Search Results (66)

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article

Background/Objectives: Duodenum-preserving pancreatic head resection (DPPHR) preserves digestive and absorptive functions better than pancreaticoduodenectomy (PD). Zinc is primarily absorbed in the duodenum and proximal jejunum and plays a critical role in nutritional maintenance and pancreatic regeneration. However, no studies have compared the postoperative pancreatic volume and serum zinc levels between DPPHR and PD. Methods: We retrospectively analyzed 41 patients who underwent DPPHR (n = 23) or subtotal stomach-preserving PD (n = 18) for low-grade pancreatic malignancies at our institution. The remnant pancreatic volumes on postoperative day 7 and 1 year were measured via computed tomography. Nutritional parameters, including serum albumin, prognostic nutritional index (PNI), and serum zinc levels, were compared between the groups. Serum zinc levels were evaluated in patients with DPPHR (n = 11) or PD (n = 7). Results: The DPPHR group demonstrated significantly better preservation of remnant pancreatic volume on postoperative day 7 and 1 year compared to the PD group (p = 0.045 and p = 0.041, respectively). Volume maintenance ratios were also significantly higher in the DPPHR group. Serum albumin levels at 1 year postoperatively were significantly better in the DPPHR group, although no significant difference was found in the PNI. Among patients evaluated for serum zinc, the DPPHR group showed significantly higher zinc levels compared to the PD group (80.3 vs. 65.8 μg/dL, p = 0.017). Conclusions: DPPHR preserves remnant pancreatic volume and maintains serum zinc levels better than PD, potentially contributing to improved postoperative nutritional status and quality of life. Further prospective studies with larger cohorts are warranted to validate these findings. Full article

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells. The regeneration of durable insulin-producing β-cells remains a critical challenge. This study investigated the regenerative potential of Fraction-B (FB), a catfish skin-derived preparation rich in growth factors, in a T1D rat model to regenerate active β-cells. Sprague Dawley rats with T1D caused by streptozotocin injection received daily intraperitoneal injections of FB for 8 weeks. FB treatment significantly reduced blood glucose to a level close to that of normal control animals, increased serum insulin and C-peptide, and restored pancreatic insulin content. Histopathological and immunohistochemical analyses confirmed the regeneration of insulin-producing β-cells in pancreatic islets. FB treatment also improved diabetes-related health issues through a reduction in inflammation and oxidative stress, and an improvement in lipid profiles without toxicity or side effects. The regenerated β-cells remained functional for 48 weeks without the use of immunosuppressants, until the animals were sacrificed. These findings suggest FB treatment to be a promising procedure for translational research into T1D treatment. Full article

Alpha-lipoic acid (ALA) is an essential organosulfur compound with a wide range of therapeutic applications, particularly in conditions involving inflammation and oxidative stress. In this review, we describe our current understanding of the multifaceted role of ALA in several inflammatory diseases (acute pancreatitis, arthritis, osteoarthritis, asthma, and sepsis), cardiovascular disorders (CVDs), and neurological conditions. The dual redox nature of ALA, shared with its reduced form dihydrolipoic acid (DHLA), underpins its powerful antioxidant and anti-inflammatory properties, including reactive oxygen species scavenging, metal chelation, and the regeneration of endogenous antioxidants such as glutathione. A substantial body of evidence from preclinical and clinical studies suggests that ALA modulates the key signaling pathways involved in inflammation and cellular stress responses, making it a promising candidate for mitigating inflammation and its systemic consequences. Notably, we also discuss a novel perspective that attributes some of the therapeutic effects of ALA to its ability to release hydrogen sulfide (H₂S), a gaseous signaling molecule. This mechanism may offer further insights into the efficacy of ALA in the treatment of several diseases. Together, these findings support the potential of ALA as a multifunctional agent for managing inflammatory and oxidative stress-related diseases. Full article

Background: Over the past 40 years since the discovery of regenerating family proteins (Reg proteins), numerous studies have highlighted their biological functions in promoting cell proliferation and resisting cell apoptosis, particularly in the regeneration and repair of pancreatic islets and exocrine glands. Successively, short peptides derived from Reg3δ and Reg3α have been employed in clinical trials, showing favorable therapeutic effects in patients with type I and type II diabetes. However, continued reports have been limited, presumably attributed to the potential side effects. Methods: This review summarizes extensive research on Reg proteins over the past decade, combined with our own related studies, proposing that Reg proteins exhibit dimorphic effects. Results: The activity of Reg proteins is not as simplistic as previously perceived but shows auto-immunogenicity depending on different pathophysiological microenvironments. The immunogenicity of Reg proteins could recruit immune cells leading to an anti-tumor effect. Such functional diversity is correlated with their structural characteristics: the N-terminal region contributes to autoantigenicity, while the C-type lectin fragment near the C-terminal determines the trophic action. It should be noted that B-cell masking antigens might also reside within the C-type lectin domain. Conclusions: Reg proteins have dual functional roles under various physiological and pathological conditions. These theoretical foundations facilitate the subsequent development of diagnostic reagents and therapeutic drugs targeting Reg proteins. Full article

Type 1 diabetes mellitus is an autoimmune condition characterized by the destruction of pancreatic β-cells, necessitating insulin therapy to prevent life-threatening complications such as diabetic ketoacidosis. Despite advancements in glucose monitoring and pharmacological treatments, managing this disease remains challenging, often leading to long-term complications and psychological burdens, including diabetes distress. Advanced treatment options, such as whole-pancreas transplantation and islet transplantation, aim to restore insulin production and improve glucose control in selected patients with diabetes. The risk of transplant rejection necessitates immunosuppressive therapy, which increases susceptibility to infections and other adverse effects. Additionally, surgical complications, including infection and bleeding, are significant concerns, particularly for whole-pancreas transplantation. Recently, stem cell-derived therapies for type 1 diabetes have emerged as a promising alternative, offering potential solutions to overcome the limitations of formerly established transplantation methods. The purpose of this scoping review was to: (1) summarize the current evidence on achieved insulin independence following various transplantation methods of insulin-producing cells in patients with type 1 diabetes; (2) compare insulin independence rates among whole-pancreas transplantation, islet cell transplantation, and stem cell transplantation; and (3) identify limitations, challenges and potential future directions associated with these techniques. We systematically searched three databases (PubMed, Scopus, and Web of Science) from inception to November 2024, focusing on English-language, peer-reviewed clinical studies. The search terms used were ‘transplantation’ AND ‘type 1 diabetes’ AND ‘insulin independence’. Studies were included if they reported on achieved insulin independence, involved more than 10 patients with type 1 diabetes, and had a mean follow-up period of at least one year. Reviewers screened citations and extracted data on transplant type, study population size, follow-up duration, and insulin independence rates. We identified 1380 papers, and after removing duplicates, 705 papers remained for title and abstract screening. A total of 139 English-language papers were retrieved for full-text review, of which 48 studies were included in this review. The findings of this scoping review indicate a growing body of literature on transplantation therapy for type 1 diabetes. However, significant limitations and challenges, like insufficient rates of achieved insulin independence, risks related to immunosuppression, malignant diseases, and ethical issues remain with each of the established techniques, highlighting the need for innovative approaches such as stem cell-derived islet transplantation to promote β-cell regeneration and protection. Full article

Hypericum perforatum transformed shoot lines (TSL) regenerated from corresponding hairy roots and non-transformed shoots (NTS) were comparatively evaluated for their phenolic compound contents and in vitro inhibitory capacity against target enzymes (monoamine oxidase-A, cholinesterases, tyrosinase, α-amylase, α-glucosidase, lipase, and cholesterol esterase). Molecular docking was conducted to assess the contribution of dominant phenolic compounds to the enzyme-inhibitory properties of TSL samples. The TSL extracts represent a rich source of chlorogenic acid, epicatechin and procyanidins, quercetin aglycone and glycosides, anthocyanins, naphthodianthrones, acyl-phloroglucinols, and xanthones. Concerning in vitro bioactivity assays, TSL displayed significantly higher acetylcholinesterase, tyrosinase, α-amylase, pancreatic lipase, and cholesterol esterase inhibitory properties compared to NTS, implying their neuroprotective, antidiabetic, and antiobesity potential. The docking data revealed that pseudohypericin, hyperforin, cadensin G, epicatechin, and chlorogenic acid are superior inhibitors of selected enzymes, exhibiting the lowest binding energy of ligand–receptor complexes. Present data indicate that H. perforatum transformed shoots might be recognized as an excellent biotechnological system for producing phenolic compounds with multiple health benefits. Full article

Despite the effectiveness of insulin injections in managing hyperglycemia in type 1 diabetes mellitus (T1DM), they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential and prospects of emerging treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, pancreatic islet cell transplantation, and teplizumab. We review emerging treatment modalities for T1DM, highlighting several promising strategies with varied mechanisms and outcomes. Mesenchymal stem cells demonstrate potential in modulating the immune response and preserving or restoring beta-cell function, although variability in sources and administration routes necessitates further standardization. Similarly, MSC-derived exosomes show promise in promoting beta-cell regeneration and immune regulation, supported by early-stage studies showing improved glucose homeostasis in animal models, albeit with limited clinical data. Gene therapy, utilizing techniques like CRISPR-Cas9, offers targeted correction of genetic defects and immune modulation; however, challenges in precise delivery and ensuring long-term safety persist. Islet allotransplantation and pancreatic islet cell transplantation have achieved some success in restoring insulin independence, yet challenges such as donor scarcity and immunosuppression-related complications remain significant. Teplizumab, an anti-CD3 monoclonal antibody, has demonstrated potential in delaying T1DM onset by modulating immune responses and preserving beta-cell function, with clinical trials indicating prolonged insulin production capability. Despite significant progress, standardization, long-term efficacy, and safety continue to pose challenges across these modalities. Conclusion: While these therapies demonstrate significant potential, challenges persist. Future research should prioritize optimizing these treatments and validating them through extensive clinical trials to enhance T1DM management and improve patient outcomes. Full article

This study unveils verapamil’s compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil’s capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resilience. A pivotal revelation of our research is verapamil’s induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil’s efficacy in fostering β-cell recovery post-metronidazole infliction. Collectively, our findings advocate for verapamil’s reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell regeneration, thereby offering fresh avenues for diabetes management strategies aimed at preserving and augmenting β-cell functionality. Full article

Type 2 diabetes is characterized by hyperglycemia and a relative loss of β–cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin–nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α–amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA–IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of β–cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes. Full article

The golden rule in tissue engineering is the creation of a synthetic device that simulates the native tissue, thus leading to the proper restoration of its anatomical and functional integrity, avoiding the limitations related to approaches based on autografts and allografts. The emergence of synthetic biocompatible materials has led to the production of innovative scaffolds that, if combined with cells and/or bioactive molecules, can improve tissue regeneration. In the last decade, silk fibroin (SF) has gained attention as a promising biomaterial in regenerative medicine due to its enhanced bio/cytocompatibility, chemical stability, and mechanical properties. Moreover, the possibility to produce advanced medical tools such as films, fibers, hydrogels, 3D porous scaffolds, non-woven scaffolds, particles or composite materials from a raw aqueous solution emphasizes the versatility of SF. Such devices are capable of meeting the most diverse tissue needs; hence, they represent an innovative clinical solution for the treatment of bone/cartilage, the cardiovascular system, neural, skin, and pancreatic tissue regeneration, as well as for many other biomedical applications. The present narrative review encompasses topics such as (i) the most interesting features of SF-based biomaterials, bare SF’s biological nature and structural features, and comprehending the related chemo-physical properties and techniques used to produce the desired formulations of SF; (ii) the different applications of SF-based biomaterials and their related composite structures, discussing their biocompatibility and effectiveness in the medical field. Particularly, applications in regenerative medicine are also analyzed herein to highlight the different therapeutic strategies applied to various body sectors. Full article

Background: Diabetes mellitus (DM) is a non-communicable, life-threatening syndrome that is present all over the world. The use of eco-friendly, cost-effective, and green-synthesised nanoparticles as a medicinal therapy in the treatment of DM is an attractive option. Objective: In the present study, silver nanoparticles (AI-AgNPs) were biosynthesized through the green synthesis method using Azadirachta indica seed extract to evaluate their anti-diabetic potentials. Methods: These nanoparticles were characterized by using UV-visible spectroscopy, Fourier transform infrared spectrophotometers (FTIR), scanning electron microscopy (SEM), DLS, and X-ray diffraction (XRD). The biosynthesized AI-AgNPs and crude extracts of Azadirachta indica seeds were evaluated for anti-diabetic potentials using glucose adsorption assays, glucose uptake by yeast cells assays, and alpha-amylase inhibitory assays. Results: Al-AgNPs showed the highest activity (75 ± 1.528%), while crude extract showed (63 ± 2.5%) glucose uptake by yeast at 80 µg/mL. In the glucose adsorption assay, the highest activity of Al-AgNPs was 10.65 ± 1.58%, while crude extract showed 8.32 ± 0.258% at 30 mM, whereas in the alpha-amylase assay, Al-AgNPs exhibited the maximum activity of 73.85 ± 1.114% and crude extract 65.85 ± 2.101% at 100 µg/mL. The assay results of AI-AgNPs and crude showed substantial dose-dependent activities. Further, anti-diabetic potentials were also investigated in streptozotocin-induced diabetic mice. Mice were administered with AI-AgNPs (10 to 40 mg/kg b.w) for 30 days. Conclusions: The results showed a considerable drop in blood sugar levels, including pancreatic and liver cell regeneration, demonstrating that AI-AgNPs have strong anti-diabetic potential. Full article

Mobilization of CTCs after various types of therapy, such as radiation therapy, has been reported, but systematic study of CTCs after chemotherapy remained quite limited. In this study, we sequentially examined CTC numbers after single-dose and repetitive-dose chemotherapy, including FORFIRINOX (FFX) and Gemcitabine and nab-Paclitaxel (GnP) using two pancreatic cancer xenograft models. CTC was detected by the immunocytology-based microfluidic platform. We further examined the dynamic change in the histology of primary tumor tissues during chemotherapy. We confirmed a transient increase in CTCs 1–2 weeks after single-dose and repetitive-dose of FFX/GnP chemotherapy. Histological examination of the primary tumors revealed that the peak period of CTC at 1–2 weeks after chemotherapy corresponded to the maximal destructive phase consisting of cell cycle arrest, apoptosis of tumor cells, and blood vessel destruction without secondary reparative tissue reactions and regeneration of tumor cells. These findings indicate that mobilization of CTCs early after chemotherapy is mediated by the shedding of degenerated tumor cells into the disrupted blood vessels driven by the pure destructive histological changes in primary tumor tissues. These results suggest that sequential CTC monitoring during chemotherapy can be a useful liquid biopsy diagnostic tool to predict tumor chemosensitivity and resistance in preclinical and clinical settings. Full article

The scourge of type-1 diabetes (T1D) is the morbidity and mortality it and its complications cause at a younger age. This propels the constant search for better diagnostic, treatment, and management strategies, with the ultimate quest being a cure for T1D. Recently, the therapeutic potential of exosomes has generated a lot of interest. Among the characteristics of exosomes of particular interest are (a) their regenerative capacity, which depends on their “origin”, and (b) their “content”, which determines the cell communication and crosstalk they influence. Other functional capacities, including paracrine and endocrine homeostatic regulation, pathogenic response ability resulting in insulin secretory defects or β-cell death under normal metabolic conditions, immunomodulation, and promotion of regeneration, have also garnered significant interest. Exosome “specificity” makes them suitable as biomarkers or predictors, and their “mobility” and “content” lend credence to drug delivery and therapeutic suitability. This review aims to highlight the functional capacities of exosomes and their established as well as novel contributions at various pathways in the onset and progression of T1D. The pathogenesis of T1D involves a complex crosstalk between insulin-secreting pancreatic β-cells and immune cells, which is partially mediated by exosomes. We also examine the potential implications for type 2 diabetes (T2D), as the link in T2D has guided T1D exploration. The collective landscape presented is expected to help identify how a deeper understanding of exosomes (and their cargo) can provide a framework for actionable solutions to prevent, halt, or change the very course of T1D and its complications. Full article

The relationship between the type and intensities of lipids of blood and pancreas and the pathological changes in the pancreas during severe acute pancreatitis (SAP) remains unclear. In our study, we employed a rat model of SAP induced through intraperitoneal ornithine injections. We collected serum and pancreas samples at various time points (0–144 h) for histopathological and biochemical assessments, followed by lipidomic analyses using LC-MS/MS or in situ mass spectrometry imaging (MSI) To discern changes over time or at specific points, we employed time-course and univariate analyses for lipid screening, respectively. Our findings indicated that the peak inflammation in the Orn-SAP model occurred within the 24–30 h timeframe, with evident necrosis emerging from 24 h onwards, followed by regeneration starting at 48 h. Time-course analysis revealed an overall decrease in glycerophospholipids (PEs, PCs, LPEs, LPCs), while CEs exhibited an increase within the pancreas. Univariate analysis unveiled a significant reduction in serum TAGs containing 46–51 carbon atoms at 24 h, and CERs in the pancreas significantly increased at 30 h, compared with 0 h. Moreover, a substantial rise in TAGs containing 56–58 carbon atoms was observed at 144 h, both in serum and pancreas. MSI demonstrated the CERs containing saturated mono-acyl chains of 16 and 18 carbon atoms influenced pancreatic regeneration. Tracing the origin of FFAs hydrolyzed from pancreatic glycerophospholipids and serum TAGs during the early stages of inflammation, as well as FFAs utilized for CEs and CERs synthesis during the repair phase, may yield valuable strategies for diagnosing and managing SAP. Full article