Diabetic Rat Model Research Articles

Ferric Iron/Shikonin Nanoparticle-Embedded Hydrogels with Robust Adhesion and Healing Functions for Treating Oral Ulcers in Diabetes.

Oral ulcers can be addressed using various biomaterials designed to deliver medications or cytokines. Nevertheless, the effectiveness of these substances is frequently limited in many patients due to poor adherence, short retention time in the mouth, and less-than-optimal drug efficacy. In this study, a new hydrogel patch (FSH3) made of a silk fibroin/hyaluronic acid matrix with light-sensitive adhesive qualities infused with ferric iron/shikonin nanoparticles to enhance healing effects is presented. Initially, this hydrogel forms an adhesive barrier over mucosal lesions through a straightforward local injection, solidifying when exposed to UV light. Subsequently, FSH3 demonstrates superior reactive oxygen species elimination and near-infrared photothermal bactericidal activity. These characteristics support bacterial elimination and regulate oxidative levels, promoting a wound's progression from inflammation to tissue regeneration. In a diabetic rat model mimicking oral ulcers, FSH3 significantly speeds up healing by adjusting the inflammatory environment of the injured tissue, maintaining balance in oral microbiota, and promoting faster re-epithelialization. Overall, the light-sensitive FSH3 hydrogel shows potential for rapid wound recovery and may transform therapeutic methods for managing oral ulcers in diabetes.

Zinc-based Polyoxometalate Nanozyme Functionalized Hydrogels for optimizing the Hyperglycemic-Immune Microenvironment to Promote Diabetic Wound Regeneration.

In diabetic wounds, hyperglycemia-induced cytotoxicity and impaired immune microenvironment plasticity directly hinder the wound healing process. Regulation of the hyperglycemic microenvironment and remodeling of the immune microenvironment are crucial. Here, we developed a nanozymatic functionalized regenerative microenvironmental regulator (AHAMA/CS-GOx@Zn-POM) for the effective repair of diabetic wounds. This novel construct integrated an aldehyde and methacrylic anhydride-modified hyaluronic acid hydrogel (AHAMA) and chitosan nanoparticles (CS NPs) encapsulating zinc-based polymetallic oxonate nanozyme (Zn-POM) and glucose oxidase (GOx), facilitating a sustained release of release of both enzymes. The GOx catalyzed glucose to gluconic acid and (H₂O₂), thereby alleviating the effects of the hyperglycemic microenvironment on wound healing. Zn-POM exhibited catalase and superoxide dismutase activities to scavenge reactive oxygen species and H₂O₂, a by-product of glucose degradation. Additionally, Zn-POM induced M1 macrophage reprogramming to the M2 phenotype by inhibiting the MAPK/IL-17 signaling diminishing pro-inflammatory cytokines, and upregulating the expression of anti-inflammatory mediators, thus remodeling the immune microenvironment and enhancing angiogenesis and collagen regeneration within wounds. In a rat diabetic wound model, the application of AHAMA/CS-GOx@Zn-POM enhanced neovascularization and collagen deposition, accelerating the wound healing process. Therefore, the regenerative microenvironment regulator AHAMA/CS-GOx@Zn-POM can achieve the effective conversion of a pathological microenvironment to regenerative microenvironment through integrated control of the hyperglycemic-immune microenvironment, offering a novel strategy for the treatment of diabetic wounds.

"Evaluation of the effects of pioglitazone on perivascular adipose tissue function, properties and structure in a rat model of type-2 diabetes."

Perivascular adipose tissue (PVAT) plays an important role in many physiological and pathological processes, such as regulation of vascular tone. The aim of this study is to evaluate the effects of pioglitazone on functional, structural, and biochemical properties of PVAT in an experimental model of type-2 diabetes (T2DM). T2DM was induced by high-fat-diet/low-dose-streptozotocin (HFD/STZ) in rats, and pioglitazone (20mg/kg/p.o.) was administered for 6 weeks. Changes in biochemical parameters, PVAT-mass, vascular-reactivity in thoracic-aorta as well as PVAT adipocytokine and PPARG-expression levels, and histopathology were evaluated. Pioglitazone administration improved blood glucose and lipid profiles in T2DM. Pioglitazone did not change the anticontractile effect of PVAT on aortic contractile reactivity and besides, had no influence on endothelium-dependent and -independent relaxation responses. Pioglitazone administration increased PVAT-mass and TNF-α levels while adiponectin, leptin, and IL-6 levels were unchanged. Also, a prominent increase was observed in PPARG-expression in T2DM-Pio group. Moreover, pioglitazone decreased liver steatosis, aortic wall thickening and myocardial damage whereas increased adipocyte size and adiposity in PVAT. Overall, pioglitazone treatment changed the mass and in part the inflammatory profile of PVAT but did not modify vasoreactivity in T2DM. This study provides novel findings in relationship with the adipogenic effect of pioglitazone and PVAT function.

Antioxidant effects of a novel pioglitazone analogue (PA9) in a rat model of diabetes: Modulation of redox homeostasis and preservation of tissue architecture

Oxygen-free radicals have been implicated in the initiation of diabetic complications. Thiazolidinediones (TZDs), known for their antidiabetic properties, also demonstrate notable antioxidant and anti-inflammatory effects. Although a recently developed imidazolyl analogue of pioglitazone (PA9) has exhibited superior glucose-lowering efficacy compared to pioglitazone, its antioxidant effects remain unexplored. Thus, the objective of this study is to evaluate the antioxidant properties of PA9 in animal models with diabetes.Rats were randomly separated into the following four groups: control, diabetic, and two groups treated orally with pioglitazone as a standard drug and PA9 for ten days. Upon completion of the experiment, tissues from the liver, heart, brain, pancreas, spleen, and kidneys were collected to assess oxidant/antioxidant markers and histological alterations. The administration of PA9 resulted in a noteworthy reduction in malondialdehyde (MDA) levels compared to the diabetic group (p < 0.05). The group receiving PA9 displayed elevated levels of three antioxidant markers, catalase (CAT), superoxide dismutase (SOD), and total thiol, in pancreatic tissue compared to diabetic rats (p < 0.05).Furthermore, increased content of CAT was evident in the heart (p < 0.05), spleen (p < 0.001), brain, and kidney tissues in the PA9-treated group, along with augmented thiol content in the spleen compared to the diabetic group. Remarkably, no significant histological changes were observed in the liver, pancreas, heart, brain, spleen, and kidneys of the PA9-treated groups relative to diabetic rats. PA9 effectively mitigates oxidative stress, modulates redox homeostasis, and shows promise in preventing diabetic complications. The proven safety profile of this analogue underscores its potential, warranting comprehensive clinical evaluation to thoroughly understand its therapeutic scope and efficacy in the management of diabetes.

Efficacy of Oral Nanoparticle-Encapsulated Insulin in Reducing Oxidative Stress and Enhancing Tissue Integrity in a Diabetic Rat Model.

Diabetes mellitus, a chronic metabolic disorder, leads to systemic organ damage characterized by oxidative stress and structural alterations, contributing to increased morbidity and mortality. Traditional subcutaneous insulin therapy, while managing hyperglycemia, often falls short in addressing the oxidative damage and preventing organ-specific complications. This study evaluates the therapeutic efficacy of a novel oral nanoparticle-mediated insulin (nCOF/Insulin) against these diabetes-induced changes, comparing it with traditional subcutaneous insulin in a streptozotocin (STZ)-induced diabetic rat model. We induced diabetes in Wistar rats, dividing them into four groups: standard control, diabetic control, diabetic treated with subcutaneous insulin, and diabetic treated with oral nanoparticle-mediated insulin (nCOF/Insulin). Assessments included organ and body weights, histopathological examinations, and oxidative stress markers (MDA and PCOs) across various organs, including the brain, muscle, intestine, spleen, heart, liver, kidney, and adrenal glands. Additionally, we evaluated antioxidant parameters (GSH and catalase) and conducted immunohistochemical analysis of E-cadherin to assess intestinal integrity. Our findings reveal that STZ-induced diabetes significantly impacts organ health, with subcutaneous insulin providing limited mitigation and, in some cases, exacerbating oxidative stress. Conversely, oral nCOF/Insulin treatment effectively restored organ and body weights, reduced oxidative stress markers, and mitigated histological damage. This suggests that oral nCOF/Insulin not only offers superior glycemic control but also addresses the underlying oxidative stress. nCOF/Insulin emerges as a promising treatment for diabetes, with the potential to improve patient quality of life by ameliorating oxidative stress and preventing organ-specific complications. This study underscores the need for further investigation into the long-term effects and mechanisms of action of oral nCOF/Insulin, aiming to revolutionize diabetes management and treatment strategies.

Flaxseed extract: A potential therapeutic intervention for type-2 diabetes mellitus and cardiovascular risk reduction in Wistar rats

Introduction: Type 2 diabetes mellitus (T2DM) affects millions of people worldwide, highlighting the importance of dietary interventions. Flaxseed (Linum usitatissimum L.) has shown promise in treating chronic metabolic diseases. This study investigates the therapeutic potential of flaxseed as an antidiabetic agent and its protective effect on cardiovascular diseases. Methods: Rats were randomly divided into five groups: normal fed with drug carrier group (N), diabetes with drug carrier group (D), diabetes with metformin (M) group (D+M), and diabetes with flaxseed extract doses of 100 and 200 mg/kg (D+F1 and D+F2) groups. The diabetic rat model was established by administration of drinking water containing 25% fructose and a single intraperitoneal injection of 100 mg/kg alloxan. After a six-week intervention, the rats were sacrificed to assess the antidiabetic and cardiovascular effects. Results: The doses of 100 and 200 mg/kg flaxseed extract significantly reduced body weight and fasting glucose levels and increased insulin sensitivity index (KITT) compared to the diabetes group (P&lt;0.05). In addition, histological analysis showed a significant improvement and increase in pancreatic beta cells in the treatment group compared to the diabetes group (P&lt;0.05). Flaxseed extract doses of 100 and 200 mg/kg significantly reduced weight gain and insulin resistance, contributing to decreased arterial stiffness and atherogenic index compared to the diabetic group (P&lt;0.05). The hypoglycemic effect suggested a dose-dependent response. Conclusion: Flaxseed extract regulates blood glucose levels probably by enhancing insulin sensitivity and revitalizing damaged pancreatic beta cells. It mitigates cardiovascular risk, by reducing arterial stiffness and atherogenicity.

The potential therapeutic role of Ginkgo biloba extracts on ventral prostate in a rat model of streptozotocin-induced diabetes: A histomorphometric study

The potential therapeutic role of Ginkgo biloba extracts on ventral prostate in a rat model of streptozotocin-induced diabetes: A histomorphometric study

Long-term diabetic hyperglycaemia modifies social behaviour in rats

Diabetes is a known risk factor for cognitive decline and mood disorders. However, the effects of long-term diabetic hyperglycaemia on the various dimensions of social behaviours, such as play or aggression, remains to be fully elucidated. In this study, we evaluated the social behaviour in a nicotinamide-streptozotocin rat model of long-term diabetic hyperglycaemia, in the absence of glucose-lowering treatments. Five months following induction of hyperglycaemia, we scored affiliative/exploratory or aggressive social interactions between pairs of unacquainted rats in a neutral arena. Our results demonstrate alterations in the behaviour of long-term diabetic rats faced with social novelties. Specifically, diabetic hyperglycaemic rats engaged in hyper-sociable and hyper-aggressive encounters. Interestingly, social interactivity was not associated with the degree of hyperglycaemia in affiliative/exploratory or in aggressive social interactions, in our long-term diabetic rat model. Altogether, our data suggest a lack of social appropriateness in long-term diabetic hyperglycaemic rats which is independent of the degree of hyperglycaemia. These findings support the importance of a tight glycaemic control in the management of diabetes at every stage of the disease and enlighten the importance of impaired glycaemic control as a novel metabolic player impacting the neural networks of social behaviours.

Combined Anti-Diabetic and Wound Healing Effects of Binahung Leaf (Basella rubra L.) and Snakehead Fish (Channa striata) Extracts in Alloxan-Induced High-Fat Diet Rats

Diabetes mellitus is a metabolic disease that continues to increase in the world. Lifestyle factors cause diabetes cases to increase uncontrollably. The development of medicines based on natural ingredients has become a subject of study for researchers throughout the world. Meanwhile, binahong leaf extract contains flavonoids and saponins, which can reduce the absorption of glucose. Snakehead fish extract containing albumin also influences the reduction of diabetic wounds. The combination of binahong and snakehead fish extract is expected to synergistically lower blood glucose levels and cure diabetic wounds. Therefore, this study aimed to determine the anti-diabetic and wound healing activity resulting from the combination of binahong leaf and snakehead fish extract in rat models of diabetes induced with alloxan and fat diet. The test animals were divided into six groups with five per group, namely normal, positive, and negative control, as well as dose 1 (snakehead fish 250 mg/kg and binahong extract 100 mg/kg), dose 2 (snakehead fish 250 mg/kg and binahong extract 300 mg/kg), and a single dose of snakehead fish extract 500 mg/kg. The experiment was conducted for 21 days by administering the test solution once a day. The results showed that administering a combination of binahong extract at a dose of 100 mg/kg and snakehead fish at a dose of 500 mg/kg significantly reduced blood glucose levels in diabetic rats (p≤0.05). Treatment using a combination of the two extracts was more effective in lowering blood sugar levels compared to a single dose of snakehead fish extract.

Upregulation of GRP78 is accompanied by decreased antioxidant response and mitophagy promotion in streptozotocin-induced type 1 diabetes in rats

Endoplasmic reticulum stress, oxidative stress, and mitochondrial dysfunction are interconnected processes involved in the pathogenesis of diabetes mellitus (DM). In the present study, we demonstrate a distinct unfolded protein response (UPR) signaling pathways in two mammalian models of DM: β-TC-6 cell line and streptozotocin-induced type 1 diabetes model in rats. However, a feature common to both systems was the upregulation of the GRP78 protein. Moreover, in vivo studies showed the disruption of the antioxidant system and an escalation of mitophagy against the background of a depletion of the level of ATP in pancreatic cells. In conclusion, we suggest that glucotoxic conditions induced GRP78 upregulation, and next cause depletion of the antioxidant pool and disruption of the functioning of antioxidant defense enzymes and in consequence promote mitophagy in pancreatic cells. Therefore, GRP78 may be considered as a potential therapeutic factor in patients with diabetes.

Indoxyl sulfate induces retinal microvascular injury via COX-2/PGE2 activation in diabetic retinopathy

BackgroundDiabetic retinopathy (DR), the principal cause of acquired blindness among the working-age population, is the most frequent microvascular complication of diabetes. Although metabolic disorders are hypothesized to play a role in its pathogenesis, the underlying mechanism remains largely elusive.MethodsTo elucidate the mechanism, we initially compared metabolite profiles of vitreous fluid between 23 patients with DR and 12 non-diabetic controls using liquid chromatography/tandem mass spectrometry, identifying the distinct metabolite indoxyl sulfate (IS). Subsequently, streptozotocin (STZ)-induced diabetic and IS-injected rat models were established to examine the effects of IS on retinal microvasculature. RNA sequencing was conducted to identify potential regulatory mechanisms in IS-treated human retinal endothelial cells (HREC). Finally, target gene knockdown in HREC and treatment of IS-injected rats with inhibitors (targeting IS production or downstream regulators) were employed to elucidate the detailed mechanisms and identify therapeutic targets for DR.ResultsMetabolomics identified 172 significantly altered metabolites in the vitreous humor of diabetics, including the dysregulated tryptophan metabolite indoxyl sulfate (IS). IS was observed to breach the blood-retinal barrier and accumulate in the intraocular fluid of diabetic rats. Both in vivo and in vitro experiments indicated that elevated levels of IS induced endothelial apoptosis and disrupted cell junctions. RNA sequencing pinpointed prostaglandin E2 (PGE2) synthetase-cyclooxygenase 2 (COX-2) as a potential target of IS. Validation experiments demonstrated that IS enhanced COX-2 expression, which subsequently increased PGE2 secretion by promoting transcription factor EGR1 binding to COX-2 DNA following entry into cells via organic anion transporting polypeptides (OATP2B1). Furthermore, inhibition of COX-2 in vivo or silencing EGR1/OATP2B1 in HREC mitigated IS-induced microcapillary damage and the activation of COX-2/PGE2.ConclusionOur study demonstrated that indoxyl sulfate (IS), a uremic toxin originating from the gut microbiota product indole, increased significantly and contributed to retinal microvascular damage in diabetic retinopathy (DR). Mechanistically, IS impaired retinal microvascular integrity by inducing the expression of COX-2 and the production of PGE2. Consequently, targeting the gut microbiota or the PGE2 pathway may offer effective therapeutic strategies for the treatment of DR.Graphical

A Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for Simultaneous Estimation of Saxagliptin and Avanafil: Application to Pharmacokinetic Drug‐Drug Interaction in Type 2 Diabetic Rat Model

ABSTRACTErectile dysfunction is a common complication of type 2 diabetes. The combination of saxagliptin and avanafil can effectively manage both conditions in individuals with type 2 diabetes. However, evaluating the potential pharmacokinetic interactions for co‐administration of saxagliptin and avanafil is crucial. Here, we developed a sensitive bioanalytical method for simultaneously quantifying saxagliptin and avanafil in rat plasma using liquid chromatography hyphenated to triple quadrupole mass spectrometry. The chromatographic separation of saxagliptin, avanafil, and irbesartan (internal standard) was achieved on an Aquity BEH C18 column (100 × 2.1 mm, 1.7 µm), using 0.1% formic acid in water and acetonitrile as mobile phase with the gradient elution at a flow rate of 0.2 mL/min. Mass detection was carried out using selective reaction monitoring mode, with the product ions for saxagliptin, avanafil, and irbesartan being 180.2, 375.1, and 207.1 m/z, respectively. The developed liquid chromatography coupled to tandem mass spectrometry method was validated as per the US Food and Drug Administration guidelines in rat plasma. The validation findings confirmed the method's robustness and suitability for accurate quantification of saxagliptin and avanafil in rat plasma with the limit of quantification of 1 ng/mL for both the drugs and were linear in the range of 1–2000 ng/mL. The study found no significant pharmacokinetic interaction between saxagliptin and avanafil, suggesting they can be safely co‐administered to patients with type 2 diabetes.

Implications for Clinical Practice, Mechanisms, and Efficacy of Ageratum conyzoides Leaf Extracts in Streptozotocin-Induced Diabetes Rats: An Investigation into Their Antidiabetic, Hypolipidemic, and Antiatherogenic Activities

Ageratum conyzoides, a perennial herb native to tropical and subtropical regions, has been utilized in traditional medicine for centuries due to its diverse therapeutic properties. This review consolidates current research on the antidiabetic, hypolipidemic, and antiatherogenic effects of Ageratum conyzoides leaf extracts, specifically in streptozotocin-induced diabetic rat models. The review explores the plant’s potential mechanisms of action, including enhancement of insulin sensitivity, improvement of lipid profiles, and reduction of atherosclerotic plaque formation. Ageratum conyzoides extracts have demonstrated significant antidiabetic effects by lowering blood glucose levels, enhancing insulin secretion, and improving insulin sensitivity. They also exhibit hypolipidemic effects by reducing total cholesterol, LDL cholesterol, and triglycerides, while increasing HDL cholesterol. Additionally, these extracts show antiatherogenic properties by inhibiting plaque formation and reducing oxidative stress, thereby supporting cardiovascular health. The review examines the pharmacokinetics and bioavailability of Ageratum conyzoides bioactive compounds, emphasizing the need for further research to optimize their therapeutic potential. Comparative studies highlight its efficacy relative to other natural remedies and pharmaceuticals, noting its favorable safety profile. The review underscores the importance of integrating Ageratum conyzoides into both traditional and modern medicine practices and explores its role in dietary supplements and functional foods. Ongoing translational research and clinical trials are essential to validate the efficacy and safety of these extracts for broader clinical application. Keywords: Ageratum conyzoides, Leaf Extracts, Streptozotocin, Diabetes, Rats

Antidiabetic activity and Safety evaluation of Triticum aestivum (wheatgrass) extract in Alloxan-induced diabetic rats model.

Triticum aestivum (wheatgrasses) extract was studied for antidiabetic activity using alloxan-induced diabetes mellitus in rats. Triticum aestivum at 50, 100, and 200 mg/kg showed significant antidiabetic activity; it effected profound reductions in blood glucose over 28 days, especially the higher doses of 100 and 200 mg/kg, which were more effective than Glibenclamide. At 2000 mg/kg, the extract did not lower the blood glucose of normoglycemic rats- an indication of its safety and lack of hypoglycemic responses under non-diabetic conditions. It would appear that the antidiabetic activity of Triticum aestivum is through the protection and regeneration of beta cells that enhance insulin secretion, which in turn increases the utilization of glucose and normalizes carbohydrate, fat, and protein metabolism. This gradual lowering of blood glucose levels brought on by Triticum aestivum is clinically highly desired. The elicited antidepressant effect of Triticum aestivum was very likely due to its antioxidant effects and beta-cell regeneration activity. Thus, Triticum aestivum can meet the demand for a nontoxic, safe alternative to orthodox antidiabetic agents. Triticum aestivum, antidiabetic activity, alloxan-induced diabetes, insulin secretion, beta-cell regeneration, glucose metabolism, safety, and Glibenclamide.

Intake of herring oil, but not of anchovy oil, resulted in a lower serum cholesterol concentration in male Zucker Diabetic Sprague Dawley rats.

Patients with type 2 diabetes have increased risks for dyslipidaemia and subsequently for developing vascular complications. A recent meta-analysis found that cetoleic acid (C22:1n-11) rich fish oils resulted in lower cholesterol concentration in rodents. The aim was to investigate the effect of consuming fish oils with or without cetoleic acid on serum cholesterol concentration in diabetic rats and to elucidate any effects on cholesterol metabolism. Eighteen male Zucker Diabetic Sprague Dawley rats were fed diets containing herring oil (HERO) or anchovy oil (ANCO) or a control diet with soyabean oil for 5 weeks. The HERO diet contained 0·70 % cetoleic acid, with no cetoleic acid in the ANCO diet. The HERO and ANCO diets contained 0·35 and 0·37 wt% EPA + DHA, respectively. Data were analysed using one-way ANOVA. The serum total cholesterol concentration was 14 % lower in the HERO group compared with ANCO and Control groups (P = 0·023). The HERO group had a higher faecal excretion of bile acids (P = 0·0036), but the cholesterol production in the liver, the hepatic secretion of VLDL and the liver's capacity to take up cholesterol were similar to controls. The ANCO diet did not affect the serum cholesterol concentration, but the hepatic cholesterol biosynthesis, the clearance of lipoprotein cholesterol and the excretion of bile acids in faeces were higher than in the Control group. To conclude, consumption of herring oil, but not of anchovy oil, led to a lower cholesterol concentration in a type 2 diabetes rat model.

Molecular mechanisms of Buqing granule for the treatment of diabetic retinopathy: Network pharmacology analysis and experimental validation.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Its blindness rate is high; therefore, finding a reasonable and safe treatment plan to prevent and control DR is crucial. Currently, there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic effects. To investigate the effects of Buqing granule (BQKL) on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo experiments. This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions (PPI), identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and preliminarily validated the screened core targets by molecular docking. Furthermore, we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection, and administered the appropriate drugs for 12 weeks after the model was successfully induced. Body mass and fasting blood glucose and lipid levels were measured, and pathological changes in retinal tissue were detected by hematoxylin and eosin staining. ELISA was used to detect the oxidative stress index expression in serum and retinal tissue, and immunohistochemistry, real-time quantitative reverse transcription PCR, and western blotting were used to verify the changes in the expression of core targets. Six potential therapeutic targets of BQKL for DR treatment, including Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3, were screened using PPI. Enrichment analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR treatment. Molecular docking prediction indicated that BQKL stably bound to these core targets. In vivo experiments have shown that compared with those in the Control group, rats in the Model group had statistically significant (P < 0.05) severe retinal histopathological damage; elevated blood glucose, lipid, and malondialdehyde (MDA) levels; increased Caspase-3, c-Jun, and TP53 protein expression; and reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, ganglion cell number, AKT1, MAPK1, and MAPK3 protein expression. Compared with the Model group, BQKL group had reduced histopathological retinal damage and the expression of blood glucose and lipids, MDA level, Caspase-3, c-Jun and TP53 proteins were reduced, while the expression of SOD, GSH-Px level, the number of ganglion cells, AKT1, MAPK1, and MAPK3 proteins were elevated. These differences were statistically significant (P < 0.05). BQKL can delay DR onset and progression by attenuating oxidative stress and inflammatory responses and regulating Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3 proteins in the MAPK signaling pathway mediates these alterations.

10 kHz spinal cord stimulation improves metrics of spinal sensory processing in a male STZ rat model of diabetes

To explore why clinical 10 kHz spinal cord stimulation (10 kHz SCS) might improve neurological function in a model of painful diabetic neuropathy (PDN), the short-term behavioral, electrophysiological, and histological effects of 10 kHz SCS were studied using adult male streptozotocin (STZ)-induced diabetic Sprague-Dawley rats. Four testing groups were established: Naïve controls (N = 8), STZ controls (N = 7), STZ+Sham SCS (N = 9), and STZ+10 kHz SCS (N = 11). After intraperitoneal injection (60 mg/kg) of STZ caused the rats to become hyperglycemic, SCS electrodes were implanted in the dorsal epidural space over the L5-L6 spinal segments in the STZ+Sham SCS and STZ+10 kHz SCS groups and were stimulated for 14 days. The von Frey filament paw withdrawal threshold was measured weekly. At termination, animals were anesthetized and the electrophysiologic response of dorsal horn neurons (receptive field size, vibration, radiant warmth) of the ipsilateral foot was measured. Tissue from the plantar paw surface was obtained post-euthanization for intraepidermal nerve fiber density measurements. In comparison to other control groups, while no significant effect of 10 kHz SCS on peripheral intraepidermal nerve fiber density was observed, 10 kHz SCS ‘normalized’ the central neural response to vibration, receptive field, and paw withdrawal threshold, and elevated the neural response to tissue recovery from warm stimuli. These results suggest that short-term, low intensity 10 kHz SCS operates in the spinal cord to ameliorate compromised sensory processing, and may compensate for reduced peripheral sensory functionality from chronic hyperglycemia, thereby treating a broader spectrum of the sensory symptoms in diabetic neuropathy.

Semaglutide functional electrospinning nanofiber membrane rescues apoptosis and promotes diabetic wound healing

The healing of diabetic wounds is a difficult problem due to decreased proliferation, and migration of epidermal and endothelial cells. Here we reported semaglutide-loaded nanofiber membrane to promote diabetic wound healing through suppressing reactive oxygen species production and accelerating angiogenesis in a diabetic rat model. The fiber membrane was prepared by an electrostatic spinning technique. The fiber membrane consisted of thermalplastic polyurethane elastomer, polyvinyl butyral ester, zein and semaglutide (SMGT). The fiber membrane had a uniformly distributed diameter, suitable water vapor transmission rate, good water absorption and retention properties. In vivo data determined that the SMGT-loaded nanofiber membrane was able to promote normal skin pathological structure formation in regenerated tissue. In vitro experiments displayed that SMGT might facilitate HG-induced endothelial cell dysfunction by inhibiting ROS production. The present study provided a theoretical basis for the extensive application of SMGT in the treatment of diabetic ulcers and other wounds.

Utilization of Nanotechnology in Metformin Delivery: The Morphometric Study of Pancreatic Islets of Diabetic Rat Model

Utilization of Nanotechnology in Metformin Delivery: The Morphometric Study of Pancreatic Islets of Diabetic Rat Model

Ruxolitinib Has a Protective Effect on Ovarian and Endometrial Tissues in Diabetic Rats via STAT3 Pathway

Background: Hyperglycemia is associated with ovarian dysfunction. Advanced glycation end products (AGE) may affect ovarian function by binding to particular AGE receptors (RAGE). Hematopoiesis and immunological conditioning are both controlled by the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Many JAK-STAT signaling inhibitors, including ruxolitinib, have been approved to treat inflammatory disorders. We aimed to examine the potential protective effect of ruxolitinib, on ovarian dysfunction by comparing biochemical, pro-inflammatory, and histological abnormalities in a diabetic rat model. Methods: 24 female Wistar albino rats were included in the study. Diabetes was induced by streptozotocin (STZ) in 16 rats. Group 1: control (no diabetes mellitus, n = 8), Group 2 (diabetic = 8, 1 mL/kg/day saline, 4 weeks), and Group 3 (diabetic, n = 8, 2 mg/kg/day ruxolitinib, 4 weeks). The animals were euthanized, and bilateral hysterectomy and ovariectomy were performed for histopathological examination. The levels of signal transducer and activator of transcription 3 (STAT3) in tissue supernatants were measured. Results: Endometrial gland, ovarian stromal, and ovarian follicle degeneration scores were higher in group 2 compared with group 3 at p &lt; 0.001, whereas ovarian STAT3 level was significantly higher in group 2 compared with group 3 at p &lt; 0.001. Conclusions: Ruxolitinib can be a promising candidate for providing endometrial and ovarian structure continuity by JAK-STAT inhibition in diabetes.