Islet Damage Research Articles

Extraction, phytochemicals characterization, in vivo and in vitro anti-diabetic ability of non-extractable polyphenols from Undaria pinnatifida

Undaria pinnatifida (Up) is an edible seaweed known for its abundant nutrients and active compounds. In this research, six different methods, including acid hydrolysis extraction (AHE), alkaline hydrolysis extraction (LHE), enzymatic hydrolysis extraction (EHE), as well as their combinations with ultrasonic assisted extraction (AHE-U, LHE-U, EHE-U), were applied to extract non-extractable polyphenols from Up (UNEPPs). Results revealed that LHE-U was the most effective way to extract UNEPPs, it gave the highest yield (1.26 %) and total phenolics content (29.88 μg GAE/mg E), as well as considerable antioxidant and in vitro hypoglycemic effects. HPLC-Q-TOF-MS/MS analysis revealed the identification of 36 compounds from ULNEPPs, ferulic acid, p-coumaric acid and ferulic acid 4-O-glucuronide were the major compounds. In vivo study found that ULNEPPs could reduce fasting blood glucose (FBG) level, ameliorate abnormal glucose metabolism and dyslipidemia, repair insulin resistance and pancreas islet damage in type 2 diabetes (T2D) mice. Additionally, RT-qPCR analysis revealed that ULNEPPs improved glucose metabolism through the up-regulation of gene expression levels of Pi3k, Glut4, Akt, Ampk and the down-regulation of gene expression levels of Foxo1, Pgc-1α, Gsk-3β, Glut4, and G6pc. These results evidence that has the potential as dietary ingredients for preventing and treating T2D.

Exploring Novel Treatment Modalities for Type 1 Diabetes Mellitus: Potential and Prospects.

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.

Hypoglycemic Ability of Sericin-Derived Oligopeptides (SDOs) from Bombyx mori Yellow Silk Cocoons and Their Physiological Effects on Streptozotocin (STZ)-Induced Diabetic Rats.

Patients with diabetes require daily medication to maintain blood sugar levels. Nevertheless, the long-term use of antidiabetics can lose efficacy and cause degeneration in some patients. For long-term diabetes care, integrating natural dietary foods and medicine is being considered. This study investigated the impact of SDOs on blood sugar levels and their physiological effects on diabetic rats. We induced diabetes in male Wistar rats with STZ (50 mg/kg) and then administered an oral glucose tolerance test to determine the SDO dosage comparable to glibenclamide. The rats were divided into nine groups: normal, diabetic, and diabetic with insulin (10 U/kg), glibenclamide (0.6 mg/kg), bovine serum albumin (BSA; 200 mg/kg), soy protein isolate (200 mg/kg), or SDOs (50, 100, and 200 mg/kg). Diabetic rats administered SDOs had a higher body weight and serum insulin but a lower blood sugar than diabetic control rats. Biochemical assays indicated lower AST/SGOT, ALT/SGPT, BUN, and triglycerides but higher HDL in the SDO groups. Immunohistochemistry showed that SDOs reduced damaged islet cells, increased beta-cell size, and improved insulin levels while decreasing alpha cell size and glucagon. The vascular effects of SDOs were like those of normal control treatment and insulin treatment in diabetic rats. SDOs, a yellow silk protein, show potential for long-term diabetes care.

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<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.

Inhibition of Toll-like Receptor 4 Using Small Molecule, TAK-242, Protects Islets from Innate Immune Responses.

Islet transplantation is a therapeutic option to replace β-cell mass lost during type 1 or type 3c diabetes. Innate immune responses, particularly the instant blood-mediated inflammatory reaction and activation of monocytes, play a major role in the loss of transplanted islet tissue. In this study, we aimed to investigate the inhibition of toll-like receptor 4 (TLR4) on innate inflammatory responses. We first demonstrate a significant loss of graft function shortly after transplant through the assessment of miR-375 and miR-200c in plasma as biomarkers. Using in vitro models, we investigate how targeting TLR4 mitigates islet damage and immune cell activation during the peritransplant period. The results of this study support the application of TAK-242 as a therapeutic agent to reduce inflammatory and innate immune responses to islets immediately following transplantation into the hepatic portal vein. Therefore, TLR4 may serve as a target to improve islet transplant outcomes in the future.

Phytochemical composition of Tibetan tea fermented by Eurotium cristatum and its effects on type 1 diabetes mice and gut microbiota

“Golden-flower” Tibetan tea (GTT) is an innovative dark tea fermented via fungus Eurotium cristatum. To study GTT effects on alleviating the symptoms of type 1 diabetes mellitus (T1DM), GTT's extract (GTTE) was prepared. GTTE chemical compositions were analyzed via HPLC, pyrolysis-gas chromatography-mass (Py-GC-MS) spectrometry analysis, and chemistry analyses. GTTE effects on T1DM were explored on T1DM mice model induced by streptozotocin (STZ). GTTE was composed mainly of tea pigment theabrownin (TB) (49.18%), with high percentages of polysaccharide (16.93%), protein (10.15%), polyphenols (13.90%), amino acids (5.89%), caffeine (1.83%), and flavonoids (0.67%). Py-GC-MS results exhibited that GTTE constituted of phenols, lipids, sugars, and proteins. GTTE attenuated T1DM conditions of mice, relieved their liver and pancreatic injury, restored damaged islet cells, decreased oxidative stress by increasing superoxide dismutase (SOD) and catalase (CAT) levels, modulated cytokine expression leading to the decreasing pro-inflammatory cytokines TNF-α and IL-6, increased anti-inflammatory cytokines IL-4 to improve inflammatory responses, and optimized gut microbiota composition and structure based on high-throughput 16S rDNA sequencing, suggesting multi-channel anti-diabetes mechanisms.

Modulation of the gut microbiota alleviates insulin resistance in type 2 diabetic mice by daucosterol from Eleocharis dulcis peel

Daucosterol, a natural saponin from Eleocharis dulcis peel, exhibited anti-hyperglycemic properties. This study investigated daucosterol's effects on glycemic control, insulin resistance, and gut microbiota in type 2 diabetic mice. The results demonstrated that daucosterol treatment reduced fasting glucose, improved glucose intolerance and pancreatic islet damage. It decreased HOMA-IR and increased ISI, indicating enhanced insulin sensitivity. Daucosterol supplementation enriched gut microbiota diversity, including reducing Firmicutes and Desulfobacterota while increasing Bacteroidia. This involved an increase in Enterococcus, Akkermansia, Alistipes, Clostridium_sensu_stricto_1, and Odoribacter, coupled with decreased Aerococcus, Desulfovibrio, and Blautia, improved gut health. Uncultured_bacterium_g_Clostridium_sensu_stricto_1 and Bifidobacterium_pseudolongum were identified as major biomarkers. PICRUSt analysis revealed daucosterol improved the pathways of glycan biosynthesis and metabolism, lipid metabolism, carbohydrate metabolism, and some organismal systems. Therefore, daucosterol act as a potential anti-hyperglycemic agent, improving insulin resistance and optimizing gut microbiota to alleviate type 2 diabetes.

Impact of stress hyperglycemia on long-term prognosis in acute pancreatitis without diabetes.

Stress hyperglycemia has been confirmed as a strong predictor of poor short-term prognosis in acute pancreatitis. However, whether stress hyperglycemia affects the long-term prognosis of patients with acute pancreatitis is unclear. We aimed to investigate the effect of stress hyperglycemia on the long-term prognosis of non-diabetic patients with acute pancreatitis. This retrospective observational study was conducted on 4055 patients with acute pancreatitis from 1 January 2016 to 31 October 2020. The association between stress hyperglycemia and the prognosis was evaluated using regression modeling. There were 935(71.5%) normoglycemic and 373(28.5%) stress hyperglycemia patients. 46(12.3%) patients with stress hyperglycemia had evidence of diabetes compared with 33(3.5%) patients without stress hyperglycemia (P < 0.001). After multivariate adjustment, patients with stress hyperglycemia were more likely to have evidence of diabetes (OR 2.905, 95% CI 1.688-4.999) compared with normoglycemic. However, stress hyperglycemia is not associated with the recurrence of pancreatitis and progression to chronic pancreatitis. Stress hyperglycemia was independently associated with diabetes secondary to acute pancreatitis. Accordingly, a follow-up diabetes-screening program for AP with stress hyperglycemia is an important part of identifying the disease as soon as possible, delaying islet damage, and improving the prognosis of post-acute pancreatitis diabetes mellitus.

Immunomodulation of streptozotocin induced Type 1 diabetes mellitus in mouse model by Macrophage migration inhibitory factor-2 (MIF-2) homologue of human lymphatic filarial parasite, Wuchereria bancrofti

Helminth parasites modulate the host immune system to ensure a long-lasting asymptomatic form of infection generally, mediated by the secretion of immunomodulatory molecules and one such molecule is a homologue of human host cytokine, Macrophage migratory Inhibitory Factor (hMIF). In this study, we sought to understand the role of homologue of hMIF from the lymphatic filarial parasite, Wuchereria bancrofti (Wba-MIF2), in the immunomodulation of the Streptozotocin (STZ)-induced Type1 Diabetes Mellitus (T1DM) animal model. Full-length recombinant Wba-MIF2 was expressed and found to have both oxidoreductase and tautomerase activities. Wba-MIF2 recombinant protein was treated to STZ induced T1DM animals, and after 5 weeks pro-inflammatory (IL-1, IL-2, IL-6, TNF-α, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and gene expressions were determined in sera samples and spleen respectively. Pro-inflammatory and anti-inflammatory cytokine levels were significantly (p<0.05) up-regulated and down-regulated respectively, in the STZ-T1DM animals, as compared to treated groups. Histopathology showed macrophage infiltration and greater damage of islets of beta cells in the pancreatic tissue of STZ-T1DM animals, than Wba-MIF2 treated STZ-T1DM animals. The present study clearly showed the potential of Wba-MIF2 as an immunomodulatory molecule, which could modulate the host immune system in the STZ-T1DM mice model from a pro-inflammatory to anti-inflammatory milieu.

Polychlorinated biphenyls exposure and type 2 diabetes: Molecular mechanism that causes insulin resistance and islet damage.

Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that have been associated with type 2 diabetes (T2DM) in cohort studies. This review aims to comprehensively assess the molecular mechanisms of PCBs-induced T2DM. Recent progress has been made in the research of PCBs in liver tissue, adipose tissue, and other tissues. By influencing the function of nuclear receptors, such as the aryl hydrocarbon receptor (AhR), pregnancy X receptor (PXR), and peroxisome proliferator activated receptor γ (PPARγ), as well as the inflammatory response, PCBs disrupt the balance of hepatic glucose and lipid metabolism. This is associated with insulin resistance (IR) in the target organ of insulin. Through androgen receptor (AR), estrogen receptor α/β (ERα/β), and pancreato-duodenal-homeobox gene-1 (PDX-1), PCBs affect the secretion of insulin and increase blood glucose. Thus, this review is a discussion on the relationship between PCBs exposure and the pathogenesis of T2DM. It is hoped to provide basic concepts for diabetes research and disease treatment.

Study on the signaling pathways involved in the anti-hyperglycemic effect of raspberry ketone on zebrafish using integrative transcriptome and metabolome analyses.

Hyperglycemia leads to increased oxidative stress in mitochondria, an abnormal activation of intracellular inflammatory signals, and mediate multiple dysfunctions. Raspberry ketone (RK) is an aromatic phenolic compound found in many plants and could contribute to weight loss, restore impaired glucose tolerance, and has antioxidant properties. In our investigation, RK could greatly prevent islet, brain and other tissue damage caused by hyperglycemia in a zebrafish model with streptozotocin (STZ)-induced hyperglycemia. Body weight, insulin level, and food intake indexes were also restored by RK. Using transcriptome profiling, we found that RK administration could significantly attenuate STZ-induced insulin synthesis and pancreatic secretion as well as alter protein and carbohydrate metabolism. Metabolomics analysis results showed that RK could also prevent STZ-induced metabolic disorders, such as adenosine and sphingolipid metabolism. Integrative analysis of metabolome and transcriptome data and qRT-PCR validation of key metabolic regulatory genes (glut1, glut2, ctrb1, ccka, gck, pklr) confirmed that the purine pathway was the most enriched metabolic pathway, in which both metabolite accumulation and gene expression levels showed consistent change patterns upon RK treatment. Our study provides a new perspective for understanding the hypoglycemic mechanism of RK and may be helpful for investigating the modes of action of hypoglycemic drugs using the zebrafish hyperglycemia model.

A new labdane diterpenoid from Scoparia dulcis improving pancreatic function against islets cell apoptotic by Bax/Bcl-2/Caspase-3 pathway

Ethnopharmacological relevanceScoparia dulcis has been identified as a significant ethnopharmacological substance in the Li, Zhuang, and Dai ethnic groups of China. Traditional medicine use S. dulcis to treat numerous illnesses, most notably diabetes. The considerable antidiabetic properties of this herbal remedy have been established by several clinical investigations and animal experiments. The islet is the intended target of S. dulcis, although the cause of its activity and mechanism for diabetes treatment is unclear. The diterpenoids from S. dulcis have been shown in the literature to have significant hypoglycemic efficacy and to protect islet cells in vitro. Diterpenoids may be the components of this herbal remedy that preserve islets, but further research is needed. Aim of the studyThis study was projected to investigate the new diterpenoid scoparicol E from S. dulcis and examined its islet-protective effect and the potential mechanism both in vitro and in vivo. MethodsThe structure of the novel diterpenoid scoparicol E was clarified by employing a wide range of spectroscopic methods. Using CCK-8 tests, cytotoxicity and antiapoptotic activity of scoparicol E were detected. Serum biochemical analysis and pathologic examination were performed to study the protective effect of scoparicol E against islet damage. The specific mechanism of action of scoparicol E was investigated through the mitochondrial membrane potential, Annexin V-FITC flow cytometry, and western blotting. ResultsScoparicol E reduced MLD-STZ-induced hyperglycemia in mice and increased insulin and islet apoptosis. Scoparicol E effectively suppressed the Bax/Bcl-2/Caspase-3 pathway, according to the in vivo western blot investigation. Scoparicol E showed significant antiapoptotic action in vitro. We also showed that scoparicol E might prevent islet cells from dying by inhibiting the Bax/Bcl-2/Caspase-3 pathway. The Annexin V-FITC flow cytometry results revealed that MIN6 cell apoptosis was considerably decreased following scoparicol E intervention, showing anti-islet cell apoptosis action. Furthermore, the Caspase-3-mediated apoptosis pathway depends on cytochrome c and the potential of the mitochondrial membrane. Scoparicol E prevented the release of cytochrome c, restored the mitochondrial membrane potential, and prevented MIN6 cell apoptosis. ConclusionWe demonstrated the new diterpenoid scoparicol E could protect islet cells apoptosis by modulating the Bax/Bcl-2/Caspase-3 pathway.

Diabetology and Nanotechnology: A Compelling Combination

Abstract:: The convergence of diabetology and nanotechnology has emerged as a promising synergy with the potential to revolutionize the management and treatment of diabetes mellitus. Diabetes, a complex metabolic disorder affecting millions worldwide, necessitates innovative approaches to enhance monitoring, diagnosis, and therapeutic interventions. Nanotechnology, a burgeoning field that manipulates materials at the nanoscale, offers unprecedented opportunities to address the challenges posed by diabetes. This abstract explores the multifaceted interface between diabetology and nanotechnology, highlighting key areas of integration. Nanotechnology has paved the way for the development of advanced glucose monitoring systems with enhanced accuracy, sensitivity, and patient convenience. Miniaturized biosensors and implantable devices equipped with nanoscale materials enable continuous and real-time glucose monitoring, empowering individuals with diabetes to make timely and informed decisions about their dietary and insulin management. Furthermore, nanotechnology has facilitated breakthroughs in targeted drug delivery, addressing the limitations of conventional therapies in diabetes treatment. Nano-sized drug carriers can improve bioavailability, enable controlled release, and enhance the selectivity of therapeutic agents, minimizing side effects and optimizing treatment outcomes. Moreover, nanoengineered materials have opened avenues for tissue engineering and regenerative medicine, offering the potential to restore damaged pancreatic islets and insulin-producing cells. The amalgamation of diabetology and nanotechnology also holds promise for early disease detection and prevention. Nanoscale diagnostic tools, such as biomarker-based nanoprobes and lab-onchip devices, offer rapid and accurate detection of diabetes-related biomolecules, enabling timely interventions and reducing the risk of complications. However, this compelling combination also presents challenges that warrant careful consideration. Safety, biocompatibility, regulatory approval, and ethical implications are crucial factors that demand meticulous evaluation during the translation of nanotechnology-based solutions into clinical practice. In conclusion, the integration of diabetology and nanotechnology represents a transformative paradigm that has the potential to reshape the landscape of diabetes management. By harnessing the unique properties of nanoscale materials, researchers and clinicians are poised to usher in an era of personalized and precise diagnostics, therapeutics, and preventive strategies for diabetes mellitus. As advancements in nanotechnology continue to unfold, the journey towards realizing the full potential of this compelling combination remains an exciting frontier in medical science.

Genetic lineage tracing identifies adaptive mechanisms of pancreatic islet β cells in various mouse models of diabetes with distinct age of initiation.

During the pathogenesis of type 1 diabetes (T1D) and type 2 diabetes (T2D), pancreatic islets, especially the β cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet (HFD) and streptozotocin (STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of islet β cells. Cre-LoxP systems were used to generate islet cell type-specific (α, β, or δ) green fluorescent protein (GFP)-labeled mice for genetic lineage tracing, thereinto β-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing (scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled β cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of β cells and some of which transdifferentiated into a or δ cells in both youth- and adulthood-initiated mice while this phenomenon was barely observed in HFD models. β cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into β cells in STZ-treated mice (both youth- and adulthood-initiated). In addition to the re-dedifferentiation of β cells, it is also highly likely that these "α or δ" cells transdifferentiated from pre-existing β cells could also re-trans-differentiate into insulin-producing β cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of β cells. Our findings shed light on how islet β cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.

Pancreas Histology of Hyperglycemia of Mice (Mus musculus L.) After Treatment Basil (Ocimum x africanum Lour.) Leaf Extract and Papaya (Carica papaya L.)

Hyperglycemia is a condition in which the level of glucose in the blood is abnormally high. Hyperglycemia is caused by disturbances in the metabolic system in secreting insulin. Hyperglycemia if left unchecked can cause a disease which is usually called diabetes. Basil (Ocimum x africanum Lour.) and papaya (Carica papaya L.) leaf extracts can reduce blood glucose levels in people with diabetes mellitus because they contain active compounds of flavonoids, alkaloids and tannins which function as anti-diabetics. The aim of this study was to examine the effectiveness of the effects of basil and papaya leaf in affecting the level of islet damage, and repairing pancreatic histological damage in hyperglycemic mice. This study used a completely randomized design with 5 treatment groups and 5 replications. Group K(N) as normal control, group K(+) as positive control, group K (-) as negative control, group P 1 (alloxan induced and treated with ethanol extract of basil leaves 24.5 mg/35g BW mice) 14 days oral) , P 2 group (induced by alloxan and treated with papaya leaf ethanol extract 24.5 mg/35 g BW mice (14 days oral). Data on the level of histological damage to the pancreas of hyperglycemic mice were analyzed using the Kruskal-Wallis method and the Wilcoxon-MannWhitney test at a significant level of 5%. Data histological appearance of the Langerhans were analyzed descriptively.The results showed basil leaf extract and papaya had an effect on the level of damage to the pancreas of mice, basil leaf extract was effective compared to papaya in histological repair of the mice pancreas

Extract and fraction of cashew nut testa ameliorate the hyperglycemic mice induced by Streptozotocin and high-fat diet

Drug strategy is a standard method for treating type 2 diabetes mellitus (T2D), a non-communicable disease with increasing prevalence, which may cause side effects. Therefore, natural compounds with limited adverse effects have come back into vogue for treating T2D. This study aims to evaluate the effects on rehabilitating hyperglycemic mice of cashew nut testa (husk) extract and fraction known as potential bio-substances for improvement in T2D. First, the hyperglycemic mice were induced with a high-fat diet (HFD) for 4 weeks and then were injected with streptozotocin (STZ, dozen for injection was 40 mg/kg/week) for 2 weeks. Next, the confirmed hyperglycemic mice were treated with pioglitazone (HG+PG group), total extract (HG+TE group), and saponin-rich fraction (HG+SRF group) for 3 weeks. Then, the evaluation was based on body mass; blood glucose (BG) level; BG tolerance, lipid profile, pancreatic histology and the expression IRS-1 in the pancreas. The results showed that body mass and BG level significantly increased in hyperglycemic mice. After substance treatment, there was no change in body mass in TE and SRF groups. However, BG level of HG+TE group mice significantly decreased compared to hyperglycemic mice and only BG tolerance of HG+SRF group was improved. Besides, HG+TE and HG+SRF groups modulated the triglyceride, HDL and LDL close to those expressed in normal mice. In addition, histological images of the pancreas revealed the restoration in both HG+TE and HG+SRF groups. Simultaneously, the IRS-1 expression in HG+TE group pancreas was restored to its expression in normal mice. These results demonstrate that the TE and SRF of cashew nut testa could ameliorate BG, lipid profile and pancreatic IRS-1 expression and restore the damaged pancreas and islets in hyperglycemic mice.

Tianhuang formula ameliorates non-alcoholic fatty liver diseases in type 2 diabetic mice through CRLS1-ATF3/ChREBP pathway

ObjectiveTianhuang Formula (THF) is a hospital formula summarized by Professor Jiao Guo's 30 years of clinical experience. Some studies have shown that it can alleviate dyslipidemia in the body. The purpose of this study is to confirm whether THF can improve non-alcoholic fatty liver diseases (NAFLD) in type 2 diabetic mice induced by high-fat diet (HFD)/streptomycin (STZ) and to clarify its potential mechanism. MethodsAfter induction of diabetes, mice were administrated with THF (60 ​mg/kg or 120 ​mg/kg) once daily for 10 weeks. Blood glucose (FBG), glucose tolerance, and insulin resistance (IR) were assayed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Blood lipids, alanine transaminase (ALT), and aspartate transaminases (AST) were detected. Serum fasting insulin (INS) and adiponectin (APN) levels were measured using ELISA. Histological changes in liver and pancreatic islets were observed by H&E staining, followed by Oil Red O staining for liver lipid quantification and periodic acid-Schiff (PAS) staining to detect glycogen accumulation. Western blotting detected the levels of fatty cardiolipin synthase 1 (CRLS1), transcription factor activator 3 (ATF3), and carbohydrate-responsive element binding protein (ChREBP) in the liver. The mRNA transcripts of hepatic inflammatory factors, lipogenesis and lipolysis-related genes, and gluconeogenic enzyme-phosphoenolpyruvate carboxykinase (PEPCK), CRLS1, ATF3, and ChREBP mRNA levels were evaluated by RT-qPCR. ResultsTHF restored impaired glucose tolerance and insulin resistance, respectively. There was an improvement in HFD/STZ-induced liver and islet damage, high serum HDL-C and ANP levels, and a significant decrease in FBG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), FFA, INS, ALT, and AST, and lipid droplet counts in the T2DM mice treated with THF. CREBBP binding protein ATF3 mediated the insulin resistance signaling pathway, which regulated glucose and lipid metabolism in the liver. THF upregulated CRLS1, and ChREBP downregulated the expression of downstream ATF3 in the liver. RT-qPCR analysis also systemically indicated that THF suppressed the pathway and key regulators related to inflammation, lipid accumulation, and gluconeogenesis. ConclusionOur findings demonstrated that THF ameliorated lipid profile and attenuated liver steatosis in T2DM mice through CRLS1-ATF3/ChREBP pathway activation.

P.14a: Small molecule inhibitor of toll-like receptor 4, TAK-242, attenuates islet damage due to IBMIR and immune responses

P.14a: Small molecule inhibitor of toll-like receptor 4, TAK-242, attenuates islet damage due to IBMIR and immune responses

Pancreatic Islet Viability Assessment Using Hyperspectral Imaging of Autofluorescence.

Islets prepared for transplantation into type 1 diabetes patients are exposed to compromising intrinsic and extrinsic factors that contribute to early graft failure, necessitating repeated islet infusions for clinical insulin independence. A lack of reliable pre-transplant measures to determine islet viability severely limits the success of islet transplantation and will limit future beta cell replacement strategies. We applied hyperspectral fluorescent microscopy to determine whether we could non-invasively detect islet damage induced by oxidative stress, hypoxia, cytokine injury, and warm ischaemia, and so predict transplant outcomes in a mouse model. In assessing islet spectral signals for NAD(P)H, flavins, collagen-I, and cytochrome-C in intact islets, we distinguished islets compromised by oxidative stress (ROS) (AUC = 1.00), hypoxia (AUC = 0.69), cytokine exposure (AUC = 0.94), and warm ischaemia (AUC = 0.94) compared to islets harvested from pristine anaesthetised heart-beating mouse donors. Significantly, with unsupervised assessment we defined an autofluorescent score for ischaemic islets that accurately predicted the restoration of glucose control in diabetic recipients following transplantation. Similar results were obtained for islet single cell suspensions, suggesting translational utility in the context of emerging beta cell replacement strategies. These data show that the pre-transplant hyperspectral imaging of islet autofluorescence has promise for predicting islet viability and transplant success.

Aloe vera Gel Ameliorates Fat-Rich and High Fructose (FRHF) Diet-Induced Pancreatic and Splenic Damage in Mice

High-fat diet alone or in combination with high fructose has been known to induce diabetes, obesity, hypertension, and immune dysfunction. The study evaluates the role of Aloe vera in fat-rich and high fructose diet-induced (FRHFD) hyperglycemias in addition to testicular and splenic morphology in mice. Twenty BALB/c Mice were randomly distributed into four groups (n=5). The groups were fed on a normal diet, FRHFD, FRHFD + 10 g A. vera, and FRHFD + 20 g A. vera for 10 weeks. All the mice were sacrificed a day after the 10 weeks of treatment. The result showed that mice fed on FRHFD plus A. vera had a significantly lower (p&lt;0.05) blood glucose level relative to the FRHFD-fed mice. The mice fed on FRHFD plus A. vera had a significantly lower (p&lt;0.05) blood glucose level relative to the FRHFD-fed mice. Aloe vera was found to ameliorate FRHFD-induced pancreatic islet and acini damage. It also prevented distorted lymphoid cells and testicular damage induced by FRHFD. Aloe vera prevents hyperglycemia and protects pancreatic islets in FRHFD-fed mice. It further prevents immune dysfunction and protects against testicular damage. Hence, A. vera supplementation could be an alternative and/or complementary therapy for hyperglycemia-related disorders.