMed: 29770834
DOI: 10.1007/s00125-018-4639-6 -
Molecular Metabolism Sep 2017Diabetes mellitus is characterized by loss or dysfunction of insulin-producing β-cells in the pancreas, resulting in failure of blood glucose regulation and devastating... (Review)
Review
BACKGROUND
Diabetes mellitus is characterized by loss or dysfunction of insulin-producing β-cells in the pancreas, resulting in failure of blood glucose regulation and devastating secondary complications. Thus, β-cells are currently the prime target for cell-replacement and regenerative therapy. Triggering endogenous repair is a promising strategy to restore β-cell mass and normoglycemia in diabetic patients. Potential strategies include targeting specific β-cell subpopulations to increase proliferation or maturation. Alternatively, transdifferentiation of pancreatic islet cells (e.g. α- or δ-cells), extra-islet cells (acinar and ductal cells), hepatocytes, or intestinal cells into insulin-producing cells might improve glycemic control. To this end, it is crucial to systematically characterize and unravel the transcriptional program of all pancreatic cell types at the molecular level in homeostasis and disease. Furthermore, it is necessary to better determine the underlying mechanisms of β-cell maturation, maintenance, and dysfunction in diabetes, to identify and molecularly profile endocrine subpopulations with regenerative potential, and to translate the findings from mice to man. Recent approaches in single-cell biology started to illuminate heterogeneity and plasticity in the pancreas that might be targeted for β-cell regeneration in diabetic patients.
SCOPE OF REVIEW
This review discusses recent literature on single-cell analysis including single-cell RNA sequencing, single-cell mass cytometry, and flow cytometry of pancreatic cell types in the context of mechanisms of endogenous β-cell regeneration. We discuss new findings on the regulation of postnatal β-cell proliferation and maturation. We highlight how single-cell analysis recapitulates described principles of functional β-cell heterogeneity in animal models and adds new knowledge on the extent of β-cell heterogeneity in humans as well as its role in homeostasis and disease. Furthermore, we summarize the findings on cell subpopulations with regenerative potential that might enable the formation of new β-cells in diseased state. Finally, we review new data on the transcriptional program and function of rare pancreatic cell types and their implication in diabetes.
MAJOR CONCLUSION
Novel, single-cell technologies offer high molecular resolution of cellular heterogeneity within the pancreas and provide information on processes and factors that govern β-cell homeostasis, proliferation, and maturation. Eventually, these technologies might lead to the characterization of cells with regenerative potential and unravel disease-associated changes in gene expression to identify cellular and molecular targets for therapy.
Topics: Animals; Blood Glucose; Cell Differentiation; Cell Plasticity; Cell Proliferation; Cell Transdifferentiation; Diabetes Mellitus; Humans; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Pancreas; Single-Cell Analysis
PubMed: 28951822
DOI: 10.1016/j.molmet.2017.06.021 -
International Journal of Hyperthermia :... 2023Pancreatic cancer is a malignant disease associated with poor survival and nearly 80% present with unresectable tumors. Treatments such as chemotherapy and radiation...
Pancreatic cancer is a malignant disease associated with poor survival and nearly 80% present with unresectable tumors. Treatments such as chemotherapy and radiation therapy have shown overall improved survival benefits, albeit limited. Histotripsy is a noninvasive, non-ionizing, and non-thermal focused ultrasound ablation modality that has shown efficacy in treating hepatic tumors and other malignancies. In this novel study, we investigate histotripsy for noninvasive pancreas ablation in a pig model. In two studies, histotripsy was applied to the healthy pancreas in 11 pigs using a custom 32-element, 500 kHz histotripsy transducer attached to a clinical histotripsy system, with treatments guided by real-time ultrasound imaging. A pilot study was conducted in 3 fasted pigs with histotripsy applied at a pulse repetition frequency (PRF) of 500 Hz. Results showed no pancreas visualization on coaxial ultrasound imaging due to overlying intestinal gas, resulting in off-target injury and no pancreas damage. To minimize gas, a second group of pigs ( = 8) were fed a custard diet containing simethicone and bisacodyl. Pigs were euthanized immediately ( = 4) or survived for 1 week ( = 4) post-treatment. Damage to the pancreas and surrounding tissue was characterized using gross morphology, histological analysis, and CT imaging. Results showed histotripsy bubble clouds were generated inside pancreases that were visually maintained on coaxial ultrasound ( = 4), with 2 pigs exhibiting off-target damage. For chronic animals, results showed the treatments were well-tolerated with no complication signs or changes in blood markers. This study provides initial evidence suggesting histotripsy's potential for noninvasive pancreas ablation and warrants further evaluation in more comprehensive studies.
Topics: Swine; Animals; Feasibility Studies; Pilot Projects; Pancreas; Pancreatic Neoplasms; Ultrasonography, Interventional
PubMed: 37643768
DOI: 10.1080/02656736.2023.2247187