scholarly journals Mechanisms of Post-Pancreatitis Diabetes Mellitus and Cystic Fibrosis-Related Diabetes: A Review of Preclinical Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Eleonóra Gál ◽  
Jurij Dolenšek ◽  
Andraž Stožer ◽  
László Czakó ◽  
Attila Ébert ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chronic Pancreatitis ◽  
Exocrine Pancreas ◽  
Endocrine Pancreas ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Endocrine Function ◽  
Preclinical Studies ◽  
Reciprocal Effects ◽  
Acute And Chronic Pancreatitis

Anatomical proximity and functional correlations between the exocrine and endocrine pancreas warrant reciprocal effects between the two parts. Inflammatory diseases of the exocrine pancreas, such as acute or chronic pancreatitis, or the presence of cystic fibrosis disrupt endocrine function, resulting in diabetes of the exocrine pancreas. Although novel mechanisms are being increasingly identified, the intra- and intercellular pathways regulating exocrine–endocrine interactions are still not fully understood, making the development of new and more effective therapies difficult. Therefore, this review sought to accumulate current knowledge regarding the pathogenesis of diabetes in acute and chronic pancreatitis, as well as cystic fibrosis.

scholarly journals EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Jie-hui Tan ◽  
Rong-chang Cao ◽  
Lei Zhou ◽  
Zhi-tao Zhou ◽  
Huo-ji Chen ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Acinar Cell ◽  
Cell Apoptosis ◽  
Inflammatory Diseases ◽  
Inflammatory Injury ◽  
Proteomic Screen ◽  
Apoptosis Pathways ◽  
Induced Apoptosis ◽  
Acute And Chronic Pancreatitis ◽  
Functional Analyses

Abstract Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Human pancreatic tissues including AP, CP, and healthy volunteers were collected during surgery. Humanized PRSS1 (protease serine 1) transgenic (PRSS1Tg) mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qRT-PCR, western blotting, co-immunoprecipitation, immunohistochemistry, and immunofluorescence for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Humanized PRSS1Tg mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. Both EMC6 and APAF1 regulated apoptosis and inflammatory injury in pancreatic inflammatory diseases. Moreover, APAF1 was regulated by EMC6, induced apoptosis to injure acinar cells and promoted inflammation. In the progression of pancreatitis, EMC6 was activated and then upregulated APAF1 to induce acinar cell apoptosis and inflammatory injury. These findings suggest that EMC6 may be a new therapeutic target for the treatment of pancreatic inflammatory diseases.

Effects of gastrointestinal polypeptides on hormone content of endocrine pancreas in the rat

1980 ◽  
Vol 238 (6) ◽  
pp. G526-G530 ◽  
Author(s):  
T. Yamada ◽  
T. E. Solomon ◽  
H. Petersen ◽  
S. R. Levin ◽  
K. Lewin ◽  
...  
Keyword(s):  
Exocrine Pancreas ◽  
Endocrine Pancreas ◽  
Gastric Inhibitory Polypeptide ◽  
Cell Number ◽  
Endocrine Function ◽  
Immunoperoxidase Technique ◽  
Gastrointestinal Peptides ◽  
Pancreatic Endocrine Function ◽  
Delta Cell ◽  
Higher Doses

Although trophic actions of gastrointestinal peptides on exocrine pancreas have been shown, little is known regarding their effects in endocrine pancreas. Therefore, we measured the contents of somatostatin-like immunoreactivity (SLI), insulin and glucagon, in pancreatic extracts from rats that had been treated three times a day for 10 days with saline; 1 microgram/kg caerulein; 5, 25, and 100 microgram/kg secretin; 1 microgram/kg caerulein plus 5, 25, and 100 microgram/kg secretin; 25 microgram/kg pancreatic polypeptide; 15 microgram/kg glicentin; or 15 microgram/kg gastric-inhibitory polypeptide. Pancreatic SLI content was significantly increased in rats treated with glicentin and caerulein plus secretin at the two higher doses. No difference was noted between the control and the caerulein plus 100 microgram/kg secretin groups in delta-cell number per islet when examined by the immunoperoxidase technique. These data suggest that because of their effect on SLI content gastrointestinal polypeptides may modulate pancreatic endocrine function.

scholarly journals Inflammatory diseases of the pancreas: what new do we know about the mechanisms of their development in the 21st century?

2021 ◽  
Vol 93 (1) ◽  
pp. 66-70
Author(s):  
Vadim A. Akhmedov ◽  
Olga V. Gaus
Keyword(s):  
Chronic Pancreatitis ◽  
Tight Junctions ◽  
21St Century ◽  
Genetic Factors ◽  
Inflammatory Diseases ◽  
Adherens Junctions ◽  
Transmembrane Proteins ◽  
Laboratory Diagnostics ◽  
Acute And Chronic Pancreatitis

Inflammatory diseases of the pancreas can range from acute to acute recurrent and chronic pancreatitis. With the improvement of laboratory diagnostics in the 21st century, the mechanisms of the pro-inflammatory and anti-inflammatory role of tight junctions, in particular the transmembrane proteins occludin, claudine and JAMs, cytoplasmic Zo-proteins, and adherens junctions, in particular -catenin, -catenin, E-cadherin, selectins and ICAMs in the pathogenesis of acute and chronic pancreatitis have become more clear. The study of genetic factors in the development of acute and chronic pancreatitis showed the role of mutations in the genes SPINK1 N34S, PRSS1, CEL-HYB in the progression of the disease.

scholarly journals Motion-Genetic Testing is Useful in the Diagnosis of Nonhereditary Pancreatic Conditions: Arguments for the Motion

2003 ◽  
Vol 17 (1) ◽  
pp. 47-52 ◽  
Author(s):  
David C Whitcomb
Keyword(s):  
Cystic Fibrosis ◽  
Chronic Pancreatitis ◽  
Genetic Testing ◽  
Severe Disease ◽  
Bilateral Absence ◽  
Recruitment Bias ◽  
Increased Risk ◽  
Cationic Trypsinogen ◽  
Disease Modifier ◽  
Acute And Chronic Pancreatitis

Mutations of three major genes are associated with an increased risk of acute and chronic pancreatitis: the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the pancreatic secretory trypsin inhibitor (PSTI) or serine protease inhibitor, Kazal type 1 (SPINK1) gene. Some autosomal dominant forms of hereditary pancreatitis are associated with mutations of thePRSS1gene, which can be readily identified by genetic testing. Mutations of theCFTRgene can lead either to cystic fibrosis or to idiopathic chronic pancreatitis, and to a variety of cystic fibrosis-associated disorders, including congenital bilateral absence of the vas deferens and sinusitis. These mutations, as with those of theSPINK1(orPSTI) gene, are prevalent in North America; thus, the presence of such a mutation in an asymptomatic person does not confer a high risk of developing pancreatitis. Combinations of mutations of thePRSS1andSPINK1genes lead to more severe disease, as indicated by an earlier onset of symptoms, which suggests thatSPINK1is a disease modifier. The major fear expressed by potential candidates for genetic testing is that the results could lead to insurance discrimination. Studies of the positive predictive value of genetic tests are hampered by recruitment bias and lack of knowledge of family history of pancreatitis. Genetic testing is most useful for persons for whom family members have already been found to exhibit a particular pancreatitis-associated mutation. In the future, increased knowledge of the myriad genetic causes of pancreatitis, as well as advances in the diagnosis and treatment of early chronic pancreatitis, should enhance the utility of genetic testing.

EMC6 and APAF1 Promote Acinar Cell Injury in Acute and Chronic Pancreatitis

2020 ◽  
Author(s):  
Jie-hui Tan ◽  
Rong-chang Cao ◽  
Lei Zhou ◽  
Zhi-tao Zhou ◽  
Huo-ji Chen ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Acinar Cell ◽  
Cell Injury ◽  
Acute And Chronic Pancreatitis

scholarly journals Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis

Pancreas ◽  
2018 ◽  
Vol 47 (10) ◽  
pp. 1200-1207 ◽  
Author(s):  
Christopher E. Forsmark ◽  
Dana K. Andersen ◽  
John T. Farrar ◽  
Megan Golden ◽  
Aida Habtezion ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Chronic Pancreatitis ◽  
Acute And Chronic Pancreatitis

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

scholarly journals Antimalarial drugs—are they beneficial in rheumatic and viral diseases?—considerations in COVID-19 pandemic

2021 ◽  
Author(s):  
Bogna Grygiel-Górniak
Keyword(s):  
Connective Tissue ◽  
Viral Infections ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Antiviral Drugs ◽  
In Vivo Studies ◽  
Viral Diseases ◽  
Cardiac Complications

AbstractThe majority of the medical fraternity is continuously involved in finding new therapeutic schemes, including antimalarial medications (AMDs), which can be useful in combating the 2019-nCoV: coronavirus disease (COVID-19). For many decades, AMDs have been widely used in the treatment of malaria and various other anti-inflammatory diseases, particularly to treat autoimmune disorders of the connective tissue. The review comprises in vitro and in vivo studies, original studies, clinical trials, and consensus reports for the analysis, which were available in medical databases (e.g., PubMed). This manuscript summarizes the current knowledge about chloroquine (CQ)/hydroxychloroquine (HCQ) and shows the difference between their use, activity, recommendation, doses, and adverse effects on two groups of patients: those with rheumatic and viral diseases (including COVID-19). In the case of connective tissue disorders, AMDs are prescribed for a prolonged duration in small doses, and their effect is observed after few weeks, whereas in the case of viral infections, they are prescribed in larger doses for a short duration to achieve a quick saturation effect. In rheumatic diseases, AMDs are well tolerated, and their side effects are rare. However, in some viral diseases, the effect of AMDs is questionable or not so noticeable as suggested during the initial prognosis. They are mainly used as an additive therapy to antiviral drugs, but recent studies have shown that AMDs can diminish the efficacy of some antiviral drugs and may cause respiratory, kidney, liver, and cardiac complications.

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