Exocrine Cells Research Articles

Lipid storage disease in 4 sibling superb birds-of-paradise (Lophorina superba).

Pedigree analysis, clinical, gross, microscopic, ultrastructural, and lipidomic findings in 4 female superb bird-of-paradise (SBOP, Lophorina superba) siblings led to the diagnosis of a primary inherited glycerolipid storage disease. These birds were the offspring of a related breeding pair (inbreeding coefficient = 0.1797) and are the only known SBOPs to display this constellation of lesions. The birds ranged from 0.75 to 4.3 years of age at the time of death. Two birds were euthanized and 1 died naturally due to the disease, and 1 died of head trauma with no prior clinical signs. Macroscopic findings included hepatomegaly and pallor (4/4), cardiac and renal pallor (2/4), and coelomic effusion (1/4). Microscopic examination found marked tissue distortion due to cytoplasmic lipid vacuoles in hepatocytes (4/4), cardiomyocytes (4/4), renal tubular epithelial cells (4/4), parathyroid gland principal cells (2/2), exocrine pancreatic cells (3/3), and the glandular cells of the ventriculus and proventriculus (3/3). Ultrastructurally, the lipids were deposited in single to coalescing or fused droplets lined by an inconspicuous or discontinuous monolayer membrane. Lipidomic profiling found that the cytoplasmic lipid deposits were primarily composed of triacylglycerols. Future work, including sequencing of the SBOP genome and genotyping, will be required to definitively determine the underlying genetic mechanism of this disease.

Correlation between inflammation, vascularization, adipocyte percentage and exocrine cell percentage at the resection margin and the postoperative pancreatic fistula rate after distal pancreatectomy – a pilot study

Correlation between inflammation, vascularization, adipocyte percentage and exocrine cell percentage at the resection margin and the postoperative pancreatic fistula rate after distal pancreatectomy – a pilot study

FRI657 Case Series On GLP-1 Receptor Agonist Related Acute Pancreatitis

Abstract Disclosure: A.U. Kulkarni: None. V. Mehta: None. M. Renzu: None. K. Pereira: None. M.A. Rather: None. Introduction: Acute pancreatitis (AP) has now become one of the leading causes of GI related hospital admissions in the United States. With increasing use of GLP-1 Receptor Agonists (GLP-1 RA) in T2DM and obesity, they are now being identified as one such class of drugs which can cause AP. We present this case series to discuss these adverse effects. Case 1: A 50 yo AA male with a history of T2DM and hypertension presented with acute severe epigastric pain, nausea and vomiting for 5 days. Vitals were stable. On physical exam, tenderness in the RUQ was noted. Labs revealed lipase of 313 U/l (11-82 U/l), BG of 213 mg/dL, HbA1c 11.3, normal LFT and lipid panel. Blood EtOH was negative. He denied tobacco, alcohol, and illicit drug use. CT abdomen showed acute interstitial edematous pancreatitis without cholelithiasis or choledocholithiasis. Liver ultrasound showed hepatic steatosis. He noted recent initiation of Semaglutide 6 months ago which was stopped 3 weeks prior to this visit due to abdominal discomfort. Previous Dulaglutide therapy was also discontinued due to GI intolerance. Home medication for DM otherwise included metformin and basal insulin. Case 2: A 68 yo AA woman with a history of T2DM, hypothyroidism presented after a week of severe epigastric pain, radiating to her back, with nausea and vomiting. Labs showed lipase 593 U/l (11-82 U/l), BG of 427 mg/dl, HbA1c of 10. Social history was non-contributory. CT Abdomen showed AP and no gallstones or bile duct dilatation. LFTs and lipid panel were unremarkable. Chart review noted prior admission for AP a month ago. Her home medications were basal Insulin and Dulaglutide (4 yrs). Drug induced AP from Dulaglutide was suspected. Lack of clinical improvement after 3 days of management prompted RUQ ultrasound, which was prematurely terminated due to pain during the scan. Subsequent CCK-HIDA was negative for acute cholecystitis but noted low gallbladder EF. Thus dulaglutide was identified as a potential trigger along with gallbladder dysmotility as a possible etiology for her recurrent AP. Both patients were managed with IV fluids, NPO diet and morphine. They were instructed to stop GLP-1 RA and discharged with PCP follow-up. Discussion: GLP-1 RA are now being widely used due to low risk of hypoglycemia and weight loss. Clinical trials with GLP-1 RA have shown mild, asymptomatic increase in lipase, amylase levels as well as rare incidences of AP. This has been attributed to the stimulation of pancreatic beta cells and exocrine duct cells leading to acinar cell hypertrophy, proinflammatory cytokine induction, causing pancreatic injury. Though drug-induced AP is uncommon and is a diagnosis of exclusion, detailed history taking, medication review and investigating for all other causes is of utmost importance. A good understanding of the drugs associated with AP should alert the physician to identify these agents and promptly discontinue them to prevent further complications. Presentation: Friday, June 16, 2023

Fusion pore dynamics of large secretory vesicles define a distinct mechanism of exocytosis.

Exocrine cells utilize large secretory vesicles (LSVs) up to 10 μm in diameter. LSVs fuse with the apical surface, often recruiting actomyosin to extrude their content through dynamic fusion pores. The molecular mechanism regulating pore dynamics remains largely uncharacterized. We observe that the fusion pores of LSVs in the Drosophila larval salivary glands expand, stabilize, and constrict. Arp2/3 is essential for pore expansion and stabilization, while myosin II is essential for pore constriction. We identify several Bin-Amphiphysin-Rvs (BAR) homology domain proteins that regulate fusion pore expansion and stabilization. We show that the I-BAR protein Missing-in-Metastasis (MIM) localizes to the fusion site and is essential for pore expansion and stabilization. The MIM I-BAR domain is essential but not sufficient for localization and function. We conclude that MIM acts in concert with actin, myosin II, and additional BAR-domain proteins to control fusion pore dynamics, mediating a distinct mode of exocytosis, which facilitates actomyosin-dependent content release that maintains apical membrane homeostasis during secretion.

The plasma exosomes from patients with primary Sjögren's syndrome contain epithelial cell-derived proteins involved in ferroptosis.

Primary Sjögren's syndrome (pSS) is an autoimmune disease represented by exocrine gland epithelial cell lesions. However, the mechanism underlying these lesions remains unclear. This study analyzed the plasma exosomes of pSS patients using proteomics and revealed the presence of 24 differentially expressed proteins (DEPs) involved in the primary biological processes and signaling pathways related to ferroptosis. The DEPs enriched in the ferroptosis-related items were represented by downregulated ceruloplasmin (CP) and transferrin (TF). CC analysis of GO enrichment showed that CP and TF were localized at the apical plasma membrane, which is currently found only in epithelial cells. PPI analysis indicated that these exosomal DEPs formed a clustering network containing CP and TF. Among them, C5, C9, Haptoglobin (HP), and SERPING1 interacted directly with CP and TF. Notably, the expression of these proteins significantly decreased in both the pSS and secondary Sjögren's syndrome (sSS) plasma exosomes but not in non-autoimmune sicca syndrome (nSS). In addition, their expression levels were significantly different in the exosomes and plasma. More importantly, the plasma and salivary exosomes of pSS patients contain higher levels of exocrine gland epithelial autoantigens SSA and SSB than those of healthy controls, and epithelial cells with positive labial glands biopsy (LGB) were more susceptible to ferroptosis than those with negative LGB. The results indicated that ferroptosis may be closely related to SS epithelial cell lesions. KEY MESSAGES: • pSS plasma exosomes contain epithelial cell-derived proteins involved in ferroptosis. • Complement C5 and C9 may be new molecules involved in ferroptosis and play a crucial role in pSS epithelial cell pathology. • The serum exosomes from pSS patients, not nSS patients, contain ferroptosis-related proteins. • The changes in the ferroptosis-related protein content in the exosomes can better reflect the state of the epithelial cell lesions than those in the plasma.

Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype

Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with ‘normal’ stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC.

Structural and immunohistochemical characterization of pancreas of Molly fish (Poecilia sphenops), with a special reference to its immune role.

Recently, teleost species have been considered important model systems for investigating different research areas including immunologic one. The available literature provides poor data about the localization and the structure of pancreas in Molly fish. Moreover, little attention has been paid to the immunologic role of pancreatic tissue of teleost, particularly Molly fish; therefore, this study aimed to highlights the description of pancreatic tissue in Molly fish using light- and electron- microscopy, focusing on the role of pancreatic immune cells and pancreatic acinar cells in immune responses. Microscopic analysis revealed that the pancreas of Molly fish was composed of intrahepatic, disseminated and compact parts. Exocrine pancreatic tissue was diffusely extended within the hepatic tissue forming hepatopancreas. The disseminated pancreas appeared as several irregular nodules of pancreatic tissue localized within the mesenteric adipose tissue. The compact pancreas appeared as an oval shaped body embedded within the mesenteric adipose tissue between the spleen and the intestinal loops. Several telocytes and melanomacrophages were detected within the disseminated pancreatic nodules. Moreover, dendritic cells were found in a close association to the exocrine pancreatic acini. The pancreatic acinar cells showed strong immunoreactivity to APG5, TGF-β, IL-1β, NF-κB, Nrf2, and SOX9 in both hepatopancreas and disseminated pancreas of Molly fish. S100 protein revealed a strong expression in the exocrine pancreatic acinar cells of disseminated pancreas and also in the endocrine cells of the compact pancreas. In conclusion, findings of this study suggest the potential role of the pancreas of the Molly fish in cell proliferation and differentiation, proinflammatory cytokines stimulation, and regulation of both innate and adaptive immunity. RESEARCH HIGHLIGHTS: Telocytes and melanomacrophages were detected in the disseminated pancreatic nodules of the Molly fish. In Molly fish, dendritic cells were found in a close association to the exocrine pancreatic acini. Strong immunoreactivity of the pancreatic acinar cells of the Molly fish to APG5, TGF-β, IL-1β, NF-κB, Nrf2, SOX9, and S100.

Pancreatic regional blood flow links the endocrine and exocrine diseases.

An increasing number of studies have demonstrated that disease states of the endocrine or exocrine pancreas aggravate one another, which implies bidirectional blood flow between islets and exocrine cells. However, this is inconsistent with the current model of unidirectional blood flow, which is strictly from islets to exocrine tissues. This conventional model was first proposed in 1932, and it has never to our knowledge been revisited to date. Here, large-scale image capture was used to examine the spatial relationship between islets and blood vessels in the following species: human, monkey, pig, rabbit, ferret, and mouse. While some arterioles passed by or traveled through islets, the majority of islets had no association with them. Islets with direct contact with the arteriole were significantly larger in size and fewer in number than those without contact. Unique to the pancreas, capillaries directly branched out from the arterioles and have been labeled as "small arterioles" in past studies. Overall, the arterioles emerged to feed the pancreas regionally, not specifically targeting individual islets. Vascularizing the pancreas in this way may allow an entire downstream region of islets and acinar cells to be simultaneously exposed to changes in the blood levels of glucose, hormones, and other circulating factors.

Expression and clinicopathological characteristics of PDX1, PTF1A, and SALL4 in large and small ducts of ectopic pancreas located in gastro-duodenum and jejunum

An ectopic pancreas is defined as pancreatic tissue outside its normal location, anatomically separated from the pancreas.The transcription factor pancreas/duodenum homeobox protein 1 (PDX1) is involved in maintaining the pancreas and functions in early pancreatic development, beta cell differentiation, and endocrine non beta cells. Pancreatic transcription factor 1 subunit alpha (PTF1A) affects exocrine cell formation and regulation of acinar cell identity, and is expressed in exocrine cells as a transcription factor. The depletion of SALL4 disrupts self-renewal and induces differentiation.To clarify which of PDX1, PTF1A, or SALL4 determines the difference in Heinrich's classification, we examined the localization and number of positive cells. We analyzed the differential expression of PDX1, PTF1A, and SALL4 in large and small ducts in ectopic pancreas by immunohistochemistry. Results showed that the number of PTF1A-positive cells in large ducts was more widespread in type I than in type II in the gastro-duodenum, and more SALL4-positive cells were noticed in large ducts than in small ducts in the gastro-duodenum of type II. Our results revealed that PTF1A might promote exocrine differentiation in developing the pancreatic tissues, and that those with widespread expression differentiate into exocrine cells.

Morphological description of the pancreas in male and female swan geese

One of the organs that can be found in the abdominal cavity is called the pancreas. It is a vital component in the process by which the food we eat is transformed into fuel for the cells of the body. For investigation of morphological description of the pancreas, the study was performed on twenty adult swan geese (10 males and 10 females). According to the morphological findings, the pancreas of geese was located on the right side of their abdominal cavity. It possessed four lobes—dorsal, splenic, ventral, and third and a distinctive duodenal papilla. It was between the ascending and descending duodenal loops. The goose pancreas has a thin covering of connective tissue over its mesothelium. The pancreatic parenchyma was divided by connective tissue septa, into numerous lobules, and these lobules extended outward from the pancreatic capsule. There was a wide range of diameters for the blood vessels. It consists of significant blood arteries, which can be identified by their oval or circular, bright nuclei. They have oval or circular, brilliant nuclei with the nucleolus. In the swan goose, serous acini and islets of Langerhans made up most of the pancreatic parenchyma. Exocrine cells had pyramidal shapes, acidophilic granules, and serous acini. In conclusion, the pancreas of geese like the most bird and is different from domestic animals.

Pharmacological inhibition of human EZH2 can influence a regenerative β-like cell capacity with in vitro insulin release in pancreatic ductal cells

BackgroundTherapeutic replacement of pancreatic endocrine β-cells is key to improving hyperglycaemia caused by insulin-dependent diabetes . Whilst the pool of ductal progenitors, which give rise to the endocrine cells, are active during development, neogenesis of islets is repressed in the human adult. Recent human donor studies have demonstrated the role of EZH2 inhibition in surgically isolated exocrine cells showing reactivation of insulin expression and the influence on the H3K27me3 barrier to β-cell regeneration. However, those studies fall short on defining the cell type active in transcriptional reactivation events. This study examines the role of the regenerative capacity of human pancreatic ductal cells when stimulated with pharmacological inhibitors of the EZH2 methyltransferase.ResultsHuman pancreatic ductal epithelial cells were stimulated with the EZH2 inhibitors GSK-126, EPZ6438, and triptolide using a 2- and 7-day protocol to determine their influence on the expression of core endocrine development marker NGN3, as well as β-cell markers insulin, MAFA, and PDX1. Chromatin immunoprecipitation studies show a close correspondence of pharmacological EZH2 inhibition with reduced H3K27me3 content of the core genes, NGN3, MAFA and PDX1. Consistent with the reduction of H3K27me3 by pharmacological inhibition of EZH2, we observe measurable immunofluorescence staining of insulin protein and glucose-sensitive insulin response.ConclusionThe results of this study serve as a proof of concept for a probable source of β-cell induction from pancreatic ductal cells that are capable of influencing insulin expression. Whilst pharmacological inhibition of EZH2 can stimulate secretion of detectable insulin from ductal progenitor cells, further studies are required to address mechanism and the identity of ductal progenitor cell targets to improve likely methods designed to reduce the burden of insulin-dependent diabetes.

Histological Features of Different Organs Before and After Treatment of Diabetes by Using Avocado Extract in Rats

Aim of the study: The present study aimed to study histological features of different organs before and after treatment of diabetes by using avocado extract in rats. Materials and methods: Hot aqueous extraction of avocado was performed. Forty male rats (weighted 140–190g) were used in this study. Following the time of acclimatization, the animals had an overnight fast of 18 hours before being prepped for alloxan monohydrate-induced diabetes. Before and after induction, measurements of the animals' body weights and blood glucose levels were made. However, rats received an IP injection of alloxan 150 mg/kg bw. Following that, the rats' blood glucose levels were tracked every day for 3 weeks to establish a stable levels of blood glucose. The animals were divided into 4 groups: Group 1 got water as a non-induced (negative control) condition. Alloxan-induced rats in Group 2 received water as a positive control. Group 3: Alloxan-induced and aqueous extract-treated animals and Group 4 was only given a 40 g/L dose of the aqueous extract of avocado. Pancreas, livers, as well as kidneys from control, alloxanized, and treated rats were taken at different times, processed and utilized for histological examination after being preserved in 10% formaldehyde till processing and staining. Results: The current results showed a significant difference between different groups especially in G3 at different weeks. However, rats in G2 exhibited depleted islet cells and regions of cell necrosis. The tiny, preserved islet cells (PIL) in diabetic rats treated with extract after 1 week (G3) were an improvement as compared with rats at G2. As the days advanced, more improvements were seen in the pancreatic architecture of the rats treated with extract, including the presence of more noticeable islet cells and exocrine cells. As seen by the intact pancreatic islet in G3, caused the healing of the pancreatic tissue after 3 weeks of treatment by extracts. Alloxanized rats (G2) showed the presence of cell necrosis as well as infiltrations of inflammatory cells. However, as the course of therapy continued, it became clear that the tissue architecture had improved, and more glomeruli were seen as well as fewer inflammatory cells (G3). Livers of rats in (G2) showed visible cell necrosis, when compared to the histology of G1 and G4. After receiving medication, rats in group G3 had compact, healthy liver tissues after three weeks. In conclusion, the pancreas, kidneys, and liver were all protected by the avocado extract and showed enhancement in the histological architecture and glucose levels. KEY WORDS: Diabetes, Avocado, Histology, Rats.

The Regulated Secretion and Models of Intracellular Transport: The Goblet Cell as an Example.

Transport models are extremely important to map thousands of proteins and their interactions inside a cell. The transport pathways of luminal and at least initially soluble secretory proteins synthesized in the endoplasmic reticulum can be divided into two groups: the so-called constitutive secretory pathway and regulated secretion (RS) pathway, in which the RS proteins pass through the Golgi complex and are accumulated into storage/secretion granules (SGs). Their contents are released when stimuli trigger the fusion of SGs with the plasma membrane (PM). In specialized exocrine, endocrine, and nerve cells, the RS proteins pass through the baso-lateral plasmalemma. In polarized cells, the RS proteins secrete through the apical PM. This exocytosis of the RS proteins increases in response to external stimuli. Here, we analyze RS in goblet cells to try to understand the transport model that can be used for the explanation of the literature data related to the intracellular transport of their mucins.

Effect Of Gentamicin And Neomycin+Bacitracin On Deoxyribonuclease Activity I On The Quality Of Human DNA Of Salivary Origin

Deoxyribonucleic acid (DNA) can be found in saliva and various other sources. Saliva contains epithelial cells and leukocytes that are released into the oral cavity. Cells in saliva are potential sources of DNA for diagnostic purposes. DNA in saliva can be degraded due to the activity of deoxyribonuclease (DNase), an enzyme that catalyzes the hydrolysis of DNA. DNase I is expressed in exocrine cells while DNase II is expressed in macrophages. Inhibition of DNase activity will preserve DNA. Besides being able to kill bacteria, aminoglycosides (i.e. gentamicin and neomycin) can inhibit DNase. Saliva was collected from 8 subjects. Furthermore, saliva samples from each subject were divided into 4 groups, namely negative control (K1), positive control (K2), gentamicin (K3), and neomycin + bacitracin (K4). DNA was extracted from saliva using the spin column method. DNA from groups K3 and K4 were added to 1 mg/mL gentamicin and 20 mM neomycin + bacitracin, respectively, before adding 2.5 g/mL DNase I (DNA degradation assay). The quality of human genomic DNA from saliva was determined by the presence of the NOTCH2 gene amplicons (~704 bp). DNA was separated by 1% agarose gel electrophoresis and recorded using the gel documentation system. The DNA extracted from saliva using the spin column method had an average concentration of 26.49 + 30.70 ng/mL and an average purity of 1.819 + 0.122. The administration of distilled water as a negative control in the DNA degradation assay showed that no DNA was digested.

MIOEPITHELIAL CELLS: STRUCTURE, FUNCTION, AND THEIR ROLE IN NORMAL AND NEOPLASTIC TRANSFORMATION OF THE BREAST

Abstract. Myoepithelial cells (MECs) are characteristic of exocrine glands and are responsible for synthesizing the extracellular matrix, particularly the structural components of the basal membrane. MECs are of epithelial origin and exhibit contractile function, which aids in milk ejection from the ducts during lactation. Scientific literature suggests that MECs act as suppressors of tumors and play an important diagnostic role in mammary gland pathology, especially in distinguishing diff erent neoplastic processes.Research objective: T o elucidate the histological features and immunohistochemical verifi cation of myoepithelial cells in normal breast tissue and their role in neoplastic transformation of the mammary gland.Materials and Methods. The histological examination of myoepithelial cells of the mammary gland was conducted on archival slides from the Department of Histology, Cytology, and Embryology, Danylo Halytsky Lviv National Medical University. Histological sections, stained with hematoxylin and eosin, as well as immunohistochemical markers p63 (Clone 4A4, Masterdiagnostica) and cytokeratin 5/6Ab-2 (D5/16 B4, Thermoscientifi c) for confi rming the myoepithelial origin of the cells, were analyzed under a light microscope (UlabXSP-137TLED) with 10x and 40x objectives and a 10x eyepiece. Photographs were taken using an XCAM 1080P camera.Research Results. The structural units of the mammary gland (MG) are ductal-l obular formations, the terminal portions of which have an alveolar shape and are formed by secretory exocrine cells with underlying myoepithelial cells – basket-like cells. Identifi cation of myoepithelial cells using conventional histological staining techniques such as hematoxylin and eosin does not always provide a clear understanding of their topography. All myoepithelial cells are located on the basal membrane and contribute to the synthesis of its components (laminin, entactin, etc.). The myoepithelial cell layer, which is consistently present in the normal mammary gland, can appear diff erently: resembling smooth muscle or epithelioid cells, having a stellate or spindle- shaped form, or not being visualized at all. It has been shown that p63 is a sensitive and specifi c nuclear myoepithelial marker, expressed in myoepithelial cells of the normal mammary gland, in residual lobular acini, sclerosing adenosis, carcinoma in situ, and not detected in invasive carcinomas. It can be included in immunohistochemical panels aimed at identifying myoepithelial cells in diagnostically challenging breast pathologies.Conclusions. Myoepithelial cells in the mammary glands play a key role in their function, facilitating the process of milk secretion. However, in certain cases, they also play an important role in the development of neoplastic transformations. Intercellular connections between secretory and myoepithelial cells indicate that the last ones suppress both the progression of carcinoma in situ to invasive breast cancer and the carcinomainduced angiogenesis. The use of the immunohistochemical marker p63 is mandatory in the panel of antibodies to identify myoepithelial cells in the mammary gland and diff erentiate between benign and malignant lesions.

Peroxisomes during postnatal development of mouse endocrine and exocrine pancreas display cell-type- and stage-specific protein composition

Peroxisomal dysfunction unhinges cellular metabolism by causing the accumulation of toxic metabolic intermediates (e.g. reactive oxygen species, very -chain fatty acids, phytanic acid or eicosanoids) and the depletion of important lipid products (e.g. plasmalogens, polyunsaturated fatty acids), leading to various proinflammatory and devastating pathophysiological conditions like metabolic syndrome and age-related diseases including diabetes. Because the peroxisomal antioxidative marker enzyme catalase is low abundant in Langerhans islet cells, peroxisomes were considered scarcely present in the endocrine pancreas. Recently, studies demonstrated that the peroxisomal metabolism is relevant for pancreatic cell functionality. During the postnatal period, significant changes occur in the cell structure and the metabolism to trigger the final maturation of the pancreas, including cell proliferation, regulation of energy metabolism, and activation of signalling pathways. Our aim in this study was to (i) morphometrically analyse the density of peroxisomes in mouse endocrine versus exocrine pancreas and (ii) investigate how the distribution and the abundance of peroxisomal proteins involved in biogenesis, antioxidative defence and fatty acid metabolism change during pancreatic maturation in the postnatal period. Our results prove that endocrine and exocrine pancreatic cells contain high amounts of peroxisomes with heterogeneous protein content indicating that distinct endocrine and exocrine cell types require a specific set of peroxisomal proteins depending on their individual physiological functions. We further show that significant postnatal changes occur in the peroxisomal compartment of different pancreatic cells that are most probably relevant for the metabolic maturation and differentiation of the pancreas during the development from birth to adulthood.

Different diabetes

Different diabetes

Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus

In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2Apro) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2Apro, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3+ T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c+ dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.

SnRNA-Seq of Pancreas Revealed the Dysfunction of Endocrine and Exocrine Cells in Transgenic Pigs with Prediabetes.

Diabetes poses a significant threat to human health. Exocrine pancreatic dysfunction is related to diabetes, but the exact mechanism is not fully understood. This study aimed to describe the pathological phenotype and pathological mechanisms of the pancreas of transgenic pigs (PIGinH11) that was constructed in our laboratory and to compare it with humans. We established diabetes-susceptible transgenic pigs and subjected them to high-fat and high-sucrose dietary interventions. The damage to the pancreatic endocrine and exocrine was evaluated using histopathology and the involved molecular mechanisms were analyzed using single-nucleus RNA-sequencing (SnRNA-seq). Compared to wild-type (WT) pigs, PIGinH11 pigs showed similar pathological manifestations to type 2 diabetes patients, such as insulin deficiency, fatty deposition, inflammatory infiltration, fibrosis tissue necrosis, double positive cells, endoplasmic reticulum (ER) and mitochondria damage. SnRNA-seq analysis revealed 16 clusters and cell-type-specific gene expression characterization in the pig pancreas. Notably, clusters of Ainar-M and Endocrine-U were observed at the intermediate state between the exocrine and endocrine pancreas. Beta cells of the PIGinH11 group demonstrated the dysfunction with insulin produced and secret decreased and ER stress. Moreover, like clinic patients, acinar cells expressed fewer digestive enzymes and showed organelle damage. We hypothesize that TXNIP that is upregulated by high glucose might play an important role in the dysfunction of endocrine to exocrine cells in PIGinH11 pigs.

HISTOMORPHOLOGY OF PANCREATIC TISSUE IN MEDAKA FISH (Oryzias javanicus): STUDY OF DIABETIC ANIMAL MODEL DEVELOPMENT

This study aimed to explore the histomorphology of the pancreatic tissue of medaka fish to develop medaka fish as a diabetic animal model. Adult medaka fish were obtained with a body length of 2.53±0.22 cm and a weight of 265.8±25 g. Medaka fish were fixed using Boiun's fixative solution. Macro anatomical observations of the pancreas were conducted using a stereomicroscope. Histological preparations were made according to the Hematoxylin-eosin staining standard procedure. Pancreatic histomorphology of medaka fish was carried out using a light microscope with 100x and 400x magnification. The macro anatomy observations of the pancreas showed the interconnection with several tissues, such as spleen, gallbladder, liver, fat, and intestines. The pancreas was located toward the liver, oversees the intestines, and covered with fat. Pancreatic histomorphological observations showed exocrine cells composed of serous pyramidal acinar cells and endocrine cells (islets of Langerhans). Intralobular and intercalated ducts (ducts of Boll) were composed of simple cuboidal epithelium. This study concluded that the pancreas organ in medaka fish is a single organ, and histomorphologically has both of exocrine and endocrine cells.