Search Results (796)

Background: Diabetes mellitus is associated with worse outcomes after cardiac arrest. Hyperglycemia, diabetes treatments and other long-term sequalae may contribute to this association. We sought to determine the acute effect of diabetes on the return of spontaneous circulation (ROSC) and post-arrest cardiac function in a rat cardiac arrest model. Methods: Eighteen male Wistar rats were utilized, and 12 underwent the induction of type II diabetes for 10 weeks through a high-fat diet and the injection of streptozotocin. The carotid artery flow and femoral arterial pressure were measured. Seven minutes of asphyxial cardiac arrest was induced. An external cardiac compression was performed via an automated piston. Post-ROSC, epinephrine was titrated to a mean arterial pressure (MAP) of 70 mmHg. Data was analyzed using the Mann–Whitney test. The significance was set at p ≤ 0.05. Results: The rate of the ROSC was significantly lower in animals with diabetes, 50% compared to 100% in non-diabetics. Additionally, it took significantly longer to achieve the ROSC in diabetics, p = 0.034. In animals who survived, the cardiac function was reduced, as indicated by an increased epinephrine requirement, p = 0.041, and a decreased cardiac output at the end of the experiment, p = 0.017. The lactate, venous and arterial pressures, heart rate and carotid flow did not differ between groups at 2 h. Conclusions: Diabetes negatively affects the survival from cardiac arrest. Here, the critical difference was the rate of the conversion to a life-sustaining rhythm and the achievement of the ROSC. The post-ROSC cardiac function was depressed in diabetic animals. Interventions targeted at improving defibrillation success may be important in diabetics. Full article

Diabetic encephalopathy affects over 40% of diabetic patients globally, yet effective treatments remain critically limited. This study investigated the synergistic neuroprotective potential of alpha-lipoic acid (ALA) and metformin through the coordinated activation of Nrf2 and AMPK signaling pathways in type 2 diabetes mellitus (T2DM)-induced encephalopathy. Using a clinically relevant streptozotocin-nicotinamide-induced T2DM rat model, sixty male Sprague–Dawley rats were randomly assigned to five groups: control, diabetic, ALA-treated (300 mg/kg), metformin-treated (50 mg/kg), and combination-treated groups over eight weeks. Combination therapy produced statistically validated synergistic effects with significant interaction terms (p < 0.01) across all evaluated parameters. Nuclear Nrf2 translocation increased 3.9-fold and AMPK phosphorylation rose 3.2-fold compared to monotherapies, surpassing mathematical additivity. Mitochondrial function was remarkably restored, with ATP production increasing to 92% of control levels. Cognitive performance was normalized, with spatial memory approaching control values. Combination index analysis (CI < 1.0) confirmed true synergistic interactions across molecular, cellular, and behavioral endpoints. These findings establish a novel convergent mechanism providing compelling evidence for combination ALA–metformin therapy as an innovative treatment strategy for diabetes-associated neurodegeneration. Full article

The treatment of type 1 diabetes through pancreatic islet transplantation faces significant limitations, including donor organ shortages and poor islet survival due to post-transplantation loss of extracellular matrix support and inadequate vascularization. Developing biocompatible scaffolds that mimic the native islet microenvironment could substantially improve transplantation outcomes. This study aimed to create and evaluate decellularized (DCL) matrices from porcine organs as potential platforms for islet transplantation. Porcine lung and pancreatic tissues were decellularized using four different protocols combining detergents (Triton X-100, SDS and SDC) with optimized incubation times. The resulting matrices were characterized through DNA quantification and histological staining (H&E and Van Gieson). Islet viability was assessed in vitro using Live/Dead staining after 3 and 7 days of culture on the matrices. In vivo biocompatibility was evaluated by implanting matrices into rat omentum or peritoneum, with histological analysis at 1-, 4-, and 8 weeks post-transplantation. Protocols 3 (for lung tissue) and 4 (for pancreas tissue) demonstrated optimal decellularization efficiency with residual DNA levels below 8%, while preserving the collagen and elastin networks. In vitro, islets cultured on decellularized lung matrix had maintained 95% viability by day 7, significantly higher than the controls (60%) and pancreatic matrix (83%). The omentum showed superior performance as an implantation site, exhibiting minimal inflammation and fibrosis compared to the peritoneum sites throughout the 8-week study period. These findings establish DCL as a promising scaffold for islet transplantation due to its superior preservation of ECM components and excellent support of islet viability. This work provides a significant step toward developing effective tissue-engineered therapies for diabetes treatment. Full article

It is well recognized that patients with type 2 diabetes mellitus (T2DM) exhibit significant impairment of immune function resulting in a higher frequency of infections. We hypothesize in this study that a likely contributor to immune dysfunction in T2DM is alteration of T lymphocyte signaling functions induced by chronic hyperglycemia. In this study we have utilized the established UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model of human T2DM to investigate whether progressive hyperglycemia diminishes T cell receptor (TCR)-releasable endoplasmic reticulum (ER) Ca²⁺ stores, an essential early antigen-stimulated signal driving T cell activation. Furthermore, results from this study demonstrate that chronic hyperglycemia markedly alters the expression profile of the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) Ca²⁺ ion pumps, which are the major enzymatic ion transporters maintaining replenished TCR-sensitive Ca²⁺ pools. We conducted companion experiments using Jurkat T lymphocytes exposed to high glucose which allowed finer resolution of early disruptions to ER Ca²⁺ store integrity and greater clarity on SERCA isoform-specific roles in diabetes-induced Ca²⁺ signal dysregulation. In summary, these experiments suggest that hyperglycemia in T2DM drives an ER stress state manifesting in reduced expression of the SERCA pumps, erosion of ER Ca²⁺ stores and culminating in T cell and immune dysfunction. Full article

Mao Jian Green Tea flavonoids (MJGT_F) contain luteolin, luteolin-7-O-glucoside, eriodictyol, and eriodictyol-7-O-glucoside, among which the first three components have hypoglycemic effects; however, the overall hypoglycemic potential of MJGT_F remains unclear. This study demonstrated that MJGT_F inhibited α-glucosidase in vitro and improved metabolic parameters in a dose-dependent manner in T2DM (type 2 diabetes mellitus) rats (reducing blood glucose, triglyceride, total cholesterol, low-density lipoprotein, insulin, and the homeostatic model assessment of insulin resistance; increasing high-density lipoprotein, insulin sensitivity index, and glucagon-like peptide-1). High-dose MJGT_F (MJGT_F_H) showed optimal efficacy. Mechanistically, MJGT_F_H activated the AMPK pathway, evidenced by a significant increase in the p-AMPK/AMPK ratio and downregulation of hepatic gluconeogenic enzymes G6Pase and PEPCK. These coordinated effects collectively suggest enhanced hepatic glucose utilization and suppression of glucose overproduction. MJGT_F_H also modulated gut microbiota by enriching beneficial taxa (e.g., Akkermansia muciniphila, 11.17-fold vs. metformin) and reducing pathogens like Enterobacteriaceae. These findings highlight MJGT_F’s dual regulatory roles in glucose metabolism and microbiota, supporting its potential for diabetes management. Full article

Type 1 diabetes (T1D) is caused by autoimmune-mediated destruction of pancreatic β-cells, resulting in insulin deficiency. While islet transplantation presents a potential therapeutic approach, its clinical application is impeded by limited donor availability and the risk of immune rejection. This study proposes an innovative islet encapsulation strategy that utilizes decellularized porcine pancreatic extracellular matrix (pECM) as the sole biomaterial to engineer bioactive, immunoprotective microcapsules. Rat islets were encapsulated within pECM-based microcapsules using the electrospray technology and were compared to conventional alginate-based microcapsules in terms of viability, function, and response to hypoxic stress. The pECM microcapsules maintained a spherical morphology, demonstrating mechanical robustness, and preserving essential ECM components (collagen I/IV, laminin, fibronectin). Encapsulated islets exhibited sustained viability and superior insulin secretion over a two-week period compared to alginate controls. The expression of key β-cell transcription factors (PDX1, MAFA) and structural integrity were preserved. Under hypoxic conditions, pECM microcapsules significantly reduced islet apoptosis, improved structural retention, and promoted functional recovery, likely due to antioxidant and ECM-derived cues inherent to the pECM. In vivo transplantation in immunocompetent mice confirmed the biocompatibility of pECM microcapsules, with minimal immune responses, stable insulin/glucagon expression, and no adverse systemic effects. These findings position pECM-based microencapsulation as a promising strategy for creating immunoprotective, bioactive niches for xenogeneic islet transplantation, with the potential to overcome current limitations in cell-based diabetes therapy. Full article

Background and Objectives: We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a nutritional and disease modifying supplement an important question to be addressed is what is the preferred source of omega-3 PUFAs? Methods: Using a type 2 diabetic rat model and early and late intervention protocols we examined the effect of dietary treatment with omega-3 PUFAs derived from menhaden (fish) oil (MO), krill oil (KO), algal oils consisting primarily of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or combination of EPA + DHA, or pharmaceutical-derived ethyl esters of EPA, DHA or combination of EPA + DHA. Nerve related endpoints included motor and sensory nerve conduction velocity, heat sensitivity of the hind paw, intraepidermal nerve density, cornea nerve fiber length, and cornea sensitivity. Vascular reactivity to acetylcholine and calcitonin gene-related peptide by epineurial arterioles that provide blood to the sciatic nerve was also examined. Results: The dose of each omega-3 PUFA supplement increased the content of EPA, docosapentaenoic acid (DPA), and/or DHA in red blood cell membranes, serum and liver. Diabetes caused a significant decrease of 30–50% of neural function and fiber occupancy of the skin and cornea and vascular reactivity. Treatment with MO, KO or the combination of EPA + DHA provided through algal oil or ethyl esters provided significant improvement of each neural endpoint and vascular function. Algal oil or ethyl ester of EPA alone was the least effective with algal oil or ethyl ester of DHA alone providing benefit that approached combination therapies for some endpoints. Conclusions: We confirm that omega-3 PUFAs are an effective treatment for DPN and sources other than fish oil are similarly effective. Full article

The effective healing of chronic wounds requires balancing antimicrobial activity with tissue regeneration. In this study, we developed a novel, eco-friendly synthesis method using Artemisia argyi extract to produce silver nanoparticles (AgNPs), addressing toxicity concerns associated with conventional chemical synthesis methods. Through optimization of multiple synthesis parameters, monodisperse spherical AgNPs with an average diameter of 6.76 ± 0.27 nm were successfully obtained. Plant-derived compounds from Artemisia argyi extract acted as efficient mediators for both reduction and stabilization, yielding nanoparticles with high crystallinity. The synthesized AgNPs exhibited potent antibacterial activity against both Gram-negative and Gram-positive bacteria, with minimum inhibitory concentrations of 8 μg/mL against Escherichia coli and 32 μg/mL against Staphylococcus aureus, while maintaining high biocompatibility with L929 fibroblasts at concentrations ≤ 8 μg/mL. When integrated into polylactic acid/collagen type I (PLA/Col1) nanofibrous matrices, the optimized 0.03% AgNPs/PLA/Col1 dressing significantly accelerated wound healing in a diabetic rat model, achieving 94.62 ± 2.64% wound closure by day 14 compared to 65.81 ± 1.80% observed in untreated controls. Histological analyses revealed a dual-functional mechanism wherein controlled silver ion release provided sustained antibacterial protection, while concurrently promoting tissue regeneration characterized by enhanced collagen deposition, reduced inflammation, and increased neovascularization. This innovative approach effectively addresses critical challenges in diabetic wound care by providing simultaneous antimicrobial and regenerative functions within a single biomaterial platform. Full article

Background/Objectives: Chronic kidney disease (CKD) is twice as prevalent in individuals with obesity-associated non-alcoholic fatty liver disease (Ob-NAFLD), highlighting the need to determine the link and mechanisms of kidney injury as well as explore therapies. Metformin, a first-line treatment for type 2 diabetes, shows promise in managing NAFLD, but its renal benefits in Ob-NAFLD remain unclear. This study investigates the impact of Ob-NAFLD on kidney injury and assesses the potential protective effects of metformin. Methods: Five-week-old female Zucker rats (obese fa/fa and lean Fa/Fa) were fed an AIN-93G diet for 8 weeks to induce Ob-NAFLD, then fed the diet with Metformin for 10 weeks. Kidneys were collected for histopathological and biochemical analyses. Results: Histopathological studies showed increased tubular injury, mesangial matrix expansion, and fibrosis in kidneys with Ob-NAFLD compared to lean control (LC) rats. Immunohistochemistry further revealed an elevated macrophage and neutrophil infiltration and increased levels of nitrotyrosine and p22phox in Ob-NAFLD kidneys. Furthermore, Ob-NAFLD rat kidneys showed upregulation of TNF-α and CCL2 genes and increased levels of caspase-3 (total and cleaved). Interestingly, metformin treatment significantly decreased TNF-α mRNA and blunted nitrotyrosine levels, and modestly reduced immune cell infiltration in Ob-NAFLD. Conclusions: These findings indicate that Ob-NAFLD promotes CKD as evidenced by tubular injury, oxidative stress, inflammation, and fibrosis. While short-term metformin treatment showed anti-oxidative and anti-inflammatory effects in Ob-NAFLD, its impact on structural kidney damage was limited, highlighting the need for longer treatment or alternative therapeutics such as oxidant scavengers and anti-inflammatory drugs to effectively mitigate renal pathologies. Full article

Background/Objectives: In the context of diabetes, a multifactorial metabolic disorder with significant clinical implications, the present study investigates the hypoglycemic effects of a synthetic sulfonamide (S) administered individually and in combination with Salvia officinalis extract, compared to metformin as a standard therapeutic agent. Methods: An in vivo model of experimentally induced diabetes using alloxan was applied to Wistar female rats, divided into six experimental groups, including a healthy control group and a diabetes-induced, untreated group. Plasma concentrations of metformin and sulfonamide were quantified by high-performance liquid chromatography. The plasma steady-state concentrations of the pharmaceutical agents and their correlation with hypoglycemic effect were evaluated. Results: The combination of the synthetic sulfonamide (S) with Salvia officinalis extract resulted in the greatest reduction in blood glucose level (average value of 50.2%) compared to S (40.6%) or metformin (36.4%). All treatments demonstrated statistically significant differences in blood glucose levels compared to the diabetes-induced untreated group (p < 0.05). Pharmacokinetic analysis revealed a larger volume of distribution for the synthetic sulfonamide S (23.92 ± 8.40 L) compared to metformin (16.07 ± 5.60 L), consistent with its physicochemical properties. No significant correlation was found between plasma drug levels and glycemic response (p > 0.05). Conclusions: Our findings support the potential of combining standard therapeutic agents with natural alternatives such as Salvia officinalis to achieve improved glycemic control through complementary mechanisms. To the best of our knowledge, this is the first in vivo study to evaluate the combined effects of a sulfonylurea-type compound and Salvia officinalis extract in a diabetic animal model. 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

Peptidylarginine deiminase 4 (PAD4) catalyzes protein citrullination, a post-translational modification implicated in type 1 diabetes mellitus (T1DM). This study examined PAD4 expression and activity in the pancreas of streptozotocin (STZ)-induced diabetic Wistar rats. Animals were divided into three groups: (A) STZ-induced diabetic rats (60 mg/kg, i.p.), (B) non-diabetic controls, and (C) diabetic rats treated with Cl-amidine (5 mg/kg), a pan-PAD inhibitor, from week six post-induction. Analyses included PAD4 mRNA and protein expression, citrullinated histone H3 (CitH3), calcium concentration, and neutrophil elastase activity. Diabetic rats exhibited increased PAD4 expression, CitH3 levels, and NETosis markers, alongside reduced pancreatic calcium, suggesting calcium consumption during PAD4 activation. Cl-amidine treatment attenuated NETosis. These results implicate PAD4 in T1DM pathogenesis via NETosis and support the utility of STZ-induced diabetic rats as a model for PAD4-targeted studies. Cl-amidine may represent a promising therapeutic approach to reduce pancreatic inflammation in T1DM. Full article

Type 2 diabetes mellitus is a growing global health concern, with diabetic retinopathy (DR) representing a major microvascular complication that contributes significantly to vision impairment. Oxidative stress plays a critical role in the pathogenesis of DR, which is associated with changes in vascularization-associated molecules, such as iNOS, VEGF, and MMP-9. The present study investigates the therapeutic potential of bilberry (Vaccinium myrtillus L.) extract—rich in anthocyanins—applied for 14 days on blood glucose levels, lipid profile, and retinal oxidative stress (lipid peroxidation (TBARS) and advanced oxidized protein products (AOPPs)) in a streptozotocin/nicotinamide (STZ/NA)-induced diabetes rat model. Results showed a significant reduction in non-fasting blood glucose, retinal TBARS, and AOPP levels, and normalization of VEGF and MMP-9 expression in bilberry-treated diabetic rats. Bilberry extract also partially improved lipid profile by lowering LDL levels. However, no significant effects on fasting glucose or serum insulin were observed. These findings suggest that bilberry extract may offer protective effects against oxidative retinal damage and could serve as a complementary approach in managing early diabetic retinopathy. Full article

Background: Mexico, one of the world’s most biodiverse countries, holds a rich tradition of using medicinal plants to manage chronic diseases such as type 2 diabetes and hypertension. Despite their historical significance, the scientific validation of these plants’ mechanisms and safety remains limited. Natural products have shown potential in improving insulin sensitivity, reducing insulin resistance, and promoting vasodilation. Prostachea livida (Lindl.) W.E.Higgins, a native orchid, is believed to possess therapeutic properties, yet its pharmacological effects are unexplored. Objective: The current investigation is aimed to bridge traditional knowledge and scientific evidence by investigating the antidiabetic, vasodilatory and antihypertensive activities of a 1:1 dichloromethane and methanol extract from Prosthechea livida bulbs, alongside an evaluation of its pharmacological safety. Methods: Antidiabetic effects of the extract were evaluated in a non-insulin-dependent mouse model using a 100 mg/kg dose. Vasodilatory activity was assessed ex vivo using rat aortic rings, exploring its mechanism through calcium channel blockade. Antihypertensive effects were evaluated in spontaneously hypertensive rats, while acute and subacute toxicity tests were conducted in a murine model. Results: The extract significantly reduced glycemia between 1, 3, 5, and 7 h compared to the positive control (* p = 0.04, *** p < 0.001) and induced vasorelaxation but showed no antihypertensive effects in vivo. Toxicity tests indicated no severe damage, though elevated transaminase activity and increased liver weight were observed. Histopathological analysis revealed minimal hepatocellular lesions with active regeneration. Conclusions: Prosthechea livida demonstrates potential in the discovery of active metabolites to treat diabetes, with significant hypoglycemic and vasorelaxant effects and promising pharmacological safety. Further research is needed to fully understand its therapeutic applications and ensure its safe integration. Full article

Obesity is a global health concern that elevates the risk of noncommunicable diseases (NCDs) such as type 2 diabetes, cardiovascular disease, and certain cancers. Phaseolus vulgaris (white bean) contains α-amylase inhibitors (αAIs) that can reduce carbohydrate digestion and absorption, potentially mitigating obesity and metabolic syndrome. This study investigated the impact of P. vulgaris extract (PVE) on obese rats. Male Wistar rats were fed either a standard diet (SD) or a cafeteria diet (CAF) for 17 weeks to induce obesity. Subsequently, rats in each dietary group were randomly assigned to receive a vehicle, low-dose PVE (200 mg/kg), high-dose PVE (300 mg/kg), or metformin (200 mg/kg) via an oral gavage for 6 weeks. The CAF group exhibited significantly greater weight gain compared to the SD group. In the CAF group, a low dose of PVE lowered postprandial glycemia during an oral glucose tolerance test (OGTT) at 60 and 120 min and decreased food and energy intake during weeks 17–20 and 18–19, respectively. In the SD group, a high dose of PVE reduced glycemia at 90 min in the OGTT, as well as body weight gain, food intake, and energy intake during week 17. However, the overall areas under the glucose curves in the OGTT were not significantly different across treatment groups (p > 0.05), and while individual time points showed changes, the overall glucose exposure (AUC) was not significantly altered. In conclusion, the αAIs present in P. vulgaris demonstrate the potential to reduce body weight, weight gain, glycemia, total cholesterol, and triglycerides in vivo, but in the CAF group, neither PVE dose significantly altered the TC or TG. This study provides strong support for further exploring Phaseolus vulgaris extract as a valuable functional ingredient in the food industry, particularly for developing products that aid in weight management and glycemic control. Full article