Pancreatic Duct Cells Isolated From Canines Differentiate Into Beta-Like Pancreatic Islet Cells

In this study, we isolated and cultured pancreatic ductal cells from canines and revealed the possibility for using them to differentiate into functional pancreatic beta cells in vitro. Passaged pancreatic ductal cells were induced to differentiate into beta-like pancreatic islet cells using a mixture of induced factors. Differentiated pancreatic ductal cells were analyzed based on intracellular insulin granules using transmission electron microscopy, the expression of insulin and glucagon using immunofluorescence, and glucose-stimulated insulin secretion using ELISA. Our data revealed that differentiated pancreatic ductal cells not only expressed insulin and glucagon but also synthesized insulin granules and secreted insulin at different glucose concentrations. Our study might assist in the development of effective cell therapies for the treatment of type 1 diabetes mellitus in dogs.

Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine induced cell death

Pancreatic β-cells depend on the well-balanced regulation of cytosolic zinc concentrations, providing sufficient zinc ions for the processing and storage of insulin, but avoiding toxic effects. The zinc transporter ZnT8, encoded by SLC30A8, is a key player regarding islet cell zinc homeostasis, and polymorphisms in this gene are associated with altered type 2 diabetes susceptibility in man. The objective of this study was to investigate the role of ZnT8 and zinc in situations of cellular stress as hypoxia or inflammation. Isolated islets of wild-type and global ZnT8-/- mice were exposed to hypoxia or cytokines and cell death was measured. To explore the role of changing intracellular Zn2+ concentrations, wild-type islets were exposed to different zinc concentrations using zinc chloride or the zinc chelator N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN). Hypoxia or cytokine (TNFα, IFNγ, IL1β) treatment induced islet cell death, but to a lesser extent in islets from ZnT8-/- mice, which were shown to have a reduced zinc content. Similarly, chelation of zinc with TPEN reduced cell death in wild-type islets treated with hypoxia or cytokines, whereas increased zinc concentrations aggravated the effects of these stressors. This study demonstrates a reduced rate of cell death in islets from ZnT8-/- mice as compared to wild-type islets when exposed to two distinct cellular stressors, hypoxia or cytotoxic cytokines. This protection from cell death is, in part, mediated by a reduced zinc content in islet cells of ZnT8-/- mice. These findings may be relevant for altered diabetes burden in carriers of risk SLC30A8 alleles in man.

The Role of Mesenchymal Stem Cells in Regulating PDGF and VEGF during Pancreatic Islet Cells Regeneration in Diabetic Animal Model

Introduction: Diabetes is a heterogeneous group of metabolic diseases characterized by elevated blood glucose due to autoimmune disorder or a combination of insulin resistance and insulin deficiency. VEGF and PDGF are the main actors in the regeneration of damaged pancreatic tissue. However, the prolonged release of these molecules may induce fibrosis formation. Mesenchymal stem cells (MSCs) have a high potential to regenerate damaged pancreatic tissue by releasing PDGF and VEGF. Aim: This study aimed to investigate the effect of MSCs on the levels of PDGF and VEGF on days 2 and 44 in diabetic mice and determine the number of pancreatic islet cells and blood glucose levels. Materials and methods: This study used a post-control group design with animals divided into five groups: sham, control, and three treatment groups (P) which were given MSCs at doses of 1.5×105, 3×105, and 6×105 cells. The levels of PDGF, VEGF, and blood glucose were measured by enzyme-linked immunosorbent assay (ELISA), while the number of pancreatic islet cells was analyzed using H&E staining. Results: This study showed a significant increase of VEGF and PDGF levels on day 2 and a significant increase in islet cell percentages on day 44 in line with the decreased blood glucose level. However, there was no difference between VEGF and PDGF levels on day 44. Conclusions: MSCs regulate PDGF and VEGF levels in wound healing phases and remodel pancreatic islet β-cells regeneration to control blood glucose in diabetic model mice.

Effect of COVID-19 Infection in the Patients with Diabetes Mellitus

Background: Coronavirus is pandemic virus infection which has recently affected the globe, and as a result, in patients with non-communicable diseases, the associated morbidity and death are substantially greater. One of the most common non-communicable diseases linked to worsening clinical conditions in corona virus patients is diabetes mellitus (dm). Covid-19 is a zoonotic illness that was firstly found in wuhan city of china, and is now recognized a zoonotic disease that spreads from moist animals to people in 2019. The disease has a low fatality rate and only affects the most seriously ill patients. Approximately 80% of the cases involve patients who are seriously to moderately ill. Since the outbreak of the disease, the number of people who have died has continuously increased. Summary: The aim for this study is to determine the receptors involved in diabetes and the pathogenetic relationship btw. Covid-19 and diabetes. Both diseases are characterized by inflammation and the release of inflammatory markers. The roles of angiotensin-converting enzyme molecule and dipeptidyl peptidase in covid-19 and diabetes have been investigated. The effects of glucocorticoids and catecholamines, invasion of pancreatic islet cells, medications used to treat covid-19, and hence the lockdown policy, may have a deleterious impact on diabetes patients' glucose control. The results of covid-19 research involving diabetic and non-diabetic patients were also examined. Various medication trials, such as the dapagliflozin and linagliptin trials are still being conducted to see if certain medications are suitable for diabetic people with covid-19. Conclusion: Diabetes is a risk factor for covid-19 patients, according to the data, leading to their severity and mortality. This article also contains guidelines and recommendations that may be useful in the management and avoidance of diabetic individuals who are infected with covid-19.

Anti-hyperglycemic Efficiency of the Aqueous Seed Extract of Mucuna pruriens in Nicotinamide-Streptozotocin-induced Diabetic Wistar Rats

This study was undertaken to evaluate the remedial effect of the aqueous seed extract of Mucuna pruriens (ASEMP) on the endocrine region of pancreas of nicotinamide-streptozotocin-induced diabetes in Wistar rats. The anti-hyperglycemic efficiency of two varieties of Mucuna pruriens var utilis; IIHR Selection 3 and Arka Dhanvantari was investigated. Oral administration of ASEMP against the nicotinamide-streptozotocin-induced diabetes in the Wistar rats showed anti-hyperglycemic effect on the blood glucose level (94 ± 0.2 mg/dl ASEMP 400 mg/kg) when compared with the control group (92 ± 0.2 mg/dl glibenclamide 5 mg/kg), (248 ± 0.3 mg/dl Diabetic control) and (90 ± 0.3 mg/dl Normal control). Significant reduction in creatinine level of the nicotinamide-streptozotocin-induced diabetic rats treated with ASEMP was also recorded. Histopathology examination of the endocrine region of pancreas of the rats revealed restoration of pancreatic islet cells in the diabetic-ASEMP treated rats as the beta cell mass increased and necrotic changes was reduced significantly in contrast with the diabetic control group which showed degenerated pancreatic islet cells. Therefore, this study supports and recommends the exploration of the aqueous seed extract of M. pruriens as an alternative medicine for the management of type-2 diabetes.

Adult-onset Focal Nesidioblastosis with Nodular Formation Mimicking Insulinoma

Nesidioblastosis is defined as the neoformation of the islets of Langerhans from the pancreatic ductal epithelium and is recognized as the most common cause of hyperinsulinemic hypoglycemia in infants. We herein report an extremely rare case of adult-onset focal nesidioblastosis with the unusual feature of hyperplastic nodular formation. A 55-year-old woman was admitted to our hospital for a tumor detected in the body of the pancreas by magnetic resonance imaging screening. Laboratory examinations showed a high insulin level in the blood. Contrast-enhanced computed tomography and the selective arterial calcium injection test suggested the presence of multiple insulinomas in the body and tail of the pancreas, and, thus, the patient underwent distal pancreatectomy. A histopathological examination of the tumor in the body of the pancreas showed the nodular hyperplasia of islet-like cell clusters. In addition, many small intralobular ductules and islet cells appeared to be budding from the proliferating ductal epithelium, forming “ductuloinsular complexes”. No other abnormal lesion was detected in the remainder of the pancreas. The histopathological diagnosis was focal nesidioblastosis. The patient has remained free of the recurrence of hypoglycemic episodes for more than 31 months. The present case of rare adult-onset focal nesidioblastosis with hyperplastic nodular formation was preoperatively identified as an apparent pancreatic tumor mimicking insulinoma. Nesidioblastosis and insulinoma need to be considered in cases of hyperinsulinemic hypoglycemia, even in adult patients.

Research Progress on the Molecular Mechanism of EGCG3 ″ Me in the Treatment of Diabetes Based on Visual Sensor Images

Diabetes is a chronic metabolic disease with abnormal blood glucose and lipid metabolism caused by insufficient insulin secretion, which seriously affects human health. For solving the problem of treating diabetes, it is particularly important to observe the research progress of the molecular mechanism of EGCG3 ″ Me in the treatment of diabetes based on visual sensor images. This research has not been verified in practice, but many scientists are already studying it. This article is aimed at studying the molecular mechanism of using EGCG3 ″ Me to treat diabetes based on visual sensor images. This article introduces the concept and application of visual image sensor in detail, using a superpixel segmentation method to realize image observation. The EGCG3 ″ Me was extracted and used in diabetes treatment experiments. The experimental results showed that the blood glucose of the mice in the experimental group had returned to normal 60 minutes after the administration of glucose in the blank control group, and the blood glucose of the mice in the control group had basically returned to normal after 120 minutes. Compared with the model group, the number of acinar paging and the number of cells in the pancreatic islets increased in the mice after EGCG3 ″ Me treatment, indicating that EGCG3 ″ Me has the effect of protecting and repairing pancreatic islet cells.

Development of islet organoids from human induced pluripotent stem cells in a cross-linked collagen scaffold

Islets organoids would have value in the cell replacement therapy for diabetes apart from usual personalized drug screening routes. Generation of a large number of Islets like clusters, with ability to respond to glucose stimulation appears to be an ideal choice. In this study we have generated islet organoids with the ability to respond to glucose stimulation by insulin release. The source of the cells was an iPSC cell line differentiated into the pancreatic progenitors. These cells were assembled in matrigel or cross-linked collagen scaffold and compared for their efficacy to release insulin upon stimulation with glucose. The assembled organoids were examined by immunohistochemistry and expression of the relevant marker genes. The organoids showed expression of islet like markers in both - matrigel and crosslinked collagen scaffold. The islet organoids in both the cases showed release of insulin upon stimulation with glucose. The crosslinked collagen scaffold is quite stable and supports islet cells growth and function.

Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bi-transgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in β-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. The utility of this model is enhanced by the ability to form tumor-derived allografts. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

Increased expression of viral sensor MDA5 in pancreatic islets and in hormone-negative endocrine cells in recent onset type 1 diabetic donors

The interaction between genetic and environmental factors determines the development of type 1 diabetes (T1D). Some viruses are capable of infecting and damaging pancreatic β-cells, whose antiviral response could be modulated by specific viral RNA receptors and sensors such as Melanoma Differentiation Associated gene 5 (MDA5), encoded by the IFIH1 gene. MDA5 has been shown to be involved in pro-inflammatory and immunoregulatory outcomes, thus determining the response of pancreatic islets to viral infections. Although the function of MDA5 has been previously well explored, a detailed immunohistochemical characterization of MDA5 in pancreatic tissues of non-diabetic and T1D donors is still missing. In the present study we used multiplex immunofluorescence imaging analysis to characterize MDA5 expression and distribution in pancreatic tissues obtained from 22 organ donors (10 non-diabetic autoantibody-negative, 2 autoantibody-positive, 8 recent-onset and 2 long-standing T1D). In non-diabetic control donors, MDA5 was expressed both in α- and in β-cells. The colocalization rate imaging analysis showed that MDA5 was preferentially expressed in α-cells. In T1D donors, we observed an increased colocalization rate MDA5-glucagon respect to MDA5-insulin in comparison to non-diabetic controls; such increase was more pronounced in recent onset respect to long standing T1D donors. Of note, an increased colocalization rate MDA5-glucagon was found in insulin-deficient-islets (IDI) respect to insulin containing islets (ICI). Strikingly, in T1D donors we detected the presence of MDA5-positive/hormones-negative endocrine islet-like clusters, putatively deriving from dedifferentiation or neogenesis phoenomena. These clusters were exclusively identified in recent onset donors and not detected in autoantibody-positive non-diabetic or T1D long-standing ones. In conclusion, we showed that MDA5 is preferentially expressed in α-cells and its expression is increased in recent onset T1D donors. Finally, we observed that MDA5 may also characterize the phenotype of dedifferentiated or newly forming islet cells, thus opening to novel roles for MDA5 in pancreatic endocrine cells.