Islets Of Langerhans Research Articles

Evaluating maternal toxicity induced by aqueous extract of Bambusa vulgaris shoot through biochemical, hematological, and histopathological assessment in pregnant Wistar rats

Exposure to teratogenic agents during pregnancy can lead to fetal abnormalities. Establishing histological, hematological, and biochemical parameters is pivotal to enhancing the evaluation of the effect of any substance on embryo-fetal development. The present study investigated the maternal toxicity of aqueous extract of Bambusa vulgaris Schrad. ex J.C. Wendl shoots in pregnant Wistar rats. The pregnant rats were then allocated into four groups (n=6): a control group (without treatment) and three test groups (treated with the extract 250, 500, and 1000 mg/Kg, respectively). The treatment was initiated on gestational day (GD) 6 and continued until the 15th day. On GD 20, all the rats were anesthetized and subjected to laparotomy. Blood samples were collected from the pregnant rats for hematological and biochemical analyses, while various organs were isolated for histopathological studies. The study demonstrates dose-dependent toxicity of the extract, with significant variations (P<0.001) observed in ALP and AST levels at the 1000 mg/kg dose, suggesting hepatic impairment in maternal subjects. Moreover, significant variations in total leukocyte and lymphocyte counts suggested pronounced inflammation or multi-organ dysfunction at this dose. Histopathological examination also revealed various indicators of multi-organ failure, including transmural mixed inflammation in the gall bladder, disruption of cardiac myofibre arrangement, tubular cell damage in the kidneys, cellular alterations in the liver, shrinking of pancreatic Langerhans islets, and lymphoid depletion in the spleen at 1000 mg/kg dose. These findings underscore the potential maternal toxicity associated with Bambusa vulgaris shoots, highlighting its potential risk for consumption during pregnancy and emphasizing the need for further research and caution regarding its use during this critical period.

Emerging approaches for the development of artificial islets.

The islet of Langerhans, functioning as a "mini organ", plays a vital role in regulating endocrine activities due to its intricate structure. Dysfunction in these islets is closely associated with the development of diabetes mellitus (DM). To offer valuable insights for DM research and treatment, various approaches have been proposed to create artificial islets or islet organoids with high similarity to natural islets, under the collaborative effort of biologists, clinical physicians, and biomedical engineers. This review investigates the design and fabrication of artificial islets considering both biological and tissue engineering aspects. It begins by examining the natural structures and functions of native islets and proceeds to analyze the protocols for generating islets from stem cells. The review also outlines various techniques used in crafting artificial islets, with a specific focus on hydrogel-based ones. Additionally, it provides a concise overview of the materials and devices employed in the clinical applications of artificial islets. Throughout, the primary goal is to develop artificial islets, thereby bridging the realms of developmental biology, clinical medicine, and tissue engineering.

Isolation of feline islets of Langerhans by selective osmotic shock produces glucose responsive islets.

Pancreatic islet isolation is essential for studying islet physiology, pathology, and transplantation, and feline islets could be an important model for human type II diabetes mellitus (T2D). Traditional isolation methods utilizing collagenases inflict damage and, in cats, may contribute to the difficulty in generating functional islets, as demonstrated by glucose-stimulated insulin secretion (GSIS). GLUT2 expression in β cells may allow for adaptation to hyperosmolar glucose solutions while exocrine tissue is selectively disrupted. Here we developed a protocol for selective osmotic shock (SOS) for feline islet isolation and evaluated the effect of different hyperosmolar glucose concentrations (300 mmol/L and 600 mmol/L) and incubation times (20 min and 40 min) on purity, morphology, yield, and GSIS. Across protocol treatments, islet yield was moderate and morphology excellent. The treatment of 600 mmol/L glucose solution with 20 min incubation resulted in the highest stimulation index by GSIS. Glucose responsiveness was demonstrated, permitting future in vitro studies. This research opens avenues for understanding feline islet function and transplantation possibilities and enables an additional islet model for T2D.

Repositioning the Early Pathology of Type 1 Diabetes to the Extraislet Vasculature.

Type 1 diabetes (T1D) is a prototypic T cell-mediated autoimmune disease. Because the islets of Langerhans are insulated from blood vessels by a double basement membrane and lack detectable lymphatic drainage, interactions between endocrine and circulating T cells are not permitted. Thus, we hypothesized that initiation and progression of anti-islet immunity required islet neolymphangiogenesis to allow T cell access to the islet. Combining microscopy and single cell approaches, the timing of this phenomenon in mice was situated between 5 and 8 wk of age when activated anti-insulin CD4 T cells became detectable in peripheral blood while peri-islet pathology developed. This "peri-insulitis," dominated by CD4 T cells, respected the islet basement membrane and was limited on the outside by lymphatic endothelial cells that gave it the attributes of a tertiary lymphoid structure. As in most tissues, lymphangiogenesis seemed to be secondary to local segmental endothelial inflammation at the collecting postcapillary venule. In addition to classic markers of inflammation such as CD29, V-CAM, and NOS, MHC class II molecules were expressed by nonhematopoietic cells in the same location both in mouse and human islets. This CD45- MHC class II+ cell population was capable of spontaneously presenting islet Ags to CD4 T cells. Altogether, these observations favor an alternative model for the initiation of T1D, outside of the islet, in which a vascular-associated cell appears to be an important MHC class II-expressing and -presenting cell.

Influence of sphingolipid enzymes on blood glucose levels, development of diabetes, and involvement of pericytes.

Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis. Furthermore, we examined islet pericytes for sulfatide, and beta-cell receptors for GLP-1, both of which are related to the insulin production. We examined mRNA levels in islets from the DiViD and nPOD studies, performed genetic association analyses, and histologically investigated pericytes in the islets for sulfatide. Polymorphisms of the gene encoding the CERS6 enzyme responsible for synthesising dihydroceramide, a precursor to sulfatide, are associated with random blood glucose values in non-diabetic persons. This fits well with our finding of sulfatide in pericytes in the islets, which regulates the capillary blood flow in the islets of Langerhans, which is important for oxygen supply to insulin production. In the islets of newly diagnosed T1D patients, we observed low levels of GLP-1 receptors; this may explain the insulin resistance in their beta cells and their low insulin production. In T2D patients, we identified associated polymorphisms in both CERS2 and CERS6. Here, we describe several polymorphisms in sulfatide enzymes related to blood glucose levels and HbA1c in non-diabetic individuals. Islet pericytes from such persons contain sulfatide. Furthermore, low insulin secretion in newly diagnosed T1D may be explained by beta-cell insulin resistance due to low levels of GLP-1 receptors.

Histology and immunofluorescent study of the pancreas in lovebird (Agapornis personatus).

Lovebird (Agapornis personatus) is a monotypic species of bird of the lovebird genus in the parrot family Psittaculidae and order Psittaciformes. The present study was designed to investigate the histology and immunohistochemistry of the pancreas in the lovebird. Totally, three adult birds were used. The pancreas was assessed using histological and immunofluorescent staining to detect insulin, glucagon, somatostatin, pancreatic polypeptide (PP) and neuropeptide Y (NY). The exocrine pancreas was composed of pyramidal acinar cells with zymogen granules at the apical cytoplasm. The endocrine pancreas was identified as large alpha, small beta and mixed islets of Langerhans. No intercalated duct was observed. Alpha cells with a density of 28.55% were the most numerous cell type, which were populated throughout the large islets, especially at the periphery. The beta cells with a density of 15.78% were accumulated mostly at the periphery of islets. The delta cells exhibited 17.81% intensity. Despite their lower density, the distribution of delta cells was like that of A cells throughout the islets. PP and NY cells were distinguished with densities of 14.69% and 20.63%, respectively. Although the arrangement of acinar cells, ductal systems and endocrine islets reflects patterns observed in various avian species, the absence of intercalated duct, the presence of three types of Langerhans islets as alpha, beta and mixed islets and the high expression of NY in the islets were some unique features observed in the current study. These findings contribute to the broader understanding of avian pancreas histology.

HISTOPATHOLOGICAL PICTURE OF THE PANCREAS OF MICE (MUS MUSCULUS) DIABETES INDUCED BY STREPTOZOTOCIN-SUKROSA BY GIVING PEPAYA SEED EXTRACT (CARICA PAPAYA L.)

This study aimed to investigate the potential of papaya seed extract as an antihyperglycemic agent and to determine the histopathological features of the pancreas of female mice induced by streptozotocin-sucrose. The study used female DDY mice and divided them into five groups, including a negative control group, a positive control group, and three test groups given different doses of papaya seed methanol extract. The parameters measured were the decrease in fasting blood glucose levels, the number, diameter, and area of the islets of Langerhans in each group. The data was analyzed using the one-way ANOVA method with a confidence level of 95% followed by a comparison test using the Least Significant Difference method. The results showed that the methanol extract of papaya seeds has the potential to reduce blood glucose levels and improve the histological structure of the pancreas of diabetic mice induced by streptozotocin-sucrose at an optimum dose of 100 mg/kgBW. There was a significant difference in reducing blood glucose levels between the negative control group and the test group given 100 mg/kgBW papaya seed methanol extract after seven days of treatment. After fourteen days, there was a significant difference between the negative control group and test groups I, II, and III. Although no significant differences were found in the number, diameter, and area of the islets of Langerhans through morphometric photo testing, microscopic photo testing showed that test group I had the best histopathological picture with no vacuolization and necrosis found.

Regenerative medicine for diabetes: Unraveling the impact of stem cells

Diabetes poses a significant health challenge, particularly in developing nations, with an alarming annual increase in cases. Current medications mainly focus on managing hyperglycemia and preventing complications associated with diabetes. However, the article underscores the potential of stem cells in advancing diabetes treatment, particularly in the generation of insulin-producing β-cells. It highlights the damage to these cells within the islet of Langerhans in diabetic patients, whether through autoimmune reactions in type 1 diabetes or inherent changes affecting β-cell function in type 2 diabetes. The article suggests that cell replacement strategies, such as islet transplantation, could offer therapeutic options for diabetes. Stem cells, capable of differentiating into specialized cells, are presented as a promising avenue for creating insulin-producing β-cells, aiming to restore normal insulin levels and providing a more comprehensive and long-term solution compared to current medications. While the potential is promising, it's essential to note that stem cell therapies are still in the experimental stage, necessitating further research and clinical trials to establish their safety and efficacy for widespread use in diabetes treatment.

Efek Antidiabetes Kombinasi Ekstrak Mengkudu (Morinda citrifolia) dan Kunyit (Curcuma longa) pada Tikus yang dibuat Hiperglikemik

Background: Diabetes Mellitus is a disease characterized by hyperglycemia in a long time can cause the damage of pancreatic beta cells. Morinda citrifolia contains xeronine that can regenerate damaged pancreatic beta cells. While Curcuma longa contains curcumin which acts as an antioxidant will stabilize free radicals so it can inhibit pancreatic beta cell damage and stimulate insulin secretion.Methods: The study aim to analyze the effect of a combination of Morinda Citrifolia and Curcuma Longa in reducing blood glucose levels, increasing body weight and pancreatic histopathology in hyperglycemic mice. This type of research is an experiment with the Post Test Only Control Group. A total of 25 mice were divided into 5 groups namely PI (250 mg/dL), PII (500 mg/dL), PIII (750 mg/dL), K(+), and K(-). Blood glucose level was observed for 21 days followed by observation of pancreatic histopathology.Result: The results showed the percentage of glucose blood reduction occurred in the PI group (56.11%) and significantly different from negative controls (35.05%). There was no difference in body weight (p=0.7) and number of langerhans islet (p=0.360) in all treatment groups. The diameter of the Langerhans islet of the PI group (200.8 μm) was significantly different from the negative control (114.8 μm). (p&lt;0.05Conclusion : The combination of Morinda citrifolia and Curcuma longa extract can reduce blood glucose levels and increase body weight but not be able to optimally repair pancreatic islet damage.

Accuracy and Feasibility of Real-time Continuous Glucose Monitoring in Critically Ill Patients After Abdominal Surgery and Solid Organ Transplantation.

Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement has gained accuracy and reliability in outpatient and inpatient settings. The aim of this study was to assess the feasibility and accuracy of real-time continuous glucose monitoring (CGM) in ICU patients after major abdominal surgery. We included patients undergoing pancreatic surgery and solid organ transplantation (liver, pancreas, islets of Langerhans, kidney) requiring an ICU stay after surgery. We used a Dexcom G6 sensor, placed in the infraclavicular region, for real-time CGM. Arterial blood glucose measured by the amperometric principle (ABL 800; Radiometer, Copenhagen, Denmark) served as a reference value and for calibration. Blood glucose was also routinely monitored by a StatStrip bedside glucose meter. Sensor accuracy was assessed by mean absolute relative difference (MARD), bias, modified Bland-Altman plot, and surveillance error grid for paired samples of glucose values from CGM and acid-base analyzer (ABL). We analyzed data from 61 patients and obtained 1,546 paired glucose values from CGM and ABL. Active sensor use was 95.1%. MARD was 9.4%, relative bias was 1.4%, and 92.8% of values fell in zone A, 6.1% fell in zone B, and 1.2% fell in zone C of the surveillance error grid. Median time in range was 78%, with minimum (<1%) time spent in hypoglycemia. StatStrip glucose meter MARD compared with ABL was 5.8%. Our study shows clinically applicable accuracy and reliability of Dexcom G6 CGM in postoperative ICU patients and a feasible alternative sensor placement site.

Antidiabetic Activity of Ethanol-Water Fraction of Longjack Root (Eurycoma longifolia Jack.) in Streptozotocin-Nicotinamide Induced Rats

This study aims to determine the decrease in glucose levels, MDA levels, and histopathological appearance of the pancreatic organs of Wistar white rats after administration of the ethanol-water fraction of longjack root. This study used a completely randomized design with four treatment groups and six replications. The treatment consisted of normal control, negative control (Na-CMC 0.5% 5 ml/200 g body weight), positive control (glibenclamide 0.09 mg/200 g body weight), and treatment of the ethanol-water fraction of longjack root with a dose of 500 mg/kg body weight. The results showed that the ethanol-water fraction of longjack root at a dose of 500 mg/kg body weight had antidiabetic activity comparable to that of glibenclamide at a dose of 0.09/200 g body weight, namely blood glucose levels and MDA levels in white rats of 123.55 mg/dl and 2.83 nmol/ml. The results of histopathological analysis of the pancreas of white rats showed that administration of the ethanol-water fraction of longjack root could repair damage to the islets of Langerhans due to the administration of streptozotocin-nicotinamide.

Ectopic pancreatic adenocarcinoma in Meckel’s diverticulum: a case report

BackgroundMalignant neoplasms arising from Meckel’s diverticulum are rare and an adenocarcinoma in Meckel’s diverticulum originating from ectopic pancreatic tissue is even rarer. Herein, we report a patient with an ectopic pancreatic adenocarcinoma in Meckel’s diverticulum who was successfully treated with surgery and chemotherapy.Case presentationA woman in her sixties presented to another hospital with abdominal pain. Plain computed tomography suggested an abdominal tumor and she was referred to our hospital. Enhanced computed tomography revealed a 23-mm low-density tumor in the abdominal cavity. Surgery was performed with a tentative diagnosis of a mesenteric tumor, such as a gastrointestinal stromal tumor, schwannoma, or lymphoma. First, we inspected the peritoneal cavity with a laparoscope. This revealed numerous nodules in the small bowel mesentery, suggesting peritoneal dissemination. A 20-mm-diameter white tumor was found in the small intestine and diagnosed as a small intestinal cancer. The small intestine was partially resected laparoscopically through a small skin incision. The patient’s postoperative course was uneventful, and she was discharged on postoperative day 9. Pathological examination revealed well-differentiated adenocarcinoma in the small intestine. The tumor had developed from a sac-like portion protruding toward the serosal side and had a glandular structure lined with flattened atypical cells. Neither pancreatic acinar cells nor islets of Langerhans were evident, suggesting a Heinrich type 3 ectopic pancreas. The final diagnosis was an adenocarcinoma originating from an ectopic pancreas in Meckel’s diverticulum. After a smooth recovery, the patient commenced chemotherapy for pancreatic cancer.ConclusionsWe present a very rare case of ectopic pancreatic carcinoma in Meckel’s diverticulum.

CD4+ T Cells From Individuals With Type 1 Diabetes Respond to a Novel Class of Deamidated Peptides Formed in Pancreatic Islets.

The β-cell plays a crucial role in the pathogenesis of type 1 diabetes, in part through the posttranslational modification of self-proteins by biochemical processes such as deamidation. These neoantigens are potential triggers for breaking immune tolerance. We report the detection by LC-MS/MS of 16 novel Gln and 27 novel Asn deamidations in 14 disease-related proteins within inflammatory cytokine-stressed human islets of Langerhans. T-cell clones responsive against one Gln and three Asn deamidated peptides could be isolated from peripheral blood of individuals with type 1 diabetes. Ex vivo HLA class II tetramer staining detected higher T-cell frequencies in individuals with the disease compared to control individuals. Furthermore, there was a positive correlation between the frequencies of T cells specific for deamidated peptides, insulin antibody levels at diagnosis, and duration of disease. These results highlight that stressed human islets are prone to enzymatic and biochemical deamidation and suggest that both Gln and Asn deamidated peptides can promote the activation and expansion of autoreactive CD4+ T cells. These findings add to the growing evidence that post-translational modifications undermine tolerance and may open the road for the development of new diagnostic and therapeutic applications for individuals living with type 1 diabetes.

The impact of apelin-13 on cisplatin-induced endocrine pancreas damage in rats: an in vivo study.

Apelin-13 is a peptide hormone that regulates pancreatic endocrine functions, and its benefits on the endocrine pancreas are of interest. This study aims to investigate the potential protective effects of apelin-13 in cisplatin-induced endocrine pancreatic damage. Twenty-four rats were divided into four groups: control, apelin-13, cisplatin, and cisplatin + apelin-13. Caspase-3, TUNEL, and Ki-67 immunohistochemical staining were used as markers of apoptosis and mitosis. NF-κB/p65 and TNFα were used to show inflammation. β-cells and α-cells were also evaluated with insulin and glucagon staining in the microscopic examination. Pancreatic tissue was subjected to biochemical analyses of glutathione (GSH) and malondialdehyde (MDA). Apelin-13 ameliorated cisplatin-induced damage in the islets of Langerhans. The immunopositivity of apelin-13 on β-cells and α-cells was found to be increased compared to the cisplatin group (p = 0.001, p = 0.001). Mitosis and apoptosis were significantly higher in the cisplatin group (p = 0.001). Apelin-13 reduced TNFα, NF-κB/p65 positivity, and apoptosis caused by cisplatin (p = 0.001, p = 0.001, p = 0.001). While cisplatin caused a significant increase in MDA levels (p = 0.001), apelin caused a significant decrease in MDA levels (p = 0.001). The results demonstrated a significant decrease in pancreatic tissue GSH levels following cisplatin treatment (p = 0.001). Nevertheless, apelin-13 significantly enhanced cisplatin-induced GSH reduction (p = 0.001). On the other hand, the serum glucose level, which was measured as 18.7 ± 2.5mmol/L in the cisplatin group, decreased to 13.8 ± 0.7mmol/L in the cisplatin + apelin-13 group (p = 0.001). The study shows that apelin-13 ameliorated cisplatin-induced endocrine pancreas damage by reducing oxidative stress and preventing apoptosis.

Comprehensive Review on Pancreatic Head Cancer: Pathogenesis, Diagnosis, and Treatment Challenges in the Quest for Improved Survival.

This comprehensive review explores the complexities surrounding pancreatic head cancer, a highly fatal and challenging-to-treat illness with a survival rate of less than five years. Despite being a major contributor to cancer-related deaths, pancreatic head malignancy often eludes early detection due to its posterior location and high metastatic potential. The review delves into the associated symptoms, including gastric outlet obstruction and obstructive jaundice, highlighting the impact on the patient's eligibility for surgery. Examining recent advancements, the article discusses fast-track surgery recovery programs and emerging immunotherapeutic approaches, acknowledging the unique challenges posed by the immunosuppressive environment of pancreatic head cancer. Additionally, the review elucidates the intricate relationship between pancreatic cancer and glucose levels, emphasizing the role of islets of Langerhans in insulin production. The pathogenesis section explores lifestyle and genetic factors contributing to pancreatic head carcinoma, shedding light on risk factors such as smoking, obesity, diabetes, and hereditary predispositions. The extensive analysis of pancreatic cancer diagnosis methods encompasses imaging techniques, biopsies, and biomarkers, emphasizing the challenges posed by late-stage diagnoses. Addressing treatment modalities, the review emphasizes the significance of surgery, chemotherapy, radiotherapy, and targeted therapy. The intricate details of neoadjuvant, immunotherapy, and microbial therapy provide a comprehensive understanding of evolving treatment strategies. The review concludes by highlighting promising areas of research, including oncolytic viral therapy and gene editing technology, aiming to enhance the limited treatment options for this devastating disease.

New Fluorescent Dye for the Detection of Zn2+ in Living Cells and Fixed Sections of the Rat Pancreas.

We report the synthesis and characterization of a new 4-methoxyphenyl-2,2'-bipyridine-based ligand, such as 12, bearing dipicolylaminomethyl core as a receptor unit, as a probe for the fluorescence "turn-on" detection of Zn2+. Thus, in the presence of Zn2+ the probe 12 exhibited a fluorescence enhancement with a Stokes shift of ~ 180nm and photoluminescence quantum yields value of ~ 1.0. In addition, 12 exhibited higher binding constant for Zn2+ (~ 2 × 105M-1) with the LOD reaching the nanomolar level (~ 0.1 × 10-9M) compare to the previously reported probe 1. The stoichiometry and structure of the [Zn(12)]2+ and [Zn(1)]2+ complexes were supported by XRD analysis, DFT calculations and 1H NMR experiments. It was postulated that, as a result of binding of Zn2+, the sample exhibited a bright "on" state via the PET-ICT processes. Molecular docking studies and confocal fluorescence microscopy experiments demonstrated that the probe 12 could be used for the fluorescence detection of Zn2+ not only in artificially enriched with zinc salts live cells, but also in fixed tissues with cations are in a bound state. The high binding constant of compound 12 to Zn2+ cation allows it to be used for the accurate localization of pancreatic beta cells (islets of Langerhans).

On Chip Sorting of Stem Cell-Derived β Cell Clusters Using Traveling Surface Acoustic Waves.

There is a critical need for sorting complex materials, such as pancreatic islets of Langerhans, exocrine acinar tissues, and embryoid bodies. These materials are cell clusters, which have highly heterogeneous physical properties (such as size, shape, morphology, and deformability). Selecting such materials on the basis of specific properties can improve clinical outcomes and help advance biomedical research. In this work, we focused on sorting one such complex material, human stem cell-derived β cell clusters (SC-β cell clusters), by size. For this purpose, we developed a microfluidic device in which an image detection system was coupled to an actuation mechanism based on traveling surface acoustic waves (TSAWs). SC-β cell clusters of varying size (∼100-500 μm in diameter) were passed through the sorting device. Inside the device, the size of each cluster was estimated from their bright-field images. After size identification, larger clusters, relative to the cutoff size for separation, were selectively actuated using TSAW pulses. As a result of this selective actuation, smaller and larger clusters exited the device from different outlets. At the current sample dilutions, the experimental sorting efficiency ranged between 78% and 90% for a separation cutoff size of 250 μm, yielding sorting throughputs of up to 0.2 SC-β cell clusters/s using our proof-of-concept design. The biocompatibility of this sorting technique was also established, as no difference in SC-β cell cluster viability due to TSAW pulse usage was found. We conclude the proof-of-concept sorting work by discussing a few ways to optimize sorting of SC-β cell clusters for potentially higher sorting efficiency and throughput. This sorting technique can potentially help in achieving a better distribution of islets for clinical islet transplantation (a potential cure for type 1 diabetes). Additionally, the use of this technique for sorting islets can help in characterizing islet biophysical properties by size and selecting suitable islets for improved islet cryopreservation.

The Effects Of Simvastatin On Islets Of Langerhans In The Pancreas Of Rats: A Histological And Biochemical Study

Objective: This study explored the effect of simvastatin on the histomorphology of islets of Langerhans, glucose and insulin levels in rats. Study Design: The study was a one-year laboratory-based experimental control trial. Place and duration of study: It was conducted at Army Medical College Rawalpindi, in collaboration with the National Institute of Health Islamabad and Armed Force Institute of Pathology Rawalpindi. Methods: A one-year, laboratory-based, two-group experimental control trial was conducted. Thirty rats were assigned to each group: a control group receiving saline injections, and a simvastatin group receiving a simvastatin 60 mg/kg/day. Histological analysis of pancreatic islets, and measurements of blood glucose and insulin levels were performed. Statistical analysis was conducted using independent sample t-tests, with significance set at p &lt; 0.005. Results: While simvastatin treatment did not affect the number of islets of Langerhans, The area of pancreatic islets of Langerhans was significantly higher in the simvastatin treatment group compared to control (52,664±38,871 μm2 vs 24,643±16,256 μm2, p=0.001). Serum insulin levels were also significantly elevated with simvastatin treatment (21.49±7.03 μIU/ml) compared to control (16.72±5.38 μIU/ml) (p=0.005). There were no significant differences in weekly fasting blood glucose levels at 4 or 12 weeks between groups (p&gt;0.05). These findings suggest potential modulation of pancreatic islet function by simvastatin without affecting glycemic control in this model. Conclusions: These findings demonstrate that simvastatin treatment significantly impacts the morphology and function of pancreatic islets in rats, increasing insulin secretion without affecting blood glucose levels. Further research is necessary to elucidate the underlying mechanisms and clinical implications of these observations. Keywords: Simvastatin, islets of Langerhans, Sprague-Dawley rats, insulin, glucose, pancreas.

Phytochemicals profiling, in vitro and in vivo antidiabetic activity, and in silico studies on Ajuga iva (L.) Schreb.: A comprehensive approach

Abstract Ajuga iva (L.) Schreb. is a well-known antidiabetic medicinal plant used for several traditional medicine aspects in different areas of the world, including Libya. This study includes phytochemical analysis, antidiabetic evaluation, and in silico studies of the plant, A. iva, growing in Libya. The constituents of the plant were profiled using LC-MS/MS-QTOF analysis, and a total of 28 compounds were tentatively identified, including engeletin, pyrocatechol, eriodyctiol-7-hexoside, and 3,4-dihydroxybenzaldehyde, as major constituents. In addition, the steroidal compounds, i.e., 20-hydroxyecdysone, 24-dehydroprecyasterone, makisterone A, and ajugasterone D, which are considered chemomarkers for the plant, were also annotated by LC-MS analysis. The plant extract induced inhibition of α-amylase and α-glucosidase enzymes at IC50 values of 0.18 and 0.12 mg/mL, compared to the IC50 of the standard acarbose at 0.11 and 0.09 mg/mL, respectively. Fasting blood glucose (FBG, 360.7 mg/dL) levels were significantly reduced by the treatment of streptozotocin (STZ)-diabetic animals with 400 mg/kg (140.5 mg/dl) and 500 mg/kg (112.3 mg/dL) doses of the plant extract. The plant extract also induced a significant (p &lt; 0.01) increase in insulin serum level compared to the untreated diabetic rats; however, the higher dose of the plant induced similar insulin induction compared to glibenclamide. Histopathological examination of the pancreatic and liver tissues indicated that A. iva extract induced regeneration in the islets of Langerhans and liver cells compared to the untreated diabetic rats. Docking analysis demonstrated that eriodyctiol-7-hexoside, echinacoside, and 2″-galloylhyperin showed the lowest binding energies to the target sites of α-amylase and α-glucosidase enzymes, indicating their potential role in A. iva antidiabetic bioactivities. The results support the recorded traditional bioactivity of A. iva as an antidiabetic herb, whereas its contents of polyphenols play a major role in the plant’s antidiabetic effect.

High-Density Lipoprotein Is Located Alongside Insulin in the Islets of Langerhans of Normal and Rodent Models of Diabetes.

Recent studies have implicated pre-beta and beta lipoproteins (VLDL and LDL) in the etiopathogenesis of complications of diabetes mellitus (DM). In contrast, alpha lipoprotein (HDL) is protective of the beta cells of the pancreas. This study examined the distribution of HDL in the islets of Langerhans of murine models of type 1 diabetic rats (streptozotocin (STZ)-induced DM in Wistar rats) and type 2 models of DM rats (Goto-Kakizaki (GK), non-diabetic Zucker lean (ZL), and Zucker diabetic and fatty (ZDF)). The extent by which HDL co-localizes with insulin or glucagon in the islets of the pancreas was also investigated. Pancreatic tissues of Wistar non-diabetic, diabetic Wistar, GK, ZL, and ZDF rats were processed for immunohistochemistry. Pancreatic samples of GK rats fed with either a low-fat or a high-fat diet were prepared for transmission immune-electron microscopy (TIEM) to establish the cytoplasmic localization of HDL in islet cells. HDL was detected in the core and periphery of pancreatic islets of Wistar non-diabetic and diabetic, GK, ZL, and ZDF rats. The average total of islet cells immune positive for HDL was markedly (<0.05) reduced in GK and ZDF rats in comparison to Wistar controls. The number of islet cells containing HDL was also remarkably (p < 0.05) reduced in Wistar diabetic rats and GK models fed on high-fat food. The co-localization study using immunofluorescence and TIEM techniques showed that HDL is detected alongside insulin within the secretory granules of β-cells. HDL did not co-localize with glucagon. This observation implies that HDL may contribute to the metabolism of insulin.