Experimental Models Of Diabetes Research Articles

Affective and Cognitive Impairments in Rodent Models of Diabetes.

Diabetes and related acute and long-term complications have a profound impact on cognitive, emotional, and social behavior, suggesting that the central nervous system (CNS) is a crucial substrate for diabetic complications. When anxiety, depression, and cognitive deficits occur in diabetic patients, the symptoms and complications related to the disease worsen, contributing to lower quality of life while increasing health care costs and mortality. Experimental models of diabetes in rodents are a fundamental and valuable tool for improving our understanding of the mechanisms underlying the close and reciprocal link between diabetes and CNS alterations, including the development of affective and cognitive disorders. Such models must reproduce the different components of this pathological condition in humans and, therefore, must be associated with affective and cognitive behavioral alterations. Beyond tight glycemic control, there are currently no specific therapies for neuropsychiatric comorbidities associated with diabetes; animal models are, therefore, essential for the development of adequate therapies. To our knowledge, there is currently no review article that summarizes changes in affective and cognitive behavior in the most common models of diabetes in rodents. Therefore, in this review, we have reported the main evidence on the alterations of affective and cognitive behavior in the different models of diabetes in rodents, the main mechanisms underlying these comorbidities, and the applicable therapeutic strategy.

Investigation of the relationship between plasma ghrelin levels and muscle atrophy in experimental diabetic rats

In this study, the relationship between plasma ghrelin levels and muscle atrophy was examined in an experimental diabetic rat model. 56 male Wistar albino rats, aged 8-10 weeks, were used in the study. The rats were divided into 8 groupsD1: one-week diabetes, C1: one-week control, D2: three-week diabetes, C2: three-week control, D3: six-week diabetes, C3: six-week control, D4: eight-week diabetes, C4: eight-week control. To induce diabetes, rats were injected with a single intraperitoneal dose of 45 mg/kg streptozotocin. At the end of the experiments, body weights and fasting blood sugar levels were measured. mTOR and myostatin levels of gastrocnemius muscle and plasma ghrelin levels were measured by ELISA method. Gastrocnemius muscle weight, cross-sectional area and histopathological images were examined. It was observed that the gastrocnemius weights of the D2, D3, D4 groups decreased significantly compared to their controls (p≤0.01). Muscle cross-sectional area decreased significantly in groups D3 and D4 compared to controls (p≤0.01). Muscle mTOR levels were found to be significantly lower in all diabetic groups compared to controls (p≤0.01). Although muscle myostatin levels were higher in the diabetic groups, this increase was only significant in the D4 group. Plasma ghrelin levels were significantly lower in all diabetic groups compared to controls (p≤0.01). A positive correlation was determined between plasma ghrelin levels and the final weights, muscle cross-sectional area, gastrocnemius weights and mTOR levels of the rats. Time-dependent muscle atrophy developed in diabetic rats and there was a relationship between muscle atrophy and plasma ghrelin level. We suggest that ghrelin plays a role in diabetes-induced muscle atrophy as well as cachexia and sarcopenia.

Antioxidative and Anti-inflammatory Effects of Plant-derived Hypoglycemic Medicines: An In vivo/In vitro Systematic Review.

The activation of oxidative stress and inflammatory conditions has been associated with acceleration in diabetes (DM) onset and complications. Despite various anti-DM medications, there is a growing trend to discover inexpensive and effective treatments with low adverse effects from plants as one of the promising sources for drug development. This study aimed to systematically investigate the simultaneous anti-inflammatory and antioxidant effects of plant-derived hypoglycemic medicines in diabetic experimental models. The search terms consisted of "diabetes", "herbal medicine", "antioxidant", "Inflammatory biomarker", and their equivalents among PubMed, Scopus, Web of Science, and Cochrane Library databases up to 17 August 2021. Throughout the search of databases, 201 eligible experimental studies were recorded. The results showed that the most commonly assessed inflammatory and oxidative stress biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL) 6, IL-1β, IL-10, malondialdehyde (MDA), and nitric oxide (NO). The activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were assessed in the present review. Among herbal treatments, Trigonella foenum-graecum L., Centella asiatica (L.) Urb., Vitis vinifera L., and Moringa oleifera Lam. were most commonly used for diabetic complications. Due to the dispersion of the treatments, meta-analysis was not applicable. Our findings showed that the application of different plant-derived hypoglycemic treatments in animal models improved diabetes and its complications, as well as modulated concomitant inflammatory and oxidative stress biomarkers. These findings suggest that plant-based antidiabetic medicines and food supplements have the potential to manage diabetes and its complications.

The interaction of choline and one-carbon / folate metabolism derangements on the cardiac remodeling process with or without diabetes

Proper nutrition helps protect from illness and disease. Choline (Ch), an essential molecule of substantial importance for the optimal development and function of several biological systems, plays a crucial role in the pathway of one-carbon metabolism. On the other hand, Ch-deprivation (CD) has been linked with abnormal fat metabolism, insulin resistance, and myocardial dysfunction. The Ch-deficiency setting is an established experimental model of non-alco¬holic steatohepatitis that resembles the human non-alcoholic fatty liver disease (NAFLD); a disease with constantly increasing incidence and prevalence. NAFLD, commonly associated with metabolic comorbidities such as obesity and type 2 diabetes mellitus, consists a high risk for cardiovascular disease. Experimental data of dietary CD through the administration of a Ch-deficient diet to rodents have revealed myocardial monocyte infiltration along with cardiac interstitial oedema and fibrosis, as well as a deleterious effect on cardiac valves that could lead to impaired heart mechanical properties which resemble to a restrictive pattern of cardiomyopathy characterised mainly by diastolic dysfunction. In a Ch-deprived diabetic experimental model, the diastolic heart failure has been characterized by a concentric hypertrophied myocardium, a left ventricular cavity with a thinner wall, and an increased left ventricular diastolic diameter, in addition to a left atrial dilatation that could also exert functional derangement and provoke arrhythmogenesis, thereby jeopardising cardiac output.

Piperine Regulates Inflammatory Signalling Molecules in Adipose Tissue: A High Fat Diet Sucrose Induced Type II Diabetic Experimental Model

Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. An extract of the active phenolic component of black pepper (Piper nigrum), piperine, is well known to provide beneficial physiological effects. This study aims to assess the regulation of inflammatory signalling molecules in adipose tissue by Piperine using a high diet and sucrose-induced type II diabetic experimental model. Our results suggest that piperine has the potential as a therapeutic drug or dietary supplement.

The effect of Hydroxytyrosol on Spexin immunoreactivity in pancreatic islets and serum insulin levels in a Streptozotocin-induced experimental diabetes model in rats

Diabetes (DM), a major health problem worldwide, is associated with the loss of β cells in the pancreatic islets and decreased insulin secretion. Hydroxytyrosol (HxT) is a phenol found in high concentrations in olive oil. Spexin (SPX) plays a role in regulating many metabolisms such as glucose and energy. This study aimed to determine the effects of HxT on circulating insulin levels, histopathological changes in pancreatic islets, and SPX immunoreactivity in a Streptozotocin-induced experimental diabetes model (eDM) in rats. The 32 male rats used in the study were randomly divided into 4 groups (n: 8): Control, eDM, eDM+HxT, and HxT. After completing all applications in the experiment, the blood and pancreas tissues of the sacrificed rats were taken. Insulin levels were determined from the serum samples obtained. Histopathological changes and SPX immunoreactivities were evaluated in pancreatic tissues. While serum insulin levels decreased in eDM, histopathological changes in pancreatic islets increased. Additionally, SPX immunoreactivity in pancreatic islets was significantly reduced in eDM. On the other hand, HxT supplementation (eDM+HxT group) regulated eDM-related adverse effects. While HxT supplementation may have a curative and therapeutic effect in DM, it was concluded that SPX may be effective in regulating the endocrine functions of the pancreas.

Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy

BackgroundDiabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators.MethodsA male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators.ResultsSaline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1β) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks.ConclusionIntravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators.

In vitro and in vivo evaluation of isoxsuprine loaded invasomes for efficient treatment of diabetes‐accelerated atherosclerosis

Hyperglycemia in diabetes mellitus exacerbates vascular disarray in atherosclerosis by damaging endothelial cells and vascular smooth muscles. It's a major contributor to deaths from cardiovascular disease. Isoxsuprine (IXS) is an oral beta-adrenergic agonist that improves arterial blood flow due to its vasodilatation effect and boosts insulin secretion. However, oral IXS has low efficacy, low bioavailability and patient incompliance due to its high dose frequency, short biological half-life and fast clearance. The goal of this research was to develop a nasal formulation of IXS-loaded invasomes to sustain IXS's release and improve its permeation and efficacy as a potential diabetes-accelerated atherosclerosis treatment. Different IXS-loaded invasomes formulations were developed using design expert software to study the effects of ethanol, phospholipid, and cineole concentrations. Based on the desirability index, the formulation with 1 % ethanol, 0.5 % cineole, and 2.48 % phospholipid was chosen as the optimum formulation. The optimum IXS-loaded invasomes formulation showed an encapsulation efficiency of 72.03 % and a particle size of 210.26 nm. Production of nasal IXS-loaded invasomes formulation increased the permeation of IXS with a ratio of 2.25 and sustained its release. The optimum IXS-loaded invasomes formulation was non-cytotoxic and showed a good binding mode with serum proteins. When optimum IXS-loaded invasomes formulation was evaluated in vivo against a rat model of experimental diabetes and atherosclerosis, it showed anti-diabetic and anti-atherosclerotic effects. It substantially increased the levels of HDL by 45.11 % and substantially decreased the levels of glucose, LDL, triglycerides, and cholesterol by 41.35 %, 89.76 %, 51.01 %, and 60.18 %, respectively. Histopathology also showed that atherosclerotic lesions got improved in rats given optimum IXS-loaded invasomes formulation. In conclusion, nasal administration of IXS-loaded invasomes could be a potential diabetes-accelerated atherosclerosis treatment.

Comparative Screening of the Liver Gene Expression Profiles from Type 1 and Type 2 Diabetes Rat Models.

Experimental animal models of diabetes can be useful for identifying novel targets related to disease, for understanding its physiopathology, and for evaluating emerging antidiabetic treatments. This study aimed to characterize two rat diabetes models: HFD + STZ, a high-fat diet (60% fat) combined with streptozotocin administration (STZ, 35 mg/kg BW), and a model with a single STZ dose (65 mg/kg BW) in comparison with healthy rats. HFD + STZ- induced animals demonstrated a stable hyperglycemia range (350-450 mg/dL), whereas in the STZ-induced rats, we found glucose concentration values with a greater dispersion, ranging from 270 to 510 mg/dL. Moreover, in the HFD + STZ group, the AUC value of the insulin tolerance test (ITT) was found to be remarkably augmented by 6.2-fold higher than in healthy animals (33,687.0 ± 1705.7 mg/dL/min vs. 5469.0 ± 267.6, respectively), indicating insulin resistance (IR). In contrast, a more moderate AUC value was observed in the STZ group (19,059.0 ± 3037.4 mg/dL/min) resulting in a value 2.5-fold higher than the average exhibited by the control group. After microarray experiments on liver tissue from all animals, we analyzed genes exhibiting a fold change value in gene expression <-2 or >2 (p-value <0.05). We found 27,686 differentially expressed genes (DEG), identified the top 10 DEGs and detected 849 coding genes that exhibited opposite expression patterns between both diabetes models (491 upregulated genes in the STZ model and 358 upregulated genes in HFD + STZ animals). Finally, we performed an enrichment analysis of the 849 selected genes. Whereas in the STZ model we found cellular pathways related to lipid biosynthesis and metabolism, in the HFD + STZ model we identified pathways related to immunometabolism. Some phenotypic differences observed in the models could be explained by transcriptomic results; however, further studies are needed to corroborate these findings. Our data confirm that the STZ and the HFD + STZ models are reliable experimental models for human T1D and T2D, respectively. These results also provide insight into alterations in the expression of specific liver genes and could be utilized in future studies focusing on diabetes complications associated with impaired liver function.

Polygonatum sibiricum (Huang Jing) polysaccharide reduces diabetic cardiomyopathy through increasing cyclic guanosine monophosphate-protein kinase G signaling in diabetic mice.

Diabetic cardiomyopathy (DCM) is a prevalent condition among individuals with diabetes, and is associated with a high mortality rate. The anti-oxidant properties of Jing Huang or Polygonatum sibiricum polysaccharide (PSP) have been extensively used to treat diabetes-related disorders; however, its potential effectiveness against DCM remains unknown. This study aimed to investigate PSP's therapeutic effects on DCM in an experimental diabetic mouse model. To induce insulin resistance, mice were fed a high-fat diet for 3 months, followed by intraperitoneal streptozotocin injection to induce slight hyperglycemia and develop DCM. Both DCM and control mice were given PSP orally for 3 weeks. Western blotting was used to detect the protein expressions of protein kinase G, C/EBP homologous protein, glucose-regulated protein 78, phosphodiesterase type 5, protein kinase R-like endoplasmic reticulum (ER) kinase, and phospho-protein kinase R-like endoplasmic reticulum kinase in heart tissue. The results showed a reduction in bodyweight and blood glucose levels in the PSP therapy group compared with DCM group. PSP also improved cardiac function and had a negligible effect on malondialdehyde activity. Furthermore, the findings showed that PSP alleviated ER and oxidative stress observed in DCM mice hearts, leading to the inhibition of cyclic guanosine monophosphate-specific phosphodiesterase type 5 and cardiac cyclic guanosine monophosphate reactivation. Phosphodiesterase type 5 inhibition reduced high-fat diet-induced cardiac dysfunction and decreased ER stress. PSP could effectively protect diabetic myocardium by inhibiting endoplasmic reticulum stress. These findings provide crucial insights into the potential of PSP to ameliorate DCM conditions in diabetic mice by decreasing ER and oxidative stress, and enhancing cyclic guanosine monophosphate protein kinase G signaling.

Association of serum NF-κB levels with peripheral neuropathy in type 2 diabetes mellitus patients: a pilot study.

Hyperglycaemia-induced inflammation plays a vital role in the development of diabetic peripheral neuropathy (DPN). Recent evidences had reported the involvement of the transcription factor nuclear factor kappa-light-chain-enhancer of activated Bcell (NF-κB) in diabetic experimental models. So, this pilot study aimed to evaluate serum NF-κB levels in DPN patients. We recruited 50 T2DM patients, of which 25 were T2DM with neuropathy and 25 were T2DM without neuropathy. In all the participants peripheral neuropathy was diagnosed based on Total neuropathy score (TNS). Serum NF-κB levels were measured by ELISA. We observed that the serum NF-κB levels were higher in DPN patients in comparison to T2DM patients without neuropathy. On spearman correlation, a positive correlation was found between serum NF-κB levels and TNS in the DPN group (r=0.741, p<0.001). The regression model shows the TNS to be an independent determinant of serum NF-κB levels after adjustment for potential confounders like age, duration of diabetes, and HbA1C (B=81.34; p<0.001). NF-κB activation plays a key role in promoting inflammation which is associated with the progression of DPN. In this respect, the study of NF-κB levels in serum may be an additional diagnostic marker for DPN.

Atlas of cardiac endothelial cell enhancer elements linking the mineralocorticoid receptor to pathological gene expression.

Endothelial cells play crucial roles in physiology and are increasingly recognized as therapeutic targets in cardiovascular disease. Here, we analyzed the regulatory landscape of cardiac endothelial cells by assessing chromatin accessibility, histone modifications, and 3D chromatin organization and confirmed the functional relevance of enhancer-promoter interactions by CRISPRi-mediated enhancer silencing. We used this dataset to explore mechanisms of transcriptional regulation in cardiovascular disease and compared six different experimental models of heart failure, hypertension, or diabetes. Enhancers that regulate gene expression in diseased endothelial cells were enriched with binding sites for a distinct set of transcription factors, including the mineralocorticoid receptor (MR), a known drug target in heart failure and hypertension. For proof of concept, we applied endothelial cell-specific MR deletion in mice to confirm MR-dependent gene expression and predicted direct MR target genes. Overall, we have compiled here a comprehensive atlas of cardiac endothelial cell enhancer elements that provides insight into the role of transcription factors in cardiovascular disease.

Propolis of Tubuna bee (Scaptotrigona bipunctata) from the Meliponini tribe alleviates glycaemic, oxidative, and inflammatory conditions during STZ induced diabetes in Wistar rats also aiding in injury recovery

This study was designed to characterize and describe the in vivo effects of an ethanolic propolis extract (EHAP) from the native Brazilian bee Tubuna (Scaptotrigona bipunctata). Propolis has been recently proposed as an adjuvant during diabetes, mainly because propolis possesses various natural compounds without the elevated sugar quantities found in pure honey. Compounds with biological activity and in vitro antioxidant potential have been detected in propolis from Tubuna. Streptozotocin (STZ) is a well-documented model to induce experimental diabetes in rodents. We have detected potential compounds in Tubuna propolis and observed the effects of daily oral treatment with EHAP in Wistar rats during experimental diabetes. EHAP improved glucose tolerance in STZ animals without significantly changing net and organ weight. STZ increases levels of TBARS and Carbonyl, and reduces levels of -SH, effects partially controlled by EHAP, particularly in serum. EHAP decreases inflammatory mediators TnF-ɑ and IL-1β in diabetic animals and decreases paw swelling during carrageenan induced edema. In conclusion, Tubuna propolis constituents possess interesting biological activities to aid in several diseases, but this still needs further studies in these particular pathologies. This is the first work to characterize Tubuna propolis from Rio Grande do Sul and the first work to describe its effects in an animal model of experimental diabetes or any animal model of disease. Treatment with EHAP shows potential to regulate conditions during STZ induced diabetes, aiding in injury recovery paw edema. Mechanistic studies, other models of long-term diabetes or metabolic syndrome, and a complete characterization of propolis from Tubuna are potential targets for future studies.

Comparative effects of pravastatin and rosuvastatin on carbohydrate metabolism in an experimental diabetic rat model.

Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg-1 day-1 doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg-1 day-1 reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg-1 day-1, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg-1 day-1, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg-1 day-1, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg-1 day-1 dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg-1 day-1 is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.

Afriplex GRTTM extract attenuates hepatic steatosis in an in vitro model of NAFLD.

Currently, it is acknowledged that vitamin E, insulin sensitizers and anti-diabetic drugs are used to manage non-alcoholic fatty liver disease (NAFLD), however, these therapeutic interventions harbour adverse side effects. Pioglitazone, an anti-diabetic drug, is currently the most effective therapy to manage NAFLD. The use of natural medicines is widely embraced due to the lack of evidence of their negative side effects. Rooibos has been previously shown to decrease inflammation and oxidative stress in experimental models of diabetes, however, this is yet to be explored in a setting of NAFLD. This study was aimed at investigating the effects of an aspalathin-rich green rooibos extract (Afriplex GRTTM) against markers of hepatic oxidative stress, inflammation and apoptosis in an in vitro model of NAFLD. Oleic acid [1 mM] was used to induce hepatic steatosis in C3A liver cells. Thereafter, the therapeutic effect of Afriplex GRTTM, with or without pioglitazone, was determined by assessing its impact on cell viability, changes in mitochondrial membrane potential, intracellular lipid accumulation and the expression of genes and proteins (ChREBP, SREBF1, FASN, IRS1, SOD2, Caspase-3, GSTZ1, IRS1 and TNF-α) that are associated with the development of NAFLD. Key findings showed that Afriplex GRTTM added to the medium alone or combined with pioglitazone, could effectively block hepatic lipid accumulation without inducing cytotoxicity in C3A liver cells exposed oleic acid. This positive outcome was consistent with effective regulation of genes involved in insulin signaling, as well as carbohydrate and lipid metabolism (IRS1, SREBF1 and ChREBP). Interestingly, in addition to reducing protein levels of an inflammatory marker (TNF-α), the Afriplex GRTTM could ameliorate oleic acid-induced hepatic steatotic damage by decreasing the protein expression of oxidative stress and apoptosis related markers such as GSTZ1 and caspase-3. Afriplex GRTTM reduced hepatic steatosis in oleic acid induced C3A liver cells by modulating SREBF1, ChREBP and IRS-1 gene expression. The extract may also play a role in alleviating inflammation by reducing TNF-α expression, suggesting that additional experiments are required for its development as a suitable therapeutic option against NAFLD. Importantly, further research is needed to explore its antioxidant role in this model.

1-Deoxynojirimycin Mitigates Glycogen and Carbohydrate Metabolic Enzyme Alterations in High Glucose-Induced Diabetic Tilapia: Implications for Therapeutic Intervention

This study investigated the effects of 1- deoxynojirimycin (DNJ) on blood glucose levels, body weight changes, glycogen levels, and carbohydrate marker enzyme activity in a high glucose-induced experimental diabetic tilapia model. We utilized spectrophotometry assay methods to achieve this objective. DNJ treatment significantly reduced blood glucose and mitigated body weight loss compared to the diabetic control group. Furthermore, DNJ treatment increased glycogen levels in liver and muscle tissues, suggesting its potential to enhance glycogen synthesis or reduce glycogen breakdown. DNJ treatment also modulated the activity of carbohydrate marker enzymes, indicating its possible inhibitory effect on enzymes involved in carbohydrate absorption and breakdown, which in turn may improve glucose homeostasis and control. The results of this study highlight DNJ's potential as a therapeutic agent for diseases associated with glycogen metabolism and glucose homeostasis, as well as its ability to influence body weight changes in diabetic conditions. Our findings contribute to the growing body of research on DNJ as a potential therapeutic agent for illnesses linked to glycogen and underscore its therapeutic potential for future treatments targeting glucose metabolism, glycemic control, and weight management.

Dapagliflozin Mitigated Elevated Disomic and Diploid Sperm in a Mouse Model of Diabetes and Recover the Disrupted Ogg1, Parp1, and P53 Gene Expression.

Increases in numerical chromosomal syndromes were observed in children of diabetic mothers. However, the effects of diabetes on male reproduction, specifically numerical chromosomal aberrations (aneuploidy), have not been studied. Furthermore, despite the increasing use of dapagliflozin for diabetes treatment, no data exists on its ability to affect aneuploidy levels in germ cells. Thus, our investigation aimed to evaluate the effects of diabetes on spontaneous sperm aneuploidy and whether treatment with dapagliflozin influences the frequency of aneuploidy in the sperm of an experimental diabetic animal model. Our findings show that dapagliflozin has no aneugenic effects on the meiotic stages of spermatogenesis. In contrast, diabetes raised the frequency of aneuploidy, and dapagliflozin administration decreased the elevated levels of disomic and diploid sperm. The level of oxidative stress was markedly increased in diabetic mice, but were reduced by dapagliflozin treatment. Furthermore, the expression of some of DNA repair genes was disrupted in diabetic animals, whereas dapagliflozin therapy restored these disruptions and significantly enhanced DNA repair. Thus, dapagliflozin may effectively ameliorate diabetes-induced aneugenic effects on male meiosis and treating diabetic patients with dapagliflozin may effectively mitigate the transmission of diabetes-induced chromosomal defects to offspring.

Experimental diabetic animal models to study diabetes and diabetic complications

Diabetes is an endocrine illness involving numerous physiological systems. To understand the intricated pathophysiology and disease progression in diabetes, small animals are still the most relevant model systems, despite the availability and progression in numerous invitro and insilico research methods in recent years. In general, experimental diabetes is instigated mainly due to the effectiveness of animal models in illuminating disease etiology. Most diabetes trials are conducted on rodents, while some research is conducted on larger animals. This review will discuss the methodology and mechanisms in detail for preparing diabetic animal models, considering the following important points. The exact pathophysiology of the disease may or may not be replicated in animal models, the correct induction doses must be given and the combination of different approaches for the models is recommended to get desired results.•Animal models are essential to understand diabetes etiology and pathophysiology.•Diabetic models can be developed in both rodents and non-rodents.•Chemically induced and genetic models of diabetes are widely used to study diabetes and diabetic complications.

Evaluation of the effects of ghrelin and metformin on sperm parameters, testosterone hormones, and immunohistochemical and immunofluorescent markers in an experimental diabetes model

Evaluation of the effects of ghrelin and metformin on sperm parameters, testosterone hormones, and immunohistochemical and immunofluorescent markers in an experimental diabetes model

Clinical and laboratory assessment of hormonal and metabolic disorders in experimental animals with alloxan, streptozotocin and dithizone diabetes

The basic place in experimental diabetology is engaged by chemical models of diabetes. In these patterns, β-cells in pancreatic islet tissue are selectively targeted by diverse agents. Pathogenetic mechanisms of hormonal and metabolic disorders in animals were studied on models of alloxan, streptozotocin and dithizone diabetes. The experiment was carried out on male Wistar rats. Three models of experimental diabetes were created. The groups were equal in terms of observation time (6, 12, 24 months) and number. A complex of laboratory-biochemical methods of lipid and protein metabolism was consumed. Serum enzymes were also determined. The level of glycemia in the studied animals after the introduction of alloxan and streptozotocin ranged from 13.4 to 18.6 mmol/l, glucosuria, polydipsia, polyphagia were observed. A significant (p&lt;0.01) increase in glycemia by 3.10 times, glycated hemoglobin - by 3.16 times, a decrease (p&lt;0.01) of IRI - by 3.76 times and C-peptide - by 2.05 times in animals with streptozotocin diabetes compared with intact animals. Serious lipid metabolism disorders were discovered in alloxan, streptozotocin, and especially dithizone diabetes (24 months of follow-up). This was manifested in a significant (p&lt;0.01) increase in the level of triglycerides - by 1.66 times, atherogenic index (p&lt;0.01) - by 4.43 times and a decrease (p&lt;0.05) in the level of HDL - by 1 43 times compared with the intact CI3 group, as well as an increase in FFA, TCH, LDL, VLDL. In animals with alloxan and dithizone diabetes, the functional activity of the pituitary gland was lessened (the level of growth hormone and CTH (p&lt;0.01), the adrenal cortex and pancreatic α-cells (p&lt;0.01), the activity of the sympathoadrenal system was enlarged, which was reaffirmed by a significant (p&lt;0.01) by an increase in the level of adrenaline, noradrenaline - by 1.42 times. An above pronounced suppression of the endocrine glands was observed in animals with streptozotocin diabetes.