Search Results (224)

Objectives: Advanced 3D volumetry is increasingly utilized to predict postoperative outcomes. It is widely hypothesized that remnant pancreatic volume and progressive atrophy dictate the loss of endocrine function after pancreaticoduodenectomy (PD). This study aims to investigate this anatomical paradigm by evaluating whether 3D volumetric tissue loss or the baseline metabolic load drives new-onset diabetes mellitus (NODM). Materials and Methods: This retrospective study included 159 non-diabetic patients who underwent PD. Preoperative and postoperative (6-month) computed tomography (CT) images were evaluated using Synapse 3D 6.7 version volumetric analysis software to calculate total pancreas volume, remnant volume, and postoperative progressive atrophy rate. All measured volumes were indexed to body weight. Factors associated with NODM were analyzed using multivariate logistic regression and ROC analysis. Results: Postoperative follow-ups revealed that 30.2% (n = 48) of the patients developed NODM. Interestingly, advanced 3D volumetric analysis revealed no significant differences between the diabetic and non-diabetic cohorts regarding body weight-indexed total pancreas volume, preoperative remnant volume, or postoperative progressive atrophy rate (p = 0.475). Instead, multivariate analysis identified the preoperative metabolic load, represented by Body Mass Index (BMI), as the sole independent predictor of NODM (p = 0.006, OR = 1.125), independent of surgical tissue loss. ROC analysis demonstrated a moderate predictive threshold for BMI > 26.5 kg/m² (AUC = 0.644). Conclusions: In this cohort, the anatomical volume and progressive atrophy of the remnant pancreas, despite precise 3D quantification, were not statistically associated with the development of NODM after PD. Postoperative endocrine failure appears to be strongly associated with the patient’s baseline metabolic stress rather than solely the physical extent of surgical tissue loss. These findings suggest that while anatomical tissue preservation remains biologically important, preoperative metabolic risk stratification should be a clinical priority. Full article

Cats represent a susceptible host and a possible translational model for investigating coronavirus pathogenesis and therapeutics. Recent immunohistochemical (IHC) and histopathological studies in both human and feline tissues have demonstrated SARS-CoV-2 nucleocapsid protein (NP) and spike protein expression within pancreatic islet cells, following a classic temporal infection course. Notably, IHC analysis also reveals NP expression within exocrine ductal epithelial cells. Given that ductal epithelium functions as an islet progenitor pool during tissue injury or metabolic stress, pancreotropic coronaviruses may gain access to the endocrine compartment by exploiting this intrinsic cellular differentiation pathway. Although the precise mechanisms governing intra-islet viral entry remain to be elucidated, this review highlights the capacity of SARS-CoV-2 to compromise both the exocrine (digestive) and endocrine functions of the pancreas. Finally, we evaluate the therapeutic potential of direct-acting antivirals—specifically RNA-dependent RNA polymerase (RdRp) and protease inhibitors—as monotherapies and in synergistic combination to limit pancreatic injury and mitigate the diabetogenic effects of coronaviruses across both acute infection and post-acute sequelae, such as human long-COVID syndrome. Full article

Background: Pancreatoblastoma (PB) is an exceptionally rare malignant epithelial neoplasm of the pancreas that recapitulates the developing pancreatic anlage. It is defined histologically by acinar-predominant differentiation with characteristic squamoid nests, and it may also show ductal and endocrine differentiation within the same tumor, features that distinguish it from acinar cell carcinoma and solid pseudopapillary neoplasm but that are readily overlooked. It occurs predominantly in young children, although adult-onset disease is well documented. We provide a population-based characterization of PB across the full age spectrum and benchmark it against pancreatic ductal adenocarcinoma (PDAC). Methods: Cases diagnosed between 2000 and 2021 were identified in the Surveillance, Epidemiology, and End Results (SEER) 17-registry database using site and histology codes. Cancer-specific survival (CSS) was estimated and compared, and Cox proportional hazards regression was used to explore associations with cancer-specific mortality. Results: Thirty-nine cases of PB were identified, compared with 155,924 cases of PDAC. The median age at diagnosis was 17 years (range, under 1 to 78 years); 12.8% (n = 5) were younger than 1 year. Males accounted for 69.2% (n = 27) of cases. The cohort was divided at the conventional pediatric-to-adult threshold of 18 years into a pediatric subgroup (age < 18 years; n = 20) and an adult subgroup (age ≥ 18 years; n = 19). CSS at 1 and 5 years was 95.0% and 83.5% in the pediatric subgroup, versus 67.7% and 24.6% in the adult subgroup (log-rank p < 0.001). Five-year CSS was 44.8% in males and 75.0% in females. In an exploratory multivariable model, older age was associated with higher cancer-specific mortality both as a dichotomous variable (adjusted hazard ratio [HR] for age ≥ 18 years 10.7, 95% confidence interval [CI] 2.4–48.2; p = 0.002) and, in a parallel model, as a continuous variable (adjusted HR 1.4 per 10-year increment, 95% CI 1.1–1.8; p = 0.002), indicating an age–mortality gradient. Male sex showed an association in the same direction that did not reach statistical significance (adjusted HR 3.3, 95% CI 0.96–11.6; p = 0.06). Relative to PDAC, PB was more frequently diagnosed in males and was associated with markedly superior survival (1- and 5-year CSS 81.8% and 54.9%, versus 28.8% and 4.0%). Conclusions: Pancreatoblastoma is predominantly a malignancy of young males and carries a substantially more favorable prognosis than PDAC, but outcomes differ markedly across the age spectrum, with adult-onset disease showing considerably poorer survival. Translationally, these population-level estimates support age-stratified prognostic counseling, argue for the referral of adults to centers experienced in rare pancreatic tumors, and provide a rationale for prospective molecular profiling to determine whether adult and pediatric PBs are biologically distinct and whether Wnt/beta-catenin pathway activation is therapeutically actionable. Full article

Medimon is an educational role-playing game that integrates visual mnemonics, collectible creatures, disease states, treatment items, and artificial intelligence-powered non-player characters (AI-NPCs) to teach biomedical concepts. This single-arm mixed-methods feasibility pilot examined recruitment, gameplay uptake and progression, player experience, descriptive knowledge outcomes, and AI-NPC interactions during the Medimon endocrine level among high school students. Thirty students consented; 10 generated gameplay data, six completed paired 12-item pretests and posttests, and eight completed a PXI-style survey. Students played independently using a Steam-based build and encountered thyroid, pancreas, and adrenal educational content through exploration, quests, battles, and Medimon collection. Mean paired knowledge scores increased from 19.4% at pretest to 44.4% at posttest, although the change was not statistically significant in this small exploratory sample (p = 0.156). Audiovisual appeal, curiosity, and enjoyment were rated favorably, whereas Progress Feedback was the lowest-rated player-experience domain. Students who completed the posttest demonstrated greater gameplay duration, exploration, quest completion, and Medimon exposure than non-completers. Thematic analysis identified a mismatch between player expectations and AI-NPC scope, including fabricated quests, spatial directions, and game mechanics that introduced unreliable guidance into the educational environment. The study identified barriers related to gameplay uptake, progression feedback, posttest completion, and AI-NPC reliability that should be addressed before the educational efficacy of Medimon is evaluated in a larger controlled study. Full article

Large MAF transcription factors, including MafA and MafB, are essential for maintaining β-cell identity, function and survival. While MafA has been widely studied in pancreas development and type 2 diabetes, the extended roles of MafB in humans are still emerging. During embryogenesis, MafB promotes differentiation of β-cells. While MafB is downregulated in adult mouse β-cells, it remains active in adult human β-cells, indicating important species-specific functions. Mechanistically, MafB cooperates with other β-cell-specific transcription factors, including PDX1, NEUROD1 and NKX6.1, to regulate genes critical for β-cell differentiation and insulin expression. Loss of MafB in human β-cells is associated with hallmark features of diabetic pathology, such as dedifferentiation, impaired insulin production, and transdifferentiation under metabolic stress. In addition to its endocrine roles within islets, MafB regulates macrophage polarization and apoptotic cell clearance, suggesting immune–metabolic interactions that may contribute to islet inflammation and dysfunction. Translationally, MafB may be leveraged to enhance stem-cell-derived β-cell differentiation and maturation and support β-cell identity preservation under stress and potentially immune responses; however, these applications remain to be further studied and validated. In this review, we integrate findings from developmental biology, animal models, and human studies to clarify the overarching role of MafB in bridging β-cell development, immune regulation, and potential translational application in stem-cell therapy or as a biomarker target in diabetes research. Full article

Background: Impaired insulin secretion by pancreatic beta cells drives chronic hyperglycemia, which characterizes type 2 diabetes mellitus. The mechanosensitive ion channel Piezo2 has been implicated in various physiological processes. However, its expression and functional role in pancreatic endocrine cells remain poorly understood. Methods: We investigated the expression, cellular localization, and potential functional significance of Piezo2 in the pancreatic islets of mice fed normal- and high-fat diets (HFD) using molecular, immunohistochemical, and immunofluorescence approaches. Results: Piezo2 mRNA and protein expression were detected in rat pancreatic tissue and the pancreatic beta cell line INS-1 via polymerase chain reaction and Western blotting analyses. Hematoxylin and eosin staining and histopathological analysis were performed to determine the localization of Piezo2, insulin, and glucagon in the islets of Langerhans from mouse pancreas. Immunofluorescence revealed that Piezo2 colocalized with insulin, glucagon, pancreatic polypeptide (PP, a pancreatic cell marker), and insulin/PP (suggesting Ppy-lineage beta cells). Piezo2 expression is significantly reduced in islets from HFD-fed mice and downregulated under high glucose conditions in INS-1 cells. Stretch stimulation, with or without D-GsMTx4 (a Piezo2-specific inhibitor), enhanced glucose-stimulated insulin secretion, whereas ruthenium red (a non-specific Piezo channel inhibitor) did not alter the response to high glucose. Conclusions: These findings demonstrate Piezo2 expression in pancreatic islets and suggest that it is enriched in beta cells and Ppy-lineage beta cells, minority in alpha cells and is responsive to metabolic stress. Although Piezo2 may contribute to beta-cell adaptation, its role in insulin secretion remains unclear. Full article

Variants in the human PAX4 gene are associated with both monogenic and complex forms of diabetes, yet their pathogenic effects remain difficult to define in models that accurately mimic human islet architecture and neonatal metabolic transitions. Here, we created a porcine PAX4 loss-of-function model using CRISPR/Cas9 cytidine deaminase base editing to introduce a premature stop codon in the PAX4 coding sequence. PAX4 knockout piglets developed severe hyperglycemia within 24 h of birth, followed by rapid postnatal clinical deterioration and uniform death by day 3. Biochemical analysis showed significant diabetic decompensation, including electrolyte imbalances, hyperosmolality, azotemia, dyslipidemia, and metabolic acidosis. Gross and histological examinations revealed notable pancreatic hypoplasia with preservation of exocrine tissue. Single-nucleus RNA sequencing and immunohistochemistry demonstrated an almost complete loss of insulin- and somatostatin-producing β- and δ-cells, respectively, with relative preservation of glucagon-expressing α-cells. Overall, these results establish PAX4 as a crucial factor in pancreatic endocrine development and postnatal glucose regulation in a large-animal model. This platform offers a human-relevant system for studying diabetes-associated PAX4 variants and for testing regenerative and gene-based therapies for insulin-deficient diabetes. Full article

Background/Objectives: The present study estimated the potential therapeutic effects of Borassus flabellifer immature endosperm extract (BFE) on the metabolic disorders of diabetes and hypothyroidism using a mixed research design. Methods: Characterization of phytochemicals via GC-MS demonstrated a highly abundant list of bioactive compounds, and it encompassed phenolic derivatives, methylxanthines, fatty acids, and inositol-related compounds. Molecular docking indicated that the major phytoconstituents showed positive binding affinities to the most vital metabolism and endocrine receptors, namely, TRβ1, PPARγ, and AMP-activated protein kinase (AMPK). Notably, both compounds C1 and C2 were highly affined towards TRβ1 (−7.8 and −7.6 kcal/mol), which is attributed to interactions in the active site through hydrogen bonding and hydrophobic responses, which means that the identified compounds were found to have good predicted interactions with some metabolic- and thyroid-associated targets and could be used to form preliminary hypotheses for further mechanistic studies. The in vivo data showed that the disease-induced groups were marked by hyperglycemia, imbalance in thyroid hormones, and dyslipidemia, as well as liver, kidney, and heart dysfunction. BFE caused significant decreases in these changes, which were also observed through improvements in fasting blood glucose, T3, T4, and TSH; partial restoration of lipid profiles; and dampening of liver and kidney injury signalers. The cardiac risk indices were also reduced significantly after BFE administration. Positive changes in body weight gain, feed ratio, and metabolic ratio further reflected better physiological stability. Results: These findings were corroborated by histopathological analysis, which showed that the tissue architecture of the pancreas, liver, kidney, and heart had significantly recovered in the study. BFE still showed constant therapeutic activity even though the magnitude of response was attenuated when combined disease conditions were used. Conclusions: Comprehensively, the results indicate that BFE potentially plays a role in the amelioration of metabolic and endocrine abnormalities of diabetic and hypothyroid conditions. These observations should be regarded as hypothesis-generating, as further mechanistic and translational studies are needed to substantiate their biological relevance. Full article

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review provides a comprehensive summary of current knowledge regarding the role of trace elements: iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in pancreatic physiology and their influence on the pathogenesis of key diseases of this organ, such as diabetes (DM), acute (AP) and chronic pancreatitis (CP), autoimmune pancreatitis (AIP), and pancreatic cancer (PC). Trace elements, including Fe, Cu, Zn, Se, and Mn, play a fundamental role in maintaining endocrine and exocrine homeostasis, participating in insulin synthesis, stabilizing digestive enzymes, and the functioning of antioxidant systems. It has been demonstrated that disturbances in their concentrations lead to the activation of pathological molecular pathways, including oxidative stress, chronic inflammation, and beta-cell apoptosis. In the context of diabetes, excess Fe promotes ferroptosis, whilst exposure to heavy metals such as Cd, Pb, and Hg induces insulin resistance and pancreatic islet dysfunction. In the course of pancreatitis, elements such as Zn and Se exhibit protective potential by stabilizing tissue barriers, whereas toxic metals impair ion transport, exacerbating fibrotic processes. Furthermore, analysis of available data indicates a significant association between heavy metal accumulation and pancreatic carcinogenesis, driven by DNA damage and oncogene modulation. Understanding pancreatic metallomics opens new prospects for early diagnosis, environmental prevention, and the development of targeted therapeutic strategies that restore the body’s micronutrient balance. Full article

The hypothalamic–pituitary–somatotropic (HPS) axis, which includes growth hormone (GH) and insulin-like growth factor 1 (IGF-1), is one of three endocrine systems that show a decline in hormone concentration with age. Among the hypothalamic hormones involved in the aging process, GH-releasing hormone (GHRH) and somatostatin (SST) are most affected, resulting in several age-related changes. The pathophysiology of GH decline in the aging process is unclear, specifically, whether it results from decreased GHRH or increased SST levels. Similarly, it is not known whether quantitative changes in hypothalamic peptides (including SST) precede or follow age-related pathological behavioral changes. SST is produced mainly by cells of the central nervous system (CNS) and the gastrointestinal (GI) tract, which are functionally interconnected systems that undergo significant changes during aging. The physical changes in the aging organism are considered physiological, and experimental evidence indicates that a large proportion of these changes are the result of declining hormonal activity (including the SST system). It is particularly important to understand the role of SST in diseases of old age, which affect both cognitive processes and memory (e.g., Alzheimer’s and Parkinson’s diseases) and the proper functioning of the GI tract and pancreas (e.g., obesity, type 2 diabetes mellitus, and colorectal cancer). This narrative review discusses systemic and peripheral changes in SST production and secretion observed in aging individuals and their potential association with selected diseases of old age, especially CNS and GI tract diseases. Understanding the role of SST expression with age will enable the better application of this neuropeptide in the diagnosis and treatment of diseases of old age (including cancers). Full article

Background/Objectives: Early transient endocrine dysfunction after simultaneous pancreas-kidney transplantation (SPK) frequently triggers urgent investigations to exclude thrombosis, pancreatitis, or rejection, yet many recipients recover during the index admission. We tested whether pre-transplant day zero (D0) serum Fourier-transform infrared spectroscopy (FTIRS) captures a biochemical fingerprint associated with a Start&Stop trajectory (initial insulin independence followed by transient dysfunction with recovery). Methods: In a single-center retrospective case-control study nested within 104 consecutive SPK recipients with available D0 serum, 12 Start&Stop cases were matched 1:1 to 12 No-Stop controls. Serum FTIR spectra went through structured quality control and standardized preprocessing. A Naïve Bayes classifier with Fast Correlation-Based Filter (FCBF) feature selection was evaluated using leave-one-out cross-validation (LOOCV) and label-permutation analysis. Results: Under LOOCV, the primary FTIRS model (Savitzky-Golay second derivative; 600–900 and 2800–3400 cm⁻¹) achieved excellent discrimination (ROC-AUC 1.00) with accuracy 0.958 and F1 score 0.958. Discrimination collapsed under label permutation (ROC-AUC 0.461), supporting a non-random label-spectrum association. Discriminant information mapped mainly to carbohydrate/glycoprotein-associated bands (~946–1161 cm⁻¹), protein structural contributions near the amide III region (~1300 cm⁻¹), and lipid/protein stretching modes (~2865–3163 cm⁻¹), consistent with a multicomponent systemic biochemical state. Conclusions: In this exploratory matched case-control cohort, pre-transplant D0 serum FTIRS signatures were associated with the subsequent Start&Stop phenotype after SPK. These findings should be interpreted as recipient-side exploratory risk-stratification signals rather than clinically actionable decision tools. Larger multicenter validation in unselected cohorts, with standardized endpoint adjudication, preanalytical control, fully nested model development and inter-instrument harmonization, is required before clinical implementation or population-level risk calibration. Full article

Hexavalent chromium, a widespread heavy metal, induces apoptosis via the mitochondrial pathway through Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) proteins. Hypericum perforatum, rich in antioxidants, can neutralise free radicals. This study investigated the effects of CrVI on the pancreas and the protective role of Hypericum perforatum. Five groups of animals were used: control, Cr (CrVI for 3 months), CrH (CrVI + 2.5% Hypericum perforatum extract made from flowers, for 3 months), Cr2 (CrVI for 3 months + distilled water for 1 month), and CrH2 (CrVI for 3 months + Hypericum perforatum extract for 1 month). Samples were collected for histological analysis, gene expression (qRT-PCR), and blood glucose level analysis. CrVI exposure (Cr, Cr2) caused pancreatic damage: oedema, reduced islet size, endocrine cell vacuolisation, and endothelial swelling. Lesions were milder in CrH, while CrH2 resembled the control group. The Bax/Bcl2 ratio increased under CrVI (highest in Cr2), indicating apoptosis, but decreased toward control values in CrH and CrH2. Blood glucose levels confirmed these findings. CrVI proved toxic to the endocrine pancreas, inducing structural and molecular alterations that impaired carbohydrate metabolism. Administration of Hypericum perforatum extract reduced these effects, confirming its antioxidant action and potential as a protective agent against CrVI-induced oxidative stress. Full article

Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: A cross-sectional study was conducted at PIMS Hospital, Islamabad, involving 62 adult patients with homozygous or HbE beta-thalassemia receiving regular blood transfusions. Iron overload was assessed using serum ferritin (SF) and transferrin saturation (TS), while endocrine function was evaluated through measurements of thyroid-stimulating hormone-sensitive (TSH), free thyroxine (FT4), and insulin-like growth factor-1 (IGF-1). Data was analyzed using SPSS v26.0 and R v4.3.1, which included Pearson correlation, chi-square testing, and multivariable regression to explore associations between iron indices and endocrine dysfunction. Results: Serum ferritin demonstrated significant negative correlations with FT4 (r = −0.348, p = 0.005) and IGF-1 (r = −0.302, p = 0.015). MRI T2* pancreas values correlated positively with FT4 (r = 0.268, p = 0.037) and IGF-1 (r = 0.312, p = 0.015). Patients with ferritin > 5000 ng/mL exhibited a higher prevalence of low IGF-1 levels (89.2% vs. 64.0%, p = 0.018). No significant gender-based differences were observed in endocrine parameters. Conclusion: Pancreatic iron burden and elevated serum ferritin were significantly associated with impaired thyroid and growth axis function, highlighting the value of integrating MRI T2* and biochemical markers for early endocrine risk stratification in adult TDT patients. Full article

Energy homeostasis arises from a complex interplay between gut-derived hormones, the central nervous system, and pancreatic function. Beyond the classical incretin axis, a broad spectrum of gut peptides acts in concert to coordinate appetite regulation, nutrient sensing, gastric motility, and systemic bioenergetic balance. Perturbation of this network contributes to metabolic disorders such as obesity, type 2 diabetes, and cachexia, underscoring its pivotal role in physiological and pathological energy regulation. This review provides an integrated analysis of the mechanisms through which gut–brain–pancreas communication maintains metabolic homeostasis, with particular attention to the dynamic cross-talk between peripheral endocrine signals and central regulatory circuits. Alterations in these pathways are examined in relation to their impact on energy expenditure and substrate utilisation, alongside recent translational efforts exploiting multi-receptor peptide agonism and combinatorial hormonal modulation to restore metabolic equilibrium. Emerging therapeutic approaches increasingly aim to engage multiple bioenergetic pathways simultaneously, supported by advances in peptide engineering and molecular design. By conceptualising metabolic regulation as a coordinated network rather than a linear hormonal cascade, this article delineates a physiological and translational framework for next-generation interventions targeting bioenergetic dysfunction in human disease. Full article

Background: The regulation of glucose metabolism is contingent on a multifaceted interaction between intestinal absorption, pancreatic endocrine function, and the hepatic response to insulin. Axis disruption contributes to insulin resistance and type 2 diabetes. Methods: This study tested mulberry, bilberry, and black currant extracts individually and in combination in an integrated in vitro gut, pancreas, and liver model. The extracts were phytochemically characterised and tested at optimal concentrations selected through dose–response studies. Results: The combined treatment preserved and enhanced the intestinal barrier, as evidenced by increased tight-junction levels and reduced oxidative stress. In the pancreas, the combination significantly improved cell viability, enhanced insulin and C-peptide secretion, and increased glucokinase expression, indicating improved glucose-sensing function. In the liver, the combined treatment synergistically activated insulin signalling, increasing the expression of IRS1, GLUT2, AMPK, AKT, and PGC-1α. This resulted in increased glucose absorption, glycogen synthesis, and a marked reduction in extracellular glucose levels under hyperglycaemic conditions. The results show that combining mulberry, bilberry, and blackcurrant produces additive benefits for intestinal barrier integrity and synergistically modulates key elements of hepatic insulin signalling. Conclusions: These findings support a mechanistic rationale for exploring multi-targeted nutraceutical formulations as complementary approaches to modulating processes involved in glycaemic regulation. Full article