Exocrine Dysfunction Research Articles

INVESTIGATION OF GEOSPATIAL DISPARITIES IN CHRONIC PANCREATITIS OUTCOMES.

Chronic pancreatitis (CP) is a fibro-inflammatory disorder characterized by abdominal pain and exocrine and endocrine pancreatic insufficiency resulting in significant morbidity. This study evaluates the impact of geospatial parameters, assessed using the Social Vulnerability Index (SVI), a tool comprising sixteen social attributes, on CP outcomes, including opioid use. We conducted a retrospective analysis of CP patients with available addresses followed at our pancreas center. We reviewed demographics, clinical variables including number of CP flares, local complications, pancreatic function, and healthcare-resource utilization (HRU) including imaging, endoscopic procedures, and surgeries, and outpatient opioid prescriptions measured in morphine milligram equivalents (MME). Regression analysis was performed to assess the association between outcomes and SVI [divided into 4 quartiles (I-IV; IV being most vulnerable]. Among 324 CP patients followed over 8 years, we noted trends of higher dependence on governmental insurance or no insurance among patients in higher SVI quartiles (III/IV vs. I/II) but no differences in demographics, comorbidities, or etiology of CP. In patients residing in more vulnerable SVI quartiles, we noted significantly higher frequency of hospitalizations for CP flares and lower daily MME. Rates of exocrine and endocrine pancreatic dysfunction and HRU were similar across all SVI quartiles. Despite multidisciplinary guideline-based care, residence in the most vulnerable neighborhoods may be associated with less opioid use and more frequent CP flares, suggesting possible inadequate pain control in these patients. These findings should guide prospective investigation of the impact of geospatial social determinants of health in CP and efforts to mitigate the above disparities.

Endocrine pathology in young rabbits with cystic fibrosis

BackgroundCystic fibrosis (CF) is an autosomal recessive genetic disorder caused by loss-of-function mutations in the CF transmembrane conductance regulator gene. CF-related pancreatic lesions are known to cause exocrine dysfunctions such...

Extended pancreatic neck transection during laparoscopic pancreatoduodenectomy can benefit postoperative short-term outcome without influence on remnant pancreatic function: A propensity score-matched comparison in high-volume center

IntroductionDue to the anatomical characteristics of pancreatic duct alignment and pancreatic blood supply, transecting pancreatic neck more to left (EPNT) could theoretically reduce the incidence of postoperative pancreatic fistula (POPF) by leaving the pancreatic duct central in transverse section and the pancreatic stump enough vascularization. Studies revealed that EPNT contributed to the prevention of POPF after pancreatoduodenectomy (PD). However, the impact of EPNT on the remnant pancreatic function was not investigated. Thus, we conducted this study to further explore the impact of EPNT on patients who underwent laparoscopic pancreatoduodenectomy (LPD), including both short-term and long-term prognosis. Material and methodsA retrospective cohort study with 1:1 propensity score-matched comparison of extended and conventional pancreatic neck transection (EPNT vs. CPNT) was conducted in a high-volume pancreatic surgical center. Primary outcome was clinically relevant POPF (CR-POPF), secondary outcomes were textbook outcome (TO), overall and pancreas specific complications, postoperative new-onset diabetes mellitus, and pancreatic exocrine dysfunction. Risk factors for CR-POPF and TO had also been tested by logistic regression analysis. Results233 patients were involved, 153 in EPNT group and 80 in CPNT group. The independent risk factors for CR-POPF were higher BMI (P=0.035), CPNT (P<0.001), perioperative blood glucose changes (P=0.016), and postoperative serum amylase (P=0.026). The predictors for TO were female (P=0.035), no transfusion (P=0.017), EPNT (P<0.001), and perioperative blood glucose changes (P=0.023). After matching, there were 61 patients in each of the two groups. Lower rate of CR-POPF (11.5% vs. 31.1%, P=0.008), lower rate of Clavien-Dindo≥3 complications (6.6% vs. 21.3%, P=0.019), and higher rate of TO (83.6% vs. 55.7%, P<0.001) occurred in EPNT group. The incidence of postoperative new-onset diabetes mellitus and pancreatic exocrine dysfunction did not have statistically significant differences between the two groups. ConclusionEPNT during LPD benefits postoperative short-term outcomes without influence on remnant pancreatic function. Randomized controlled trial with higher level of evidence is needed for further confirm.

Examination of duodenal and colonic microbiome changes in mouse models of acute and chronic pancreatitis

The exocrine pancreas is the main source of digestive enzymes which are released from secretory vesicles of acinar cells into the small intestine. Enzymes, including amylases, proteases and lipases, degrade the ingested food and thus determine the nutritional substrate for the gut microbiota. Acute (AP) and chronic pancreatitis (CP) are associated with a transitional or progressive exocrine pancreatic dysfunction, we analysed in the present study how an experimental induction of pancreatitis in mouse models affects the colonic and duodenal microbiome composition. Evaluation by 16 S rRNA gene sequencing revealed specific microbiome changes in colonic as well as in duodenal samples in different models of AP and CP. Mild acute pancreatitis, which is associated with a transient impairment of pancreatic secretion showed only minor changes in microbial composition, comparable to the ones seen in progressive dysfunctional mouse models of CP. The strongest changes were observed in a mouse model of severe AP, which suggest a direct effect of the immune response on gut microbiome in addition to a pancreatic dysfunction. Our data indicate that highly dysbiotic microbiome changes during pancreatitis are more associated with the inflammatory reaction than with a disturbed pancreatic secretion.

8182 New Mouse Model Mirrors Human MODY8: Opening Doors to Understanding Exocrine-Endocrine Crosstalk in the Diabetic Pancreas

Abstract Disclosure: K. El Jellas: None. V. Salerno: None. L.S. Katz: None. J. Hu: None. G. Fogarty: None. A. Mandal: None. A. DiStefano-Forti: None. D. Scott: None. M. Lowe: None. A. Molven: None. R.N. Kulkarni: None. Maturity-onset diabetes of the young, type 8 (MODY8) is a dominantly inherited form of monogenic diabetes, caused by heterozygous mutations in the carboxyl ester lipase (CEL) gene expressed in pancreatic acinar cells. MODY8 is characterized by chronic pancreatitis and exocrine dysfunction. Despite the intimate anatomical relationship between the endocrine and exocrine pancreas, little is known about the biological components mediating exocrine-endocrine communication in regulating glucose homeostasis. Here, we report a refined mouse model that bears the mutation present in MODY8 patients on one allele, and the humanized normal variable number of tandem repeat (VNTR) of CEL with 16 repeats (16R) on the other, mimicking the genetic make-up seen in MODY8 patients. Examination of glucose homeostasis revealed that inducing stress (e.g. by high-fat diet) leads to glucose intolerance in MODY8/16R mice and a blunted glucose-stimulated insulin-secretion compared to their control littermates. Histopathological analyses demonstrated features of chronic pancreatitis in some pancreatic lobes, including inflammation, acinar atrophy, acinar-to-ductal metaplasia, fibrosis and fat infiltration, mirroring the morphology of the human disease. Moreover, we applied immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) to intact pancreata and found that beta-cell mass was significantly decreased in the MODY8/16R mice, with a large number of islets located within fatty lobes. These results are coupled with comparative proteomics and lipidomic profiling with the aim of understanding the molecular signatures of exocrine and endocrine cells during pathogenesis. In conclusion, we have generated a mouse that recapitulates several features of the exocrine and endocrine phenotype characteristic of human MODY8. This novel model provides a unique opportunity, not possible in humans, to characterize pancreatic endocrine-exocrine communication in a longitudinal manner as a response to diverse environmental stressors. Presentation: 6/2/2024

Roles of distinct nuclear receptors in diabetic cardiomyopathy.

Diabetes mellitus induces a pathophysiological disorder known as diabetic cardiomyopathy and may eventually cause heart failure. Diabetic cardiomyopathy is manifested with systolic and diastolic contractile dysfunction along with alterations in unique cardiomyocyte proteins and diminished cardiomyocyte contraction. Multiple mechanisms contribute to the pathology of diabetic cardiomyopathy, mainly including abnormal insulin metabolism, hyperglycemia, glycotoxicity, cardiac lipotoxicity, endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction, calcium treatment damage, programmed myocardial cell death, improper Renin-Angiotensin-Aldosterone System activation, maladaptive immune modulation, coronary artery endothelial dysfunction, exocrine dysfunction, etc. There is an urgent need to investigate the exact pathogenesis of diabetic cardiomyopathy and improve the diagnosis and treatment of this disease. The nuclear receptor superfamily comprises a group of transcription factors, such as liver X receptor, retinoid X receptor, retinoic acid-related orphan receptor-α, retinoid receptor, vitamin D receptor, mineralocorticoid receptor, estrogen-related receptor, peroxisome proliferatoractivated receptor, nuclear receptor subfamily 4 group A 1(NR4A1), etc. Various studies have reported that nuclear receptors play a crucial role in cardiovascular diseases. A recently conducted work highlighted the function of the nuclear receptor superfamily in the realm of metabolic diseases and their associated complications. This review summarized the available information on several important nuclear receptors in the pathophysiology of diabetic cardiomyopathy and discussed future perspectives on the application of nuclear receptors as targets for diabetic cardiomyopathy treatment.

Advances in cellular and molecular pathways of salivary gland damage in Sjögren's syndrome.

Sjögren's Syndrome (SS) is an autoimmune disorder characterized by dysfunction of exocrine glands. Primarily affected are the salivary glands, which exhibit the most frequent pathological changes. The pathogenesis involves susceptibility genes, non-genetic factors such as infections, immune cells-including T and B cells, macrophage, dendritic cells, and salivary gland epithelial cells. Inflammatory mediators such as autoantibodies, cytokines, and chemokines also play a critical role. Key signaling pathways activated include IFN, TLR, BAFF/BAFF-R, PI3K/Akt/mTOR, among others. Comprehensive understanding of these mechanisms is crucial for developing targeted therapeutic interventions. Thus, this study explores the cellular and molecular mechanisms underlying SS-related salivary gland damage, aiming to propose novel targeted therapeutic approaches.

Immunomodulatory Effects of Yu-Ping-Feng Formula on Primary Sjögren's Syndrome: Interrogating the T Cell Response.

Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining we hypothesized that Chinese medicine formula, Yu-Ping-Feng (YPF) might be a promising candidate for treating primary Sjögren's syndrome (pSS), a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren's syndrome (ESS) that we previously established for YPF formula treatment. YPF therapy ameliorated the ESS pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using co-culture assay and adoptive transfer models, we demonstrated that YPF formula directly restrained effector/memory T cell expansion and differentiation into Th17 and T follicular helper (Tfh) cells, the key subsets in ESS pathogenesis. Importantly, we recruited 20 pSS patients and conducted a pilot study of 8-week therapy of YPF formula. YPF treatment effectively improved fatigue symptoms, exocrine gland functions and reduced serum IgG/IgA levels, while effector T and B cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggested a novel approach to assess the immunomodulatory effects of YPF formula, which may be favorable for patients with autoimmune disorders.

Emerging biologic frontiers for Sjogren's syndrome: Unveiling novel approaches with emphasis on extra glandular pathology.

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

Diabetes mellitus due to reduced insulin secretion and exocrine pancreatic dysfunction in a patient with a mutation in the carboxyl-ester lipase gene outside the VNTR region

Diabetes mellitus due to reduced insulin secretion and exocrine pancreatic dysfunction in a patient with a mutation in the carboxyl-ester lipase gene outside the VNTR region

Impact of Ethno-racial Factors on Clinical Outcomes and Health Care Utilization in Chronic Pancreatitis.

Healthcare disparities adversely affect clinical outcomes in racial and ethnic minorities. Chronic pancreatitis (CP) is a complex disorder, and pressures for time and cost-containment may amplify the disparity for minorities in this condition. This study aimed to assess ethno-racial differences in the clinical outcomes of CP patients cared for at our institution. This is a study of CP patients with available ethno-racial information followed at our pancreas center. We reviewed their demographics, comorbidities, clinical outcomes, and resource utilization: pain, frequent flares (≥ 2/year), local complications, psychosocial variables, exocrine, and endocrine insufficiency, imaging, endoscopic procedures, and surgeries. The outcomes underwent logistic regression to ascertain association(s) with covariates and were expressed as odds ratio (95% confidence intervals). Of the 445 CP patients, there were 23 Hispanics, 330 Non-Hispanic Whites, 47 Non-Hispanic Blacks, 16 Asian Americans, and 29 patients from Other/mixed races. Over a median follow-up of 7years, no significant differences in the pain profile (p = 0.36), neuromodulator use (p = 0.94), and opioid use for intermittent (p = 0.34) and daily pain (p = 0.80) were observed. Frequent flares were associated with Hispanic ethnicity [2.98(1.20-7.36); p = 0.02], despite adjustment for smoking [2.21(1.11-4.41); p = 0.02)] and alcohol [1.88(1.06-3.35); p = 0.03]. Local complications (pseudocysts, mesenteric thrombosis, and biliary obstruction), exocrine and endocrine dysfunction, and healthcare resource utilization (cross-sectional imaging, endoscopic procedures, celiac blocks, or surgeries) were comparable across all ethno-racial groups. Although no significant differences in clinical outcomes, and health resource utilization were noted across ethno-racial groups, Hispanic ethnicity had significant association with CP flares. This study calls for further investigation of an understudied minority population with CP.

A case report on Sjogren syndrome with autoimmune liver disorder

Background: Primary Sjogren’s syndrome (pSS) is a chronic systemic and autoimmune disorder characterized by inflammation and dysfunction of exocrine glands. Liver involvement was the first extraglandular manifestations to be reported in patients with pSS. Tubulointerstitial nephritis (TIN) is the main renal involvement associated with pSS and manifest as distal renal tubular acidosis (RTA), and others, of which RTA is the main clinical presentation. RTA has been reported in 4.3 to 9% of pSS patients. In this case, patient experiences RTA. Case Presentation: A 19 year old female patient was presented with complaints of abdominal pain, fatigue for 2 months and loose stools. She had history of autoimmune hepatitis and decompensated liver cirrhosis with portal hypertension (autoimmune), bilateral peroneal axonal neuropathy, grade II hepatic encephalopathy resolved and recurrent pustular lesion for past 2 years which rupture spontaneously and heals with scary. She also presented with recurrent hypokalemia which was corrected. No history of similar complaints among the family members. Conclusion: This case explains the autoimmune liver disorder with newly diagnosed primary sjogren’s syndrome associated with recurrent hypokalemia.

The Use of Pancreatic Exocrine Insufficiency-Questionnaire (PEI-Q)

Chronic pancreatitis is a non-reversible, progressive inflammatory disease of the pancreas that is caused by repeated inflammation. It is characterized by morphological changes in the parenchyma and main pancreatic duct as pancreatic tissue is damaged and fibrosis progresses. These changes can lead to exocrine and endocrine dysfunction in patients with chronic pancreatitis, with major complications including pain, endocrine or exocrine insufficiency, and increased risk of pancreatic cancer. Of these, pancreatic exocrine insufficiency (PEI) is a state of malabsorption in which more than 15 g of fat is excreted per day. It can be diagnosed and assessed using several methods, but these methods are currently difficult to use in Korea and have low compliance, making them low utility. Recently, the PEI-questionnaire (PEI-Q) was developed to diagnose and assess patients’ exocrine insufficiency. It has been validated in foreign countries and has the potential to be used as a tool for diagnosing exocrine insufficiency with simple questions. This paper will review the diagnostic methods for existing exocrine insufficiency and the usefulness and utilization of the PEI-Q.

Discovery and Verification of Sjögren's Syndrome Protein Biomarkers in Tears by Targeted LC-MRM.

Sjögren's syndrome (SS) is an autoimmune rheumatic disorder characterized by exocrine gland dysfunction, mainly from the lacrimal and salivary glands. The disease causes severe aqueous dry eye syndrome (DED) and is associated with high rates of complications, including corneal ulceration, scaring, and perforation. Systemic complications may occur as well as a higher risk of developing lymphoma. Diagnosis of SS-DED is often delayed and difficult to establish. With the aim of discovering biomarkers to help discriminate SS-DED patients, a combination of untargeted and targeted LC-MS/MS analyses were performed on tear samples collected on Schirmer strips and subjected to tryptic digestion. Following the analysis of three cohorts and the development of two targeted LC-sMRM methods for the verification of putative biomarkers found in the first cohort of samples, 64 proteins could be linked to Sjögren's syndrome, in the hopes of helping to confirm diagnoses as well as potentially stratifying the severity of disease in these patients. Proteins that were increased in SS-DED showed activation of the immune system and alterations in homeostasis. Several proteases and protease inhibitors were found to be significantly changing in SS-DED, as well as a consistent decrease in specific proteins known to be secreted by the lacrimal gland.

Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in Sjogren's syndrome via lipid ROS/pSTAT4/AQP5 axis

Sjogren's syndrome (SS) is an autoimmune disease characterized by dysfunction of exocrine glands, such as salivary glands. However, the molecular mechanism of salivary secretion dysfunction in SS is still unclear. Given the significance of glutathione peroxidase 4 (GPX4) in cellular redox homeostasis, we hypothesized that dysregulation of GPX4 may play a pivotal role in the pathogenesis of salivary secretion dysfunction observed in SS. The salivary gland of SS patients and the SS mouse model exhibited reduced expression of the ferroptosis inhibitor GPX4 and the important protein aquaporin 5 (AQP5), which is involved in salivary secretion. GPX4 overexpression upregulated and GPX4 knockdown downregulated AQP5 expression in salivary gland epithelial cells (SGECs) and salivary secretion. Bioinformatics analysis of GSE databases from SS patients' salivary glands revealed STAT4 as a key intermediary regulator between GPX4 and AQP5. A higher level of nuclear pSTAT4 was observed in the salivary gland of the SS mouse model. GPX4 overexpression inhibited and GPX4 knockdown promoted STAT4 phosphorylation and nuclear translocation in SGECs. CHIP assay confirmed the binding of pSTAT4 within the promoter of AQP5 inhibiting AQP5 transcription. GPX4 downregulation accumulates intracellular lipid ROS in SGECs. Lipid ROS inhibitor ferrostatin-1 treatment during in vitro and in vivo studies confirmed that lipid ROS activates STAT4 phosphorylation and nuclear translocation in SGECs. In summary, the downregulated GPX4 in SGECs contributes to salivary secretion dysfunction in SS via the lipid ROS/pSTAT4/AQP5 axis. This study unraveled novel targets to revitalize the salivary secretion function in SS patients.

Integrated analysis of m6A regulator-mediated RNA methylation modification patterns and immune characteristics in Sjögren's syndrome

The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.

Western diet-induced ultrastructural changes in mouse pancreatic acinar cells.

Mouse models of diet-induced type 2 diabetes mellitus provide powerful tools for studying the structural and physiological changes that are related to the disease progression. In this study, diabetic-like glucose dysregulation was induced in mice by feeding them a western diet, and light and transmission electron microscopy were used to study the ultrastructural changes in the pancreatic acinar cells. Acinar necrosis and vacuolization of the cytoplasm were the most prominent features. Furthermore, we observed intracellular and extracellular accumulation of lipid compounds in the form of lipid droplets, structural enlargement of the cisternae of the rough endoplasmic reticulum (RER), and altered mitochondrial morphology, with mitochondria lacking the typical organization of the inner membrane. Last, autophagic structures, i.e., autophagosomes, autolysosomes, and residual bodies, were abundant within the acinar cells of western diet-fed mice, and the autolysosomes contained lipids and material of varying electron density. While diets inducing obesity and type 2 diabetes are clearly associated with structural changes and dysfunction of the endocrine pancreas, we here demonstrate the strong effect of dietary intervention on the structure of acinar cells in the exocrine part of the organ before detectable changes in plasma amylase activity, which may help us better understand the development of non-alcoholic fatty pancreas disease and its association with endo- and exocrine dysfunction.

Differences in Plasma Fatty Acid Composition Related to Chronic Pancreatitis: A Pilot Study.

Chronic pancreatitis (CP) is an inflammatory disease affecting the absorption of fat-soluble nutrients. Signaling in pancreatic cells that lead to inflammation may be influenced by fatty acids (FAs) through diet and de novo lipogenesis. Here, we investigated the relationship between plasma FA composition in CP with heterogeneity of etiology and complications of CP. Blood and clinical parameters were collected from subjects with CP (n = 47) and controls (n = 22). Plasma was analyzed for FA composition using gas chromatography and compared between controls and CP and within CP. Palmitic acid increased, and linoleic acid decreased in CP compared with controls. Correlations between age or body mass index and FAs are altered in CP compared with controls. Diabetes, pancreatic calcifications, and substance usage, but not exocrine pancreatic dysfunction, were associated with differences in oleic acid and linoleic acid relative abundance in CP. De novo lipogenesis index was increased in the plasma of subjects with CP compared with controls and in calcific CP compared with noncalcific CP. Fatty acids that are markers of de novo lipogenesis and linoleic acid are dysregulated in CP depending on the etiology or complication. These results enhance our understanding of CP and highlight potential pathways targeting FAs for treating CP.

Features of the clinical course of chronic pancreatitis in patients with chronic obstructive pulmonary disease

Aim. The purpose of the study is to determine the intensity of the manifestation of clinical syndromes in the comorbid course of chronic pancreatitis (CP) in patients with chronic obstructive pulmonary disease (COPD) in comparison with the isolated course of CP and to assess the intensity of the mutual burden syndrome. Material and methods. A prospective cohort study was conducted, analyzing the medical records of 212 inpatients. The first group comprised 96 individuals with an isolated course of chronic pancreatitis (CP), while the second group included 116 patients with CP and comorbid chronic obstructive pulmonary disease (COPD), categorized as Group E. The study focused on subjective manifestations of pain syndrome in CP, the extent of exocrine pancreatic insufficiency, clinical blood analysis, biochemical research regarding the content of markers indicating pancreatic enzyme deviation in the blood, and the level of elastase-1 in feces. Additionally, ultrasonographic examination of the organs in the abdominal cavity was performed. Results. Patients in group 2 exhibited manifestations of abdominal pain syndrome 1.2 times more frequently than those in group 1 (p &lt; 0.05). The frequency of pain in the pancreas radiating to the right subcostal region was 1.9 times higher in group 2 compared to group 1 (p &lt; 0.05), along with a 2.1 times increase in the symptom of girdled pain radiating to the back (p &lt; 0.05). Although the frequency of dyspeptic syndrome was slightly higher in group 2 (1.3 times, p &gt; 0.05), astheno-vegetative syndrome was significantly more pronounced, exceeding the frequency in group 1 by 1.7 times (p &lt; 0.05). Ultrasonography parameters of the pancreas in both groups revealed characteristic signs of chronic pancreatitis (CP). The analysis of pancreatic functional state indicators during exacerbation indicated hyperenzymemia syndrome, with α-amylase activity significantly higher in patients of both groups compared to the control group – by 1.8 and 2.6 times, respectively (p &lt; 0.05). Conclusions. CP with chronic obstructive pulmonary disease (COPD) is characterized by a significantly lower frequency of paroxysmal abdominal pain syndrome but a higher frequency of constant aching pain in the pancreas area. Additionally, it is associated with the maximum intensity of inflammation, hyperfermentemia, a decrease in the activity of elastase-1 in feces, and a higher intensity of astheno-vegetative, painful, dyspepsia, intoxication syndromes. Moreover, there is a more pronounced exocrine dysfunction of the pancreas and more significant changes in the sonographic structure of the pancreas compared to cases with the isolated course of CP.

Interactions between the Exocrine and the Endocrine Pancreas.

The pancreas has two main functions: to produce and secrete digestive enzymes (exocrine function) and to produce hormones that regulate blood glucose and splanchnic secretion (endocrine function). The endocrine and exocrine portions of the pancreas are central regulators in digestion and metabolism, with continuous crosstalk between their deeply interconnected components, which plays a role in disease. Pancreatic neoplasms, inflammation, trauma, and surgery can lead to the development of type 3c diabetes when an insult simultaneously damages both acini and islets, leading to exocrine and endocrine dysfunction. In diabetes mellitus patients, pancreatic exocrine insufficiency is highly prevalent, yet little is known about the associations between diabetes mellitus and pancreatic exocrine function. This review aims to provide an overview of the physiology of the pancreas, summarize the pathophysiology and diagnostic work-up of pancreatic exocrine insufficiency, and explore the relationships between exocrine pancreatic insufficiency and diabetes mellitus.