Induction Of Diabetes Research Articles

Exploring the Therapeutic Efficacy of Ethanolic Extract of Benincasa hispida in Alloxan Induced Diabetic Rats

Since the dawn of civilization, humans have used herbal medicine to treat medical ailments. This study seeks to evaluate the efficacy of Benincasa hispida as an anti-diabetic agent and its impact on lipid profiles. We assessed the efficacy of the anti-diabetes medication using the alloxan-induced diabetic model. Only the 900 mg/kg dosage exhibited statistically significant antidiabetic effects (p < 0.05) when compared to the 300 and 600 mg/kg dosages. Notwithstanding a slight reduction in these parameters, no groups demonstrated statistically significant results regarding HDL, LDL, and total cholesterol. The triglyceride value of 97.70 ± 7.50* yielded statistically significant results (p < 0.05). Conversely, SGPT and SGOT exhibited no statistically significant effects at dosages of 300, 600, or 900 mg/kg. Group 5 exhibited statistically significant results (p < 0.05) in the kidney function test in case of urea, with a value of 93.24 ± 9.23* after the administration of an extract at a dose of 600 mg/kg. No statistically significant results were seen in any groups concerning creatinine levels.

Retinal OCT-Derived Texture Features as Potential Biomarkers for Early Diagnosis and Progression of Diabetic Retinopathy.

Diabetic retinopathy (DR) is usually diagnosed many years after diabetes onset. Indeed, an early diagnosis of DR remains a notable challenge, and, thus, developing novel approaches for earlier disease detection is of utmost importance. We aim to explore the potential of texture analysis of optical coherence tomography (OCT) retinal images in detecting retinal changes in streptozotocin (STZ)-induced diabetic animals at "silent" disease stages when early retinal molecular and cellular changes that cannot be clinically detectable are already occurring. Volume OCT scans and electroretinograms were acquired before and 1, 2, and 4 weeks after diabetes induction. Automated OCT image segmentation was performed, followed by retinal thickness and texture analysis. Blood-retinal barrier breakdown, glial reactivity, and neuroinflammation were also assessed. Type 1 diabetes induced significant early changes in several texture metrics. At week 4 of diabetes, autocorrelation, correlation, homogeneity, information measure of correlation II (IMCII), inverse difference moment normalized (IDN), inverse difference normalized (INN), and sum average texture metrics decreased in all retinal layers. Similar effects were observed for correlation, homogeneity, IMCII, IDN, and INN at week 2. Moreover, the values of those seven-texture metrics described above decreased throughout the disease progression. In diabetic animals, subtle retinal thinning and impaired retinal function were detected, as well as an increase in the number of Iba1-positive cells (microglia/macrophages) and a subtle decrease in the tight junction protein immunoreactivity, which did not induce any physiologically relevant effect on the blood-retinal barrier. The effects of diabetes on the retina can be spotted through retinal texture analysis in the early stages of the disease. Changes in retinal texture are concomitant with biological retinal changes, thus unlocking the potential of texture analysis for the early diagnosis of DR. However, this requires to be proven in clinical studies.

Dimethyl Fumarate Improves Detrusor Contractility in Streptozotocin-Induced Diabetic Rats

Aim: The present study aimed to investigate potential effect of dimethyl fumarate (DMF) on bladder dysfunction in streptozotocin (STZ)-induced diabetic rats. Material and Methods: Adult male Sprague Dawley rats were given a single intraperitoneal dose of streptozotocin (60 mg/kg) to induce diabetes. After eight weeks, diabetic and nondiabetic rats were orally treated with DMF (25 or 100 mg/kg/day) or vehicle for four weeks orally. At 12 week after diabetes induction, in vitro organ bath studies were performed on detrusor strips of each rat and the contractile responses to KCl and carbachol (CCh) of the strips were evaluated. Results: The maximal KCl (80 mM)- and CCh-induced contractile responses of detrusor strips significantly (p

Fecal microbiota transplantation as a potential therapeutic approach to improve impaired glucose tolerance via gut microbiota modulation in rat model.

To investigate the impact of diet-induced gut microbiota alterations on type 2 diabetes and assess the therapeutic potential of Fecal Microbiota Transplantation (FMT) in restoring a balanced gut microenvironment. To induce type 2 diabetes, rats were fed a high-sugar high-fat diet (HSFD) for 90 days. After diabetes induction, animals were divided into an HSFD control group, a metformin group (100mg/kg), and an FMT group (100mg/kg), receiving treatment for an additional 90 days. Fasting blood glucose levels, glucose tolerance, serum markers (HbA1C, free fatty acids, lipopolysaccharides, pro-inflammatory and anti-inflammatory cytokines), and gut microbiota profiles via cecal metagenome sequencing were analyzed post-treatment. FMT effectively restored gut microbiota composition to a profile similar to healthy controls, rebalancing the Firmicutes/Bacteroidetes ratio and increasing beneficial taxa, including Prevotella ruminicola, Akkermansia muciniphila, Roseburia, and Faecalibacterium prausnitzii. These microbial shifts corresponded with significant metabolic improvements: FMT reduced inflammatory markers (LPS and FFA), lowered HbA1c, and improved glucose tolerance. Enhanced gut barrier integrity observed in FMT-treated animals likely contributed to reduced endotoxemia and systemic inflammation, distinguishing FMT's metabolic effects from those of metformin. Notably, FMT addressed the dysbiosis associated with HSFD, promoting microbial resilience and mitigating the metabolic disruptions linked to type 2 diabetes. These findings underscore the potential of FMT as a targeted therapeutic approach to modulate gut microbiota composition and mitigate metabolic dysregulation induced by high sugar high fat diet.

Anti‐Hyperlipidemic, Antioxidant, Anti‐Inflammatory and Antidiabetic Effect of Brucine Against Streptozotocin‐Induced Diabetic Nephropathy in Rats

ABSTRACTAmong the diabetes‐related complications, diabetic nephropathy is the major complication and it leads to end‐stage renal failure. In the current investigation, we examined the protection of brucine, an alkaloid extracted from the seeds of Strychnos nux vomica plant widely used in traditional Chinese and Indian medicines against diabetic‐induced nephropathy. Male Wistar rats were divided into four groups: control, diabetic rats, diabetic‐induced + 40 mg/kg brucine‐treated rats, and diabetic‐induced + 25 mg/kg metformin‐treated rats. The 35 mg/kg streptozotocin (STZ) was injected into (i.p.) rats to induce diabetes, and then rats were post‐treated with brucine and metformin for 45 days. The food intake, weight gain, fasting blood glucose, HbA1C, insulin, and HOMA‐IR values were measured on initial and after completion of treatment to confirm the induction of diabetes by STZ and the antidiabetic effect of brucine. The rats were euthanized on 45th day, and kidney tissue was isolated to assess the nephroprotective effect of brucine. The antioxidant property of brucine was analyzed by measuring the oxidative stress and antioxidant biomarkers. The lipid profiles in the control and treated rats were measured. To assess the nephroprotective effect of brucine KIM‐1 protein was measured. The anti‐inflammatory property of brucine was assessed by quantifying the levels of pro‐inflammatory cytokines i.e., NF‐κB, TNF‐α, IL‐1β, IL‐6, TGF‐β and to confirm the nephroprotective effect. The histopathological analysis was also performed with H&E staining. Our results suggested that brucine showed potent antidiabetic, antioxidant, antilipidemic, anti‐inflammatory, and nephroprotective properties.

Propolis extract nanoparticles alleviate diabetes-induced reproductive dysfunction in male rats: antidiabetic, antioxidant, and steroidogenesis modulatory role.

Diabetes can affect male fertility via oxidative stress and endocrine system disruption. Nanomedicine based on natural products is employed to address diabetes complications. The current study aims to investigate the potential beneficial effect of propolis extract nanoparticles against diabetes-induced testicular damage in male rats. Sixty male rats were randomly allocated to six groups (n = 10). The first group served as a control group. The second and third received propolis extract (Pr)and propolis extract nanoparticles (PrNPs). The fourth group is the diabetic group that received streptozotocin (STZ) (55mg kg/bwt) single-dose i/p. The fifth and sixth groups are diabetic rats treated with Pr and PrNPs. Both Pr and PrNPs were received at a dose (100mg/kg bwt) orally. After 60 days, animals were euthanized, then pancreatic and testicular tissues were collected for redox status evaluation, gene expression analysis, and histopathological examination. Also, hormonal analysis (Insulin, total testosterone, and luteinizing hormone (LH) ) along with semen quality evaluation were done. Results showed that the induction of diabetes led to testicular and pancreatic redox status deterioration showing a reduction in reduced glutathione (GSH)as well as elevation of malondialdehyde (MDA), and nitric oxide (NO) levels. Also, relative transcript levels of testicular cytochrome P450 family 11 subfamily A member 1 (CYP11A1), 3β-Hydroxysteroid dehydrogenase (HSD-3β), and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) were significantly down-regulated, While the advanced glycation end-product receptor (AGER) relative gene expression was significantly upregulated. Furthermore, hormonal and semen analysis disturbances were observed. Upon treatment with Pr and PrNPs, a marked upregulation of testicular gene expression of CYP11A1, HSD-3β, and NFE2L2 as well as a downregulation of AGER, was observed. Hormones and semen analysis were improved. In addition, the testicular and pancreatic redox status was enhanced. Results were confirmed via histopathological investigations. PrNPs outperformed Pr in terms of steroidogenesis pathway improvement, testicular antioxidant defense mechanism augmentation, and prospective antidiabetic activity.

Hypolipidemic Effects of Eryngium Caucasicum Leaves Extract on Rats with Induced Diabetes Mellitus

Research Article AJVS. 2024; 17(2): 1-7doi: 10.37940/AJVS.2024.17.2.1 Hypolipidemic Effects of Eryngium Caucasicum Leaves Extract on Rats with Induced Diabetes Mellitus Glaucio Dire Feliciano. Abstract This research aimed to assess the hypolipidemic effects of an extract from Eryngium caucasicum in a Rat model of Type 2 Diabetes Mellitus produced by Streptozotocin. Forty adult male Wistar rats were divided into five groups, with a total of eight rats in each: (1) healthy control rats, (2) diabetic rats with no diabetes, (3) diabetic rats given insulin, (4) diabetic rats given 200 mg/kg orally for 30 days of Eryngium caucasicum extract, and (5) diabetic rats given 300 mg/kg orally for 30 days. Injecting Nicotinamide and Streptozotocin intraperitoneally caused diabetes. Fasting blood sugar, hepatic enzymes, and lipid profiles were determined from blood samples taken after the trial. The levels of HDL were increased significantly in G3, G4, and G5 compared to G2. The insulin group and the group given 300 mg/kg of Eryngium caucasicum substantially reduced LDL cholesterol compared to the G2. It should be mentioned that the diabetic control group had higher TC compared to the healthy control group after rat diabetes induction (P = 0.020). Compared to the G2, G3 treated with insulin and groups treated with extract at dosages of 200 as well as 300 mg/kg body weight had a substantially lower TC (P < 0.01). Serum TG was improved when insulin and Eryngium caucasicum extract were administered at 200 and 300 mg/kg dosages, respectively (P < 0.05). Serum ALT and AST levels were shown to be elevated after STZ diabetes induction as compared to the G1. Even though diabetic rats' ALT and AST levels were enhanced by insulin and all 2 plant trial dosages, 200 and 300 mg/kg. In summary, our findings suggest that the antidiabetic, hypolipidemic, and hepato-protective properties of Eryngium caucasicum, when administered to an animal model of Type 2 diabetes mellitus, may vary with dosage.

Design and synthesis of novel 3,7-dihydro-1H-purine-2,6-diones as DPP-4 inhibitors: An in silico, in vitro and in vivo approach.

The inhibition of enzyme DPP-4 is pivotal for targeting type 2 diabetes mellitus (DM). The study introduces two series of novel 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones derivatives (PB01-PB10) and 3,7-dihydro-1H-purine-2,6-diones compounds (PB11-PB16) were developed using linagliptin scaffold. Sixteen derivatives were synthesized and screened in vitro against DPP-4, revealing IC50 ranging from 15.66±2.546 to 28.45±4.441nM. Compounds PB01 and PB11 demonstrated high potency comparable to reference standard linagliptin (IC50=15.66±2.546, 16.16±1.214, 15.37±2.481nM, respectively). Further studies showed that the compound possesses negligible cytotoxicity up to 100μM concentration. A high glucose-induced DPP-4 upregulation model was further utilized to assess the protective effect of PB01 and PB11, and their efficacy was compared with linagliptin. PB01 and PB11 showed comparable protective effects against high glucose-induced ROS generation and mitochondrial superoxide production, and the compounds also effectively reduced the DPP-4 cellular expression. The in vivo anti-diabetic efficacy, effect on change in body weight, and OGTT due to PB01 and PB11 treatments were evaluated using the STZ-Nicotinamide-induced experimental model of diabetes in mice. Post induction of diabetes, the periodic estimation of blood serum glucose levels reveals that treatment with PB01 and PB11 decreased the high blood serum glucose levels in both acute and chronic studies. The expressions of DPP-4 were observed by IHC, Flowcytometry, and RT-qPCR. The docked complexes of both compounds, along with the standard drug linagliptin, were subjected to molecular dynamics simulation for 140ns to evaluate the complexes' stability and binding affinity.

Modulation of PPAR-γ/Nrf2 and AGE/RAGE signaling contributes to the chrysin cardioprotection against myocardial damage following ischemia/reperfusion in diabetic rats.

Advanced glycation end products/receptor for AGEs (AGE/RAGE) signaling has a well-established role in the etiology of diabetic-related cardiovascular disorders. The purpose of the study was to elucidate the role of chrysin, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, against ischemia/reperfusion (IR) injury in diabetic rats and its functional interaction with the AGE/RAGE signaling pathway. A single intraperitoneal injection of streptozotocin (STZ, 70mg/kg) was administered to rats for induction of diabetes. Rats having blood glucose levels more than 300mg/dl following a 72hr STZ injection were classified as diabetic. PPAR-γ antagonist GW9662 (1mg/kg, i.p.), chrysin (60mg/kg, p.o.), or both were administered to diabetic rats for 4 weeks. On the 29th day, rats were given ischemia for 45min and then reperfusion for 1hr to induce myocardial infarction (MI). Pretreatment with chrysin significantly improved hemodynamic status, ventricular functions, and cardiac injury markers in diabetic myocardium. Increased PPAR-γ/Nrf2 and decreased RAGE protein expressions were linked to this improvement. Chrysin pretreatment resulted in the upregulation of endogenous antioxidants and reduced TBARS levels. Moreover, chrysin significantly decreased inflammation and apoptosis in diabetic myocardium. PPAR-γ/Nrf2 co-activation by chrysin ameliorated IR-induced MI in diabetic rats, possibly via modulating AGE/RAGE signaling.

The effects of modest intake of soy milk enriched with Lactobacillus casei and omega-3 on the testis parameters in diabetic rats: a stereological study.

Diabetes mellitus is a widely distributed endocrine disorder in the world. Altered reproductive function is a notable long-term consequence of type 1 diabetes mellitus (T1DM). In the current study, we assessed the effects of soya milk containing Lactobacillus casei and omega-3 on stereology of testes in type 1 diabetic rats. 30 male Sprague Dawley rats were randomly allocated into five groups. Streptozocin (STZ (60 mg/kg)) was applied for diabetes induction. The non-diabetic and diabetic control groups were fed with 1 ml of distilled water. Three treatment diabetic groups were fed 1 ml of Soy milk group (SM), Probiotic soy milk group (PSM), and Omega-3 probiotic soy milk group (OPSM) via intragastric gavage for 60 days. At the endpoint, the animals were sacrificed and serum luteinizing hormone (LH), Follicle-stimulating hormone (FSH), testosterone, MDA besides testicular, and seminal parameters were analyzed. The administration of soy milk supplemented with L. casei and omega-3 in diabetic rats elevated the concentrations of LH, FSH, testosterone, and reduced malondialdehyde (MDA). In addition, this combination improved sperm quality, enhanced the number of sperm with rapid progress, increased testis weight and volume, seminiferous tubule and germinal epithelium volume; and also augmented the number of spermatogonia, spermatocyte, round and long spermatids, Sertoli cells and Leydig cells. Supplementation with soy milk containing L. casei and omega-3 can inhibit T1DM-induced infertility rats through improving testicular parameters, enhancing sperm quality, and increasing Sertoli and Leydig cell number.

Select Endocrine Disorders and Exosomes in Early PDAC Diagnosis.

Disturbances in carbohydrate metabolism are suggested to be the early symptoms of pancreatic ductal adenocarcinoma (PDAC). The accumulated data suggests that endocrine function-related biomarkers may represent a breakthrough in the early detection of PDAC. Factors which may predispose one to the development of PDAC are insulin resistance and hyperinsulinemia. Elevated insulin levels induce the onset of carcinogenesis by altering the differentiation and function of islet cells through stimulating growth factors, including insulin-like growth factors (IGFs). Impaired β cell function, along with the impact of PDAC-released factors (e.g., adrenomedullin (ADM), IGF-1, and macrophage inhibitory factor (MIF) on pancreatic islets, may contribute to the induction of diabetes associated with PDAC. Recently, exosomes have attracted worldwide attention due to their role in varied features of cell function, particularly in cancer progression. Exosomes comprise of small extracellular vesicles produced by almost all cells. These vesicles contain a vast array of biomolecules, including proteins and microRNAs. Exosomes participate in cancer growth and promote angiogenesis. They promote tumorigenesis and metastasis, and are associated with the acquisition of cancer cells resistant to chemotherapy. Data have been accumulating recently on the role of exosomes in the rapid recognition, prognosis and potential therapy of pancreatic cancer.

Effect of Different Rates of Rambutan Peel Extract on Visfatin and Cardiac Troponin I Response in Type 2 Diabetic Rats Induced with Streptozotocin

Background: The aim of this study was to investigate the effects of STZ (Streptozotocin) and Rambutan peel extract (RPE) on serum visfatin and cardiac response in experimental Type 2 diabetic rats. Methods: In this study, 64 adult male Wistar albino rats, aged between 8-10 weeks, were used. 8 groups were randomly selected, each containing 8 rats as Control (C), R100 (RPE 100 mg/kg group given with oral gavage route of administration (OGRA), R200 (RPE 200 mg/kg group given with OGRA), R300 (RPE 300 mg/kg group given with OGRA); Diabetes Control (DC): STZ 50 mg/kg i.p administered group, DR100 (D+100 mg/kg JPE), DR200 (D+200 mg/kg JPE), DR300 (D+300 mg/kg JPE). The study lasted a total of 31 days, including adaptation (7 days), induction of diabetes (3 days), and trial period (21 days). Blood samples were taken from the tail vein (vena caudalis) of all subjects on days 0 and 21 of the study. Visfatin and cTnI levels in the serum samples were measured and evaluated by ELISA method. Result: While the increase in mean serum visfatin and cTnI levels in diabetic groups was seen mostly in DC groups, the most significant decrease in mean serum visfatin level due to the addition of RPE was determined in DR100 groups (p less than 0.01).As a result, it was concluded that the administration of 100 mg/kg RPE in rats had no adverse effects. It was concluded that RPE, which has a cardioprotective effect by regulating the visfatin response that plays a role in the development of diabetes, may be useful in supporting the impaired cardiovascular system function that occurs in diabetes.

HISTOLOGICAL CHANGES IN THE RAT SPLEEN IN THE EARLY STAGES OF EXPERIMENTAL STREPTOZOTOCIN-INDUCED DIABE-TES MELLITUS

Diabetes is a systemic disorder that has a significant impact on a number of different organ systems within the body. Studying changes in the spleen in diabetic rats aids in understanding these changes and their effect on immune function. The objective of the study is to investigate the characteristics of morphological changes in the structural components of the spleen in the early stage of experimental diabetes.Results. Morphological changes in the spleen during the early stages of streptozotocin-induced experimental diabetes mellitus were observed. Diabetes was induced by a single intraperitoneal injection of streptozotocin. Histological examination of the spleen was conducted 14 and 28 days after diabetes induction. In healthy rats, the spleen exhibited a normal structure with a clear distinction between red and white pulp. Morphometric analysis showed that lymphoid nodules had a diameter of (445.92±12.6) μm and a marginal zone thickness of (76.22±5.12) μm. After 14 days of experimental diabetes, histological preparations revealed reduced lymphoid nodules of white pulp with a diameter of (435.83±14.28) μm and germinal centers (139.97±5.74) μm. After 28 days, lymphoid nodules further decreased to (392.37±10.29) μm, and germinal centers - to (125.93±5.71) μm. The width of the periarterial lymphoid sheaths decreased to (67.91±3.62) μm, indicating early changes in T-cell zones.Conclusion. During the initial stages of diabetes mellitus in experimental settings, notable structural modifications occur in the spleen. Specifically, there is a reduction in the size of lymphoid nodules, germinal centers, and various zones of the spleen, as well as a decrease in the density of lymphocytes. These alterations may suggest a severe immunological dysfunction in rats used for experimentation.

Angiotensin-Converting Enzyme-Dependent Intrarenal Angiotensin II Contributes to CTP: Phosphoethanolamine Cytidylyltransferase Downregulation, Mitochondrial Membranous Disruption, and Reactive Oxygen Species Overgeneration in Diabetic Tubulopathy.

Aims: The limited therapeutic options for diabetic tubulopathy (DT) in early diabetic kidney disease (DKD) reflect the difficulty of targeting renal tubular compartment. While renin-angiotensin-aldosterone system (RAS) inhibitors are commonly utilized in the management of DKD, how intrarenal RAS contributes to diabetic tubular injury is not fully understood. Mitochondrial disruption and reactive oxygen species (ROS) overgeneration have been involved in diabetic tubular injury. Herein, we aim to test the hypothesis that angiotensin-converting enzyme (ACE)-dependent intrarenal angiotensin II (AngII) disrupts tubular mitochondrial membranous homeostasis and causes excessive ROS generation in DT. Results: Mice suffered from renal tubular mitochondrial disruption and ROS overgeneration following high-fat diet/streptozocin-type 2 diabetic induction. Intrarenal AngII generation is ACE-dependent in DT. Local AngII accumulation in renal tissues was achieved by intrarenal artery injection. ACE-dependent intrarenal AngII-treated mice exhibit markedly elevated levels of makers of tubular injury. CTP: Phosphoethanolamine cytidylyltransferase (PCYT2), the primary regulatory enzyme for the biosynthesis of phosphatidylethanolamine, was enriched in renal tubules according to single-cell RNA sequencing. ACE-dependent intrarenal AngII-induced tubular membranous disruption, ROS overgeneration, and PCYT2 downregulation. The diabetic ambiance deteriorated the detrimental effect of ACE-dependent intrarenal AngII on renal tubules. Captopril, the ACE inhibitor (ACEI), showed efficiency in partially ameliorating ACE-dependent intrarenal AngII-induced tubular deterioration pre- and post-diabetic induction. Innovation and Conclusion: This study uncovers a critical role of ACE-dependent intrarenal AngII in mitochondrial membranous disruption, ROS overgeneration, and PCYT2 deficiency in diabetic renal tubules, providing novel insight into DT pathogenesis and ACEI-combined therapeutic targets. Antioxid. Redox Signal. 00, 000-000.

Antidiabetic, Antihyperlipidemic and Protective Effect of Cupressus sempervirens L. Leaves Extract in Streptozotocin Induced Diabetic Rats

Antidiabetic, Antihyperlipidemic and Protective Effect of Cupressus sempervirens L. Leaves Extract in Streptozotocin Induced Diabetic Rats

Enhancing Wound Healing via Modulation of Autophagy-Induced Apoptosis: The Role of Nicotinamide Riboside and Resveratrol in Streptozotocin-Treated Diabetic Rat

BackgroundImpaired wound healing from diabetes mellitus (DM) causes lower limb amputations, posing clinical, social, and economic issues. Hypoxia and advanced glycation end products cause autophagy and apoptosis dysregulation, which delays wound healing. The study will test systemic and topical Nicotinamide Riboside (NR) and Resveratrol (RSV) for the capacity to modulate autophagy and apoptosis via the SIRT-1-FOXO1 pathway and improve diabetic wound healing. Methods54 male Sprague-Dawley rats were separated into control, diabetic (T1D), T1D-Gel-Base, T1D-NR, T1D-RSV, and T1D-NR+RSV groups. Rats were gavaged with 50 mg/kg/day RSV and 300 mg/kg/day NR for 5 weeks before having their wounds topically treated with 5% NR and RSV gel for 15 days after diabetes induction. Biochemical, histomorphometric, and stereological assays were conducted. The mRNA expressions of SIRT-1, FOXO1, VEGF, BAX, Cas3, Bcl-2, Beclin1, LC3IIβ, P62, and ATG5 were examined by qRT-PCR. ResultsNR and RSV improved diabetic rat wound closure. Diabetic rats treated with NR and RSV had significantly higher LC3IIβ, VEGEF, Bcl-2, and SIRT-1 mRNA levels. Bcl-2, p62, and ATG5 were regulated whereas BAX and Cas 3 were reduced. Stereological investigations showed epidermal, dermal, collagen bundle, vascular, and fibroblast density enhancements. ConclusionThis study highlights the potential of NR and RSV, acting as SIRT-1 activators, in improving diabetic wound healing by regulating SIRT-1-FOXO1-mediated autophagy and apoptosis. These findings offer valuable insights for developing targeted strategies to enhance diabetic wound healing. The combination of NR and RSV showed promising effects, suggesting a potential therapeutic approach for improving diabetic wound healing.

Efficient and Safe Induction of Diabetes in Experimental Animals: A Review on Alternative Models and Techniques

Diabetes Mellitus (DM) is a multitudinous metabolic disorder that can occur due to insufficient or inefficient levels of insulin that leads to hyperglycemia. In many conditions, diabetes can also directly or indirectly lead to other functional disorders such as dyslipidemia and hypertension making them more severe and life-threatening. It is believed that Type 1 Diabetes can be caused by to process of auto-immune destruction of beta-cells of Islet of Langerhans of the pancreas responsible for the production of insulin whereas Type 2 diabetes is because of resistance against insulin along with the futilities of beta-cells to compensate the body with the required amount of insulin. The animal models are considered an essential component in the experimental studies and drug discovery process. Animal models provide safety, effectiveness, and dose of the test substance that needs to be extrapolated to human use. There are several methods for the induction of diabetes in experimental animal models. The present review aimed to discuss and explore currently used approaches including models from streptozotocin-induced diabetes to transgenic models for reproducible and safe diabetes induction in different experimental animals (rats, mice, guinea pigs, and dogs) and sex. Additionally, some genetically modified animal models are also included and discussed in this review which will pave the way for further studies.

Polyphenol-rich Ocimum gratissimum leaf extract attenuates angiotensin-converting enzyme activity and impaired endothelial vascular function in diabetic rats

Endothelial vascular dysfunctions are prevalent among diabetic patients, significantly impacting their quality of life and prognosis. This study examined the effects of polyphenol-rich extracts from Ocimum gratissimum leaves on oxidative stress markers, serum lipid profiles, and angiotensin-converting enzyme activity in diabetic cardiac tissue. Forty Wistar rats (150–220 g) were divided into five groups: normal control, diabetic control, low-dose Ocimum gratissimum (122.46 mg/kg), medium-dose Ocimum gratissimum (244.98 mg/kg), and a positive control (standard diabetic drug). All rats except the normal control group were made diabetic via an intraperitoneal injection of 50 mg/kg streptozotocin, followed by 28 days of extract administration. Diabetes induction led to a significant (p<0.05) disruptions in lipid profiles, oxidative stress markers, and ACE activity. Treatment with Ocimum gratissimum extracts at both doses significantly (p<0.05) decreased triglyceride, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol. Lipid peroxidation marker, malondialdehyde, was significantly (p<0.05) decreased, and antioxidant enzyme activities significantly (p<0.005) improved. ACE activity was significantly (p<0.05) reduced, approaching control levels. These results suggest that the polyphenol-rich extract of Ocimum gratissimum exerts antioxidant and cardio-protective effects, improving vascular functions in diabetic rats by improving lipid profiles, reducing oxidative stress, and suppressing ACE activity.

The Induction of Diabetes by High-Sugar and High-Fat Diets and Potential Applications of Healthy Eating

The rising prevalence of diabetes has intensified research in this field. Among the various causes of diabetes, insulin resistance plays a crucial role. High-sugar, high-fat diets are known to induce hyperglycemia and obesity, which significantly affect the progression of insulin resistance. It should be noted that obesity can significantly increase insulin resistance, thereby inducing prediabetes and aggravating diabetic symptoms. Additionally, such diets disturb the balance of intestinal flora. Controlling carbohydrate intake through low-carb or ketogenic diets can effectively improve glucose and lipid metabolism, improving insulin sensitivity, reducing insulin resistance, and lowering insulin levels. Adjustments to diet can also help shape a healthy gut flora composition. Furthermore, consuming natural products like flavonoids can also contribute to the improvement of diabetic symptoms. This article summarizes the impact of high-sugar, high-fat diets on the progression of diabetes, their effects on insulin resistance and intestinal flora, and the regulatory benefits of a healthy diet in managing diabetes.

New Insights on the potential therapeutic effects of glibenclamide and Obeticholic acid against Alloxan-Induced diabetes mellitus in rat model

Diabetes mellitus (DM) represents a highly prevalent metabolic disorder across the globe. This study aimed to determine the ameliorative efficacy of glibenclamide (Gli) and obeticholic acid (OCA) against biochemical and pathological changes related to alloxan-induced diabetes. Twenty male Wistar rats were allocated into four groups; Control group, Diabetic group: received intraperitoneal injection of alloxan (120 mg/kg) for induction of diabetes, Diabetic + Gli group: Diabetic rats treated daily with oral Gli (5 mg/kg) and Diabetic + OCA group: Diabetic rats treated daily with oral OCA (10 mg/kg). All rats were subjected to 30 days treatments. Our results indicated that Gli successfully ameliorated hyperglycemia and dyslipidemia with a significant decline in serum pancreatic lipase activity and increased insulin level, while OCA had the same effect but without any enhancement in serum insulin levels. Additionally, the disturbances in liver function-related parameters and the evoked oxidative stress, interleukin(IL)-6 and IL-10 in the liver and pancreas were abrogated upon treatment with Gli and OCA. Furthermore, Gli and OCA increased AMP-activated protein kinase (P-AMPK), insulin receptor substrate 1 (IRS1), farnesoid X receptor (FXR), and glucagon-like peptide-1 receptor (GLP-1R) expressions and downregulated sterol regulatory element binding protein-1c mRNA expression. Besides, Gli and OCA have alleviated diabetes-induced histopathological distortions in hepatic and pancreatic tissues and enhanced the immunoexpression of insulin, and proliferating cell nuclear antigen with decreased immune reactivity of glucagon within pancreatic tissues. Gli and OCA decreased the immune reactivity of nuclear factor kappa B and increased the glycogen content of hepatic tissues. In conclusion, OCA is efficacious in the management of dyslipidemia and hyperglycemia of DM and its related oxidative stress.