Dose Of Streptozotocin Research Articles

The effect of long-term magnesium treatment on changes in hepatic autophagic and apoptotic ability of type 2 diabetic female rats and their offspring

AimWe investigated the role of magnesium sulfate (MgSO4) and insulin administration on improved autophagy and apoptosis to prevent diabetes in high-fat diet (HFD)-diabetic parents and their offspring. MethodsA HFD and a low dose of streptozotocin (STZ) were used to induce diabetes. Animals were assigned to four groups: non-diabetic control (NDC), diabetic control (DC), the diabetic group received insulin (INS), and the diabetic group received magnesium (MG). The duration of the research was 6 months, and offspring were fed a normal diet for 4 months. Blood glucose was determined weekly in rats (parents and offspring). The gene expression of adenosine monophosphate-activated protein kinase (AMPKα1), Bcl-2-interacting myosin-like coiled-coil protein (Becline-1), P62, Microtubule-associated protein 1 light chain 3 (LC3-II), and caspase-9 of liver tissues were assessed using Real-time PCR. ResultThe analysis of maternal gene expression data showed that treatment with MG and INS considerably augmented the AMPKα1 and LC3-II genes expression and diminished P62 and caspase-9 expression. Also, a significant decrease in the expression of AMPKα1, LC3-II, P62, and Becline-1 was observed in the female offspring in the MG and INS groups. Significant alterations in levels of AMPKα1, Beclin-1, P62, and caspase-9 mRNA were not observed between groups in male offspring, but the expression of LC3-II considerably diminished in the groups compared with the DC group. DiscussionOur data demonstrated that MG supplementation strengthened the mother's autophagy and reduced the transmission of damage to the female offspring. In the male offspring, the transmission of damage was generally less, and MG improved the autophagy condition in the male offspring. Our findings support the presence of a link between autophagy induction and MG-modified biomaterials and determine a potential mechanism of MG-mediated diabetes and autophagy.

Antidiabetic Effect of Passiflora ligularis Leaves in High Fat-Diet/Streptozotocin-Induced Diabetic Mice.

Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of Passiflora ligularis (P. ligularis). For this purpose, T2DM was first induced in mice using a high-fat diet and low doses of streptozotocin. Subsequently, an aqueous extract or an ethanolic extract of P. ligularis leaves was administered for 21 days. The following relevant results were found: fasting blood glucose levels were reduced by up to 41%, and by 29% after an oral glucose overload. The homeostasis model assessment of insulin resistance (HOMA-IR) was reduced by 59%. Histopathologically, better preservation of pancreatic tissue was observed. Regarding oxidative stress parameters, there was an increase of up to 48% in superoxide dismutase (SOD), an increase in catalase (CAT) activity by 35% to 80%, and a decrease in lipid peroxidation (MDA) by 35% to 80% in the liver, kidney, or pancreas. Lastly, regarding the lipid profile, triglycerides (TG) were reduced by up to 30%, total cholesterol (TC) by 35%, and low-density lipoproteins (LDL) by up to 32%, while treatments increased high-density lipoproteins (HDL) by up to 35%. With all the above, we can conclude that P. ligularis leaves showed antihyperglycemic, hypolipidemic, and antioxidant effects, making this species promising for the treatment of T2DM.

The effect of cacao bean extracts on the prevention of periodontal tissue breakdown in diabetic rats with orthodontic tooth movements

ObjectiveProper management of orthodontic treatment in diabetic patients is essential due to the heightened risk of periodontal tissue breakdown associated with hyperglycemia. Cacao bean extracts (CBE) are known to reduce the inflammatory response and increase synthesis and angiogenesis in periodontitis. Therefore, this study aims to examine the effect of CBE on preventing periodontal tissue breakdown in diabetes with orthodontic force. MethodsA total of 25 Wistar rats were divided randomly into 5 groups, including non-diabetes, diabetes, diabetes cacao 125, 250, and 500 mg/kg BW. Diabetic rats were induced with the stratified dose of Streptozotocin, and a 30-g-force from orthodontic device was applied in all groups. Diabetes cacao group was given CBE for 7 days using a gastric probe. GCF samples were used to analyze the eNOS level through the ELISA method. NFκB, Collagen-1, and FGF-2 expression were then assessed using the immunohistochemical method, while the number of fibroblasts and blood vessels was observed using hematoxylin-eosin stained tissue. The data obtained were analyzed with one-way ANOVA and post hoc tests, with p < 0.05. ResultsCBE at a dose of 250 mg/kg BW significantly increased eNOS level, Collagen-1, and FGF-2 expression, and the number of fibroblasts and blood vessels in diabetes groups. Meanwhile, the treatment decreased NFκB expression in diabetes groups (p < 0.05). ConclusionThis study proved that CBE increased periodontal ligament synthesis and angiogenesis and decreased inflammatory response, thereby preventing periodontal tissue breakdown in diabetic rat models with tooth movement.

Changes in the hippocampal level of tau but not beta-amyloid may mediate anxiety-like behavior improvement ensuing from exercise in diabetic female rats

BackgroundIn the present study, we investigated the effect of high-intensity interval training (HIIT) on cognitive behaviors in female rats with a high-fat diet + streptozotocin (STZ)-induced type 2 diabetes.MethodsTwenty-four female rats were divided into four groups randomly (n = 6): control (C), control + exercise (Co + EX), diabetes mellitus (type 2) (T2D), and diabetes mellitus + exercise (T2D + EX). Diabetes was induced by a two-month high-fat diet and a single dose of STZ (35 mg/kg) in the T2D and T2D + EX groups. The Co + EX and T2D + EX groups performed HIIT for eight weeks (five sessions per week, running on a treadmill at 80–100% of VMax, 4–10 intervals). Elevated plus maze (EPM) and open field test (OFT) were used for assessing anxiety-like behaviors, and passive avoidance test (PAT) and Morris water maze (MWM) were applied for evaluating learning and memory. The hippocampal levels of beta-amyloid (Aβ) and Tau were also assessed using Western blot.ResultsAn increase in fasting blood glucose (FBG), hippocampal level of Tau, and a decrease in the percentage of open arm time (%OAT) as an index of anxiety-like behavior were seen in the female diabetic rats which could be reversed by HIIT. In addition, T2D led to a significant decrease in rearing and grooming in the OFT. No significant difference among groups was seen for the latency time in the PAT and learning and memory in the MWM.ConclusionsHIIT could improve anxiety-like behavior at least in part through changes in hippocampal levels of Tau.

Effects of ethanolic extract of &lt;i&gt;Aristolochia repens&lt;/i&gt; on biochemical and histological changes in high-fat diet and streptozotocin-induced rats

The study evaluated the lipid profile, electrolytes and histological changes in diabetic Wistar rats treated with stem bark extract of Aristolochia repens. Type 2 diabetes was induced in rats with high-fat diet and low dose of streptozotocin (35 mg/kg body weight). A total of thirty-five Wistar rats were fed with high-fat diet for eight (8) weeks, while five (5) Wistar rats (Sham control) were fed with low-fat diet. Non-induced male Wistar rats were treated with distilled water (Sham control); while the induced male Wistar rats were treated with distilled water, metformin (100 mg/kg), 50, 100 and 200 mg/kg ethanolic extract of Aristolonchia repens stem bark for 28 days. The rats were sacrificed; liver, kidney and serum were collected and analyzed for serum glucose, lipid profile, electrolytes and histological changes. Treatment with ethanolic extract of Aristolonchia repens stem bark significantly reduced the body weight, glucose level, total cholesterol concentration, triglycerides, low-density lipoprotein concentration and atherogenic indices. Mild pathological alterations were observed in the liver and kidney of diabetic rats at dosage above 50 mg/kg. However, the extract reduced the blood glucose, lipids and improve the selected electrolyte balance. This study suggests that ethanolic extract of stem bark of A. repens possesses antihyperglycaemia and antilipidaemic potential and might not be safe at dosage above 50 mg/kg.

Berberine alleviates diabetic retinopathy by regulating the Th17/Treg ratio

BackgroundDiabetic retinopathy (DR) stands as a prominent complication of diabetes. Berberine (BBR) has reported to be effective to ameliorate the retinal damage of DR. Studying the potential immunological mechanisms of BBR on the streptozotocin (STZ) induced DR mouse model will explain the therapeutic mechanisms of BBR and provide theoretical basis for the clinical application of this drug. MethodsC57BL/6 J mice were induced into a diabetic state using a 50 mg/(kg·d) dose of STZ over a 5-day period. Subsequently, they were subjected to a high-fat diet (HFD) for one month. Following a 5-week treatment with 100 mg/(kg·d) BBR, the concentrations of inflammatory factors in the mice's peripheral blood were determined using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin staining was employed to scrutinize pathological changes in the mice's retinas, while flow cytometry assessed the proportions of T-lymphocyte subsets and the activation status of dendritic cells (DCs) in the spleen and lymph nodes. CD4+T cells and DC2.4 cell lines were utilized to investigate the direct and indirect effects of BBR on T cells under high glucose conditions in vitro. ResultsFollowing 5 weeks of BBR treatment in the streptozotocin (STZ) mouse model of DR, we observed alleviation of retinal lesions and a down-regulation in the secretion of inflammatory cytokines, namely TNF-α, IL-1β, and IL-6, in the serum of these mice. And in the spleen and lymph nodes of these mice, BBR inhibited the proportion of Th17 cells and promoted the proportion of Treg cells, thereby down-regulating the Th17/Treg ratio. Additionally, in vitro experiments, BBR directly inhibited the expression of the transcription factor RORγt and promoted the expression of the transcription factor Foxp3 in T cells, resulting in a down-regulation of the Th17/Treg ratio. Furthermore, BBR indirectly modulated the Th17/Treg ratio by suppressing the secretion of TNF-α, IL-1β, and IL-6 by DCs and enhancing the secretion of indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta (TGF-β) by DCs. This dual action inhibited Th17 cell differentiation while promoting Treg cells. ConclusionOur findings indicate that BBR regulate T cell subpopulation differentiation, reducing the Th17/Treg ratio by directly or indirectly pathway. This represents a potential therapeutic avenue of BBR for improving diabetic retinopathy.

Veratrilla baillonii Franch alleviate the symptoms of diabetes in type 2 diabetic rats induced by high-fat diet and streptozotocin

Our previous research studies have shown that Veratrilla baillonii Franch, a food supplement used by ethnic minorities in Southwest China, has multiple pharmacological activities, such as detoxification, anti-inflammatory, antioxidant, and anti-insulin resistance. However, the detailed signal pathways for its salutary effect on damages in multiple organs due to type 2 diabetes mellitus (T2DM) remains unclear. The current study is to evaluate the therapeutic effects of V. baillonii on T2DM rats and to explore the underlying mechanisms. The T2DM rat model was successfully established by a high-sugar and high-fat diet (HFD) combination with intraperitoneal injection of a small dose of streptozotocin (STZ, 35 mg/kg). Biochemical analysis and histopatholgical examinations were conducted to evaluate the anti-diabetic potential of water extracts of V. baillonii (WVBF). The results showed that the WVBF treatment can improve hyperglycemia and insulin resistance, ameliorate the liver, kidney and pancreas injuries via decreasing inflammatory cytokines such as IL-6 and TNF-α, and oxidative damages. Further investigation suggested that WVBF modulates the signal transductions of the IRS1/PI3K/AKT/GLUT4 and AMPK pathways. These findings demonstrate potentials of WVBF in the treatment of T2DM and possible mechanisms for its hepatoprotective activities.

Vitamin D(3) auto-/paracrine system in rat brain relating to vitamin D(3) status in experimental type 2 diabetes mellitus

Growing evidence suggests that vitamin D3 (D3, cholecalciferol) deficiency and impaired signaling of the hormonally active form of D3, 1α,25(OH)2D3 (1,25D3), through its cellular receptor (VDR) can be significant risk factors for the development of numerous multifactorial diseases, including diabetes. Our investigation was aimed at researching the D3 status in relation to the state of the D3 auto-/paracrine system in the brain and clarifying the effectiveness of the therapeutic use of D3 as a neuroprotective agent in experimental type 2 diabetes mellitus (T2DM). T2DM was induced in male Wistar rats by a combination of a high fat diet and a low dose of streptozotocin (25 mg/kg BW). Diabetic animals were treated with or without cholecalciferol (1,000 IU/kg BW, 30 days). The content of 25-hydroxyvitamin D3 (25D3) in blood serum and brain tissue was determined by ELISA. Analysis of mRNA expression of CYP24A1 and CYP27B1 genes was performed by RT-PCR. Protein levels of VDR, vitamin D3 binding protein (VDBP), CYP27B1 and CYP24A1 were investigated by Western blotting. A significant T2DM-associated decrease in the content of 25D3 in the blood serum was revealed, which correlated with a reduced content of this metabolite in the brain tissue. Impaired D3 status in animals with T2DM was accompanied by an increase in the levels of mRNA and protein of both 25D3 lα-hydroxylase (CYP27B1) and 1,25-hydroxyvitamin D3-24-hydroxylase (CYP24A1), which, respectively, provide local formation and degradation in the nervous tissue of the hormonally active form of D3 – 1,25D3. At the same time, a significant T2DM-induced down-regulation of the brain content of VDBP was shown. In addition, diabetes caused a slight increase in the protein expression of the VDR, through which the auto-/paracrine effects of 1,25D3 are realized in the brain. We have established a complete or partial corrective effect of cholecalciferol on D3 status, its bioavailability in the CNS and the level of protein expression of CYP27B1 and CYP24A1 in the brain of rats with T2DM. Abnormal D3 status in animals with T2DM was accompanied by compensatory changes in the expression of key components of the auto-/paracrine vitamin D3 system. Cholecalciferol was demonstrated to be partially effective in counteracting the impairments caused by T2DM. Keywords: 25-hydroxyvitamin D3, brain, type 2 diabetes, vitamin D3, vitamin D3 auto-/paracrine system

Вплив блокади клітинних протеїнкіназ на обмін речовин при експериментальному цукровому діабеті

Prospective use of receptor protein kinase inhibitors (PKI) for the prevention and/or treatment of diabetic complications necessitates the study of their effect on carbohydrate, lipid, and protein metabolism in experimental models of type 1 (DM1) and type 2 (DM2) diabetes. DM1 was modeled in male Wistar rats with streptozotocin administration (50 mg/ kg), DM2 – by long-term (180 days) maintenance on a highcalorie fat diet (HFD; 56,7% fat) with the introduction of a lower dose of streptozotocin (25 mg/kg). For the treatment, we used insulin (“Actrapid Novo Nordisk”, Denmark) and a PKI inhibitor Sorafenib (“Cipla”, India), added orally in sachet form (150 mg/kg). Regardless of the diet type, the streptozotocin administration led to hyperglycemia, weight loss, glucose- and ketonuria, polyuria, and polydipsia. The severity of these manifestations was heightened in HFD rats, with a mortality rate of 53.3% observed (when modeling DM1 – 12%), likely attributed to the onset of liver failure. In HFD rats, slight hyperglycemia was noted only on the 150th day. All the diabetes models used were accompanied by significant hypercholesterolemia and hyperlipidemia. The addition of glucose to HFD rats increased the cholesterol content. HFD caused hypoproteinemia, metabolism suppression and increased transaminases activity. The established violations were largely restored with the use of PKI: glycemia level, body weight loss, the content of triglycerides and very low-density lipoproteins decreased; an increase in high-density lipoproteins and the normalization of pigment metabolism were observed.

Rosmarinus officinalis extract ameliorates cognitive deficits and hippocampal neurogenesis in mice model of diabetes mellitus

RationaleDiabetes mellitus causes cognitive impairment and negatively affects the hippocampal integrity and neurogenesis. The impaired insulin activity and secretion contribute to the down-regulation of fibroblast growth factor which is an important stimulant of the neurogenic process. The present study elucidated the potential effects of Rosmarinus officinalis, (R. officinalis) on spatial memory and adult hippocampal neurogenesis in diabetic mice model using behavioral tests, histological and immunohistochemical analysis. Material and methodsThe male Balb/c mice were administered a high-fat diet and streptozotocin (STZ) (100 mg/kg i.p.) at 6th and 9th week of age. Following that, 36 h after second dose of STZ, 50 mg/kg R. officinalis extract was administered orally for 21 days. ResultsSTZ and a high-fat diet caused diabetes that led to the defects in learning and memory and compromised the process of hippocampal neurogenesis. Interestingly, R. officinalis improved cognitive functions and increased the expression of neurogenic markers including KI67 and NeuN, suggesting an improvement in the process of adult hippocampal neurogenesis. ConclusionsIt has been suggested that R. officinalis may act as a potential agent for the improvement of neurodegeneration and learning and memory deficits associated with diabetes. These findings warrant further investigation of the specific active constituents of R. officinalis involved in the regulation of these molecular processes to be considered as novel adjunctive therapy for diabetes mellitus-associated neurological consequences.

Cyclophilin D knockout significantly prevents HCC development in a streptozotocin-induced mouse model of diabetes-linked NASH.

A family of Peptidyl-prolyl isomerases (PPIases), called Cyclophilins, localize to numerous intracellular and extracellular locations where they contribute to a variety of essential functions. We previously reported that non-immunosuppressive pan-cyclophilin inhibitor drugs like reconfilstat (CRV431) or NV556 decreased multiple aspects of non-alcoholic fatty liver disease (NAFLD) in mice under two different non-alcoholic steatohepatitis (NASH) mouse models. Both CRV431 and NV556 inhibit several cyclophilin isoforms, among which cyclophilin D (CypD) has not been previously investigated in this context. It is unknown whether it is necessary to simultaneously inhibit multiple cyclophilin family members to achieve therapeutic benefits or if loss-of-function of one is sufficient. Furthermore, narrowing down the isoform most responsible for a particular aspect of NAFLD/NASH, such as hepatocellular carcinoma (HCC), would allow for more precise future therapies. Features of human diabetes-linked NAFLD/NASH can be reliably replicated in mice by administering a single high dose of streptozotocin to disrupt pancreatic beta cells, in conjunction with a high sugar, high fat, high cholesterol western diet over the course of 30 weeks. Here we show that while both wild-type (WT) and Ppif-/- CypD KO mice develop multipe severe NASH disease features under this model, the formation of HCC nodules was significantly blunted only in the CypD KO mice. Furthermore, of differentially expressed transcripts in a qPCR panel of select HCC-related genes, nearly all were downregulated in the CypD KO background. Cyclophilin inhibition is a promising and novel avenue of treatment for diet-induced NAFLD/NASH. This study highlights the impact of CypD loss-of-function on the development of HCC, one of the most severe disease outcomes.

Aberrant splicing of CaV1.2 calcium channel induced by decreased Rbfox1 enhances arterial constriction during diabetic hyperglycemia

Diabetic hyperglycemia induces dysfunctions of arterial smooth muscle, leading to diabetic vascular complications. The CaV1.2 calcium channel is one primary pathway for Ca2+ influx, which initiates vasoconstriction. However, the long-term regulation mechanism(s) for vascular CaV1.2 functions under hyperglycemic condition remains unknown. Here, Sprague–Dawley rats fed with high-fat diet in combination with low dose streptozotocin and Goto-Kakizaki (GK) rats were used as diabetic models. Isolated mesenteric arteries (MAs) and vascular smooth muscle cells (VSMCs) from rat models were used to assess K+-induced arterial constriction and CaV1.2 channel functions using vascular myograph and whole-cell patch clamp, respectively. K+-induced vasoconstriction is persistently enhanced in the MAs from diabetic rats, and CaV1.2 alternative spliced exon 9* is increased, while exon 33 is decreased in rat diabetic arteries. Furthermore, CaV1.2 channels exhibit hyperpolarized current–voltage and activation curve in VSMCs from diabetic rats, which facilitates the channel function. Unexpectedly, the application of glycated serum (GS), mimicking advanced glycation end-products (AGEs), but not glucose, downregulates the expression of the splicing factor Rbfox1 in VSMCs. Moreover, GS application or Rbfox1 knockdown dynamically regulates alternative exons 9* and 33, leading to facilitated functions of CaV1.2 channels in VSMCs and MAs. Notably, GS increases K+-induced intracellular calcium concentration of VSMCs and the vasoconstriction of MAs. These results reveal that AGEs, not glucose, long-termly regulates CaV1.2 alternative splicing events by decreasing Rbfox1 expression, thereby enhancing channel functions and increasing vasoconstriction under diabetic hyperglycemia. This study identifies the specific molecular mechanism for enhanced vasoconstriction under hyperglycemia, providing a potential target for managing diabetic vascular complications.

Chemical characterization and effect of Ziziphora clinopodioides green-synthesized silver nanoparticles on cytotoxicity, antioxidant, and antidiabetic activities in streptozotocin-induced hepatotoxicity in Wistar diabetic male rats.

The present research studied the cytotoxicity, antioxidant, and antidiabetic activities of biogenically synthesized silver nanoparticles (AgNPs) using Ziziphora clinopodioides (Z. clinopodioides) as a green mediator. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy (UV-Vis) were employed to determine AgNPs. In the invivo experiment, the model rats were categorized into different groups receiving 50, 100, 200, and 400 μg/kg of AgNPs and diabetic, positive, and normal groups (n = 10) using a random division. A single dose of streptozotocin (STZ) at 60 mg/kg was administered to induce diabetes and hepatotoxicity in rats. The administration of AgNPs was performed via intragastric administration for 25 days. On the final day, the levels of glucose and biochemical enzymes, namely aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT), and gamma-glutamyltransferase (GGT), were assessed in the serum. Following tissue processing, liver sections with a thickness of 5 μm were prepared. Later, the total volume of different liver components, such as hepatocytes, sinusoids, portal vein, central vein, hepatic arteries, and bile ducts, was measured. The portal vein and bile duct volumes did not vary significantly in groups treated by AgNPs. However, the volume of the central vein and hepatic arteries exhibited noticeable variations in groups treated by AgNPs. After administration of streptozotocin, the volume of hepatocytes and sinusoids increased significantly. However, treatment with a high dose of AgNPs significantly decreased the volume of hepatocytes and sinusoids. In diabetic rats, administering AgNPs reduced the fasting blood glucose levels compared to the model group. In addition, AgNPs decreased the elevated levels of AST and ALP enzymes in a manner that depended on the dosage of AgNPs used. This research demonstrates the hepatoprotective and antidiabetic properties of AgNPs, suggesting their potential implications as hepatoprotective and antidiabetic supplements to prevent diabetes.

Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model.

The American Diabetes Association guidelines (2021) confirmed the importance of raising public awareness of diabetes-induced cognitive impairment, highlighting the links between poor glycemic control and cognitive impairment. The characteristic brain lesions of cognitive dysfunction are neurofibrillary tangles (NFT) and senile plaques formed of amyloid-β deposition, glycogen synthase kinase 3 beta (GSK3β), and highly homologous kinase tau tubulin kinase 1 (TTBK1) can phosphorylate Tau proteins at different sites, overexpression of these enzymes produces extensive phosphorylation of Tau proteins making them insoluble and enhance NFT formation, which impairs cognitive functions. The current study aimed to investigate the potential contribution of liraglutide and pramlintide in the prevention of diabetes-induced cognitive dysfunction and their effect on the PI3K/AKT/GSK-3β/TTBK1 pathway in type 2 diabetic (T2D) rat model. T2D was induced by administration of a high-fat diet for 10weeks, then injection of a single dose of streptozotocin (STZ); treatment was started with either pramlintide (200μg/kg/day sc) or liraglutide (0.6mg/kg/day sc) for 6weeks in addition to the HFD. At the end of the study, cognitive functions were assessed by novel object recognition and T-maze tests. Then, rats were sacrificed for biochemical and histological assessment of the hippocampal tissue. Both pramlintide and liraglutide treatment revealed equally adequate control of diabetes, prevented the decline in memory function, and increased PI3K/AKT expression while decreasing GSK-3β/TTBK1 expression; however, liraglutide significantly decreased the number of Tau positive cells better than pramlintide did. This study confirmed that pramlintide and liraglutide are promising antidiabetic medications that could prevent associated cognitive disorders in different mechanisms.

Integrative analysis on the effects of streptozotocin in the experimental model for diabetization in wistar rats: histological and laboratory study

The study of complications of diabetes mellitus is important to understand the alterations on the specific tissues affected by this chronic disease. An animal model that simulated this complication is necessary for further treatments and prevention of diabetes complications. The aim of this study was evaluated the biochemical and histological alterations on liver, kidney, small gut and retina tissues. The animal assay was made with 15 wistar rats divided in two groups: a control group, consisting of 5 rats that were healthy and non-diabetic (CONTROL), and a streptozotocin group (STZ), consisting of 10 rats who were diabetic. A dosage of streptozotocin at a concentration of 40 mg/kg was administered intraperitoneally. Rats with glycemia levels below 150 mg/dl received a subsequent injection of 40 mg/kg of streptozotocin, whereas rats with glycemia levels ranging from 150 to 250 mg/dl were given a subsequent injection of 20 mg/kg of streptozotocin. The biochemical results showed difference in triglyceride, AST and ALT levels between the groups. The histological analysis of liver, kidney, small gut and retina showed significant alterations related to the chronic diabetes complications. These results suggested that this animal model can be used for future studies of metabolics mechanisms to undertand and avoid the complications of diabetes.

Investigating the mechanism of cornel iridoid glycosides on type 2 diabetes mellitus using serum and urine metabolites in rats

Ethnopharmacological relevanceCornel iridoid glycosides (CIG) are extracted from Corni fructus, a herbal medicine used in traditional Chinese medicine to treat diabetes. However, the antidiabetic effects of CIG and the underlying metabolic mechanisms require further exploration. Aim of the studyThis study aimed to assess the antidiabetic effects and metabolic mechanism of CIG by performing metabolomic analyses of serum and urine samples of rats. Materials and methodsA rat model of type 2 diabetes mellitus (T2DM) was established by administering a low dose of streptozotocin (30 mg/kg) intraperitoneally after 4 weeks of feeding a high-fat diet. The model was evaluated based on several parameters, including fasting blood glucose (FBG), random blood glucose (RBG), urine volume, liver index, body weight, histopathological sections, and serum biochemical parameters. Subsequently, serum and urine metabolomics were analyzed using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS). Data were analyzed using unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares discriminant analysis (OPLS-DA). Differential metabolites were examined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways to explore the underlying mechanisms. ResultsAfter 4 weeks of treatment with different doses of CIG, varying degrees of antidiabetic effects were observed, along with reduced liver and pancreatic injury, and improved oxidative stress levels. Compared with the T2DM group, 19 and 23 differential metabolites were detected in the serum and urine of the CIG treatment group, respectively. The key metabolites involved in pathway regulation include taurine, chenodeoxycholic acid, glycocholic acid, and L-tyrosine in the serum and glycine, hippuric acid, phenylacetylglycine, citric acid, and D-glucuronic acid in the urine, which are related to lipid, amino acid, energy, and carbohydrate metabolism. ConclusionsThis study confirmed the antidiabetic effects of CIG and revealed that CIG effectively controlled metabolic disorders in T2DM rats. This seems to be meaningful for the clinical application of CIG, and can benefit further studies on CIG mechanism.

The effect of Artemisia annua L. aqueous and methanolic extracts on insulin signaling in liver of HFD/STZ diabetic mice.

Many studies have shown the anti-diabetic effects of medicinal plants. But their molecular mechanism has been less studied. Understanding of these mechanisms can help to better manage the treatment of diabetes by using these plants. So, this research examined the effect of Artemisia annua extract on PI3K (phosphatidylinositol 3-kinase)/AKt (serine/threonine kinase protein B) signaling pathway in liver of high-fat diet (HFD)/Streptozotocin (STZ)-induced type 2 diabetic mice. Groups of mice were control, untreated diabetic mice, diabetic mice treated with various doses (400, 200, 100 mg/kg) of methanolic and aqueous extract of A. annua and metformin for four weeks. Type 2 diabetes was produced by feeding high-fat diet following injection of low dose of STZ. After experiment duration all mice were sacrificed and blood glucose, insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), index of insulin sensitivity index (ISI) were detected and liver tissues were isolated for to detect m-RNA expression of PI3K and Akt. Extracts of aqueous and methanolic this plant markedly reduced hyperglycemia, hyperinsulinemia, HOMA-IR and elevated ISI in diabetic group in comparison with un-treated diabetic mice. In addition, they could enhance the expression of AKt and PI3K m-RNA in liver tissues in diabetic mice. Artemisia annua extract ameliorated insulin resistance and improved insulin action in liver via the high activity of PI3K/AKt signaling pathway. So, it can be a suitable alternative treatment to synthetic antidiabetic drugs to improve insulin action in condition of type 2 diabetes.

Yunvjian decoction mitigates hyperglycemia in rats induced by a high-fat diet and streptozotocin via reducing oxidative stress in pancreatic beta cells

Ethnopharmacological relevanceYunvjian (YNJ), a traditional Chinese herbal formula first reported in Jing Yue Quan Shu, is commonly used in the clinical treatment of type 2 diabetes mellitus (T2DM). However, the mechanism by which YNJ affects T2DM remains unclear. Aim of the studyThis study aimed to assess the therapeutic effects of YNJ on T2DM and explore the potential mechanism involved. Materials and methodsHigh-performance liquid chromatography (HPLC) was used to identify the chemical compounds of YNJ. The anti-T2DM effects of YNJ were observed in a high-fat diet/streptozotocin induced rat model. The type 2 diabetic rats were prepared as follows: rats were fed a high-fat diet for four weeks and then intraperitoneally injected with a low dose (30 mg/kg) of streptozotocin. YNJ and the positive control metformin were used in these experiments. Biochemical assays were implemented to determine the fasting blood glucose, glucose tolerance, insulin sensitivity, serum lipid levels, and oxidative stress index of the pancreas. Hematoxylin-eosin (H&E) staining was used to assess histopathological alterations in the pancreas. The mechanism by which YNJ affects T2DM was evaluated in INS-1 cells treated with glucose and high sodium palmitate. YNJ-supplemented serum was used in these experiments. Methyl thiazolyl tetrazolium assays, enzyme-linked immunosorbent assays, Nile red staining, flow cytometric analysis, and Western blotting were used to assess apoptosis, insulin secretion, lipid accumulation, reactive oxygen species production, and protein levels. ResultsFive major compounds were identified in YNJ. In high-fat diet/streptozotocin-induced diabetic rats, YNJ-M notably decreased fasting blood glucose and lipid levels; ameliorated glucose tolerance, insulin sensitivity, and islet morphology; reduced Malondialdehyde levels; and restored superoxide dismutase activity in the pancreatic islets. Furthermore, the effect of YNJ-M was significantly greater than that of YNJ-L, and YNJ-H had little effect on diabetic rats. In vitro experiments revealed that YNJ-supplemented serum (10%, 15%, and 20%) dramatically suppressed apoptosis, mitigated intracellular lipid accumulation and reduced intracellular oxidative stress levels in a dose-dependent manner. Additionally, YNJ-supplemented serum increased the protein expression of Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, and superoxide dismutase 1 and inhibited the protein expression of Kelch-like ECH-associated protein 1. ConclusionYNJ ameliorates high-fat diet/streptozotocin induced experimental T2DM. The underlying mechanism involves reducing oxidative stress in pancreatic beta cells. The findings of this study provide scientific justification for the application of the traditional medicine YNJ in treating T2DM.

Antidiabetic Properties of Stingless Bee Pollen in High-Fat Diet FED-Low Dose STZ Induced Experimental T2DM Rats

Diabetes mellitus (DM) is a multisystem metabolic disease because of either insulin insufficiency or ineffectiveness. Individuals with DM continuously measure their blood glucose levels during fasting and after eating in order to manage their condition effectively. glucose levels during fasting and after eating in order to manage their condition effectively. Despite the availability of several drugs, there is no treatment proven to be perfect due to adverse side impacts as well as reduced long-term efficacy. Moreover, the excessive formation of free radicals has been linked to diabetes progression, development, as well as complications. As a result, there is a need to explore new medicines without side effects, preferably derived from natural products. Therefore, this study analyzes the antidiabetic properties of stingless bee pollen scientifically. This natural product was fed a high-fat diet and low streptozotocin doses in experimental rats with T2DM. An oral glucose tolerance test aimed investigate stingless bee pollen effect on glucose homeostasis. An insulin toleration test was executed to obtain stingless pollen influence on insulin sensitivity. This study measures Insulin resistance with HOMA-IR. Oral administration of stingless bee pollen for 30 days raised glucose homeostasis in T2DM rats, as shown by the OGTT, ITT, and HOMA-IR results. In addition, this treatment significantly improved changes in glycated hemoglobin, fasting blood glucose, protein, uric acid, urea, as well as creatinine levels. The activity changes of ALP, AST, and ALT liver enzyme markers in T2DM rats were nearly normalized after given with stingless bee pollen. The activity of carbohydrate metabolism enzymes includes pyruvate kinase, glucokinase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, fructose-1,6-bisphosphatase and lactate dehydrogenase in T2DM rats’ liver tissue. This change was significantly restored to near-normal levels after stingless bee pollen treatment.&#x0D; Keywords: Diabetes Mellitus, High Fat Diet, Metformin, Stingless Bee Pollen

Dapagliflozin Pretreatment Prevents Cardiac Electrophysiological Changes in a Diet and Streptozotocin Induction of Type 2 Diabetes in Rats: A Potential New First-Line?

Dapagliflozin exerts cardioprotective effects in Type 2 Diabetes Mellitus (T2DM). However, whether these effects prevent electrocardiographic changes associated with T2DM altogether remain unknown. Our aim was to investigate the prophylactic effect of dapagliflozin pretreatment on the rat ECG using a high-fat, high-fructose (HFHf) diet and a low dose streptozotocin (STZ) model of T2DM. Twenty-five (25) rats were randomized into five (5) groups: normal control receiving a normal diet while the other groups received an 8-week HFHf and 40mg/kg STZ on day 42, and either: saline for the diabetic control (1 mg/kg/d), low dose (1.0 mg/kg/d) and high dose dapagliflozin (1.6 mg/kg/d), or metformin (250 mg/kg/d). Oral glucose tolerance (OGT), electrocardiograms (ECGs), paracardial adipose mass, and left ventricular fibrosis were determined. Data were analyzed using GraphPad version 9.0.0.121, with the level of significance at p < 0.05. Compared to the diabetic control group, a high dose of dapagliflozin preserved the OGT (p = 0.0001), QRS-duration (p = 0.0263), QT-interval (p = 0.0399), and QTc intervals (p = 0.0463). Furthermore, the high dose dapagliflozin group had the lowest paracardial adipose mass (p = 0.0104) and fibrotic area (p = 0.0001). In contrast, while metformin showed favorable effects on OGT (p = 0.0025), paracardial adiposity (p = 0.0153) and ventricular fibrosis (p = 0.0291), it did not demonstrate significant antiarrhythmic effects. Pretreatment with higher doses of Dapagliflozin exhibits prophylactic cardioprotective characteristics against diabetic cardiomyopathy that include antifibrotic and antiarrhythmic qualities. This suggests that higher doses of dapagliflozin could be a more effective initial therapeutic option in T2DM.