Diabetic Model Group Research Articles

Mechanism of the cardioprotective effect of empagliflozin on diabetic nephropathy mice based on the basis of proteomics

Diabetic nephropathy affects a significant proportion of individuals with diabetes, and its progression often leads to cardiovascular disease and infections before the need for renal replacement therapy arises. Empagliflozin has been shown to have various protective effects in cardiovascular disease studies, such as improving diabetic myocardial structure and function, and reducing myocardial oxidative stress. However, the impact of empagliflozin on cardiac protein expression and signaling pathways has not been comprehensively analyzed. To address this gap, we conducted proteome analysis to identify specific protein markers in cardiac tissue from the diabetes model group, including Myh7, Wdr37, Eif3k, Acot1, Acot2, Cat, and Scp2, in cardiac tissue from the diabetes model group. In our drug model, empagliflozin primarily modulates the fat-related metabolic signaling pathway within the heart. Empagliflozin downregulated the protein expression levels of ACOX1, ACADVL and CPT1A in the model group. Overall, our findings demonstrate that empagliflozin provides cardiac protection by targeting metabolic signaling pathways, particularly those related to fat metabolism. Moreover, the identification of cardiac biomarkers in a mouse model of diabetic nephropathy lays the foundation for further exploration of disease biomarkers in cardiac tissue.

Renal protective effect of Isaria felina mycelium powder on diet and STZ-induced diabetes mice and the identification of major chemical constituents

Type 2 diabetes is a group of metabolic diseases mainly characterized by chronic hyperglycemia. Diabetic kidney disease is the most common microvascular complication of diabetes.The aim of this study was to investigate the therapeutic effect of Isaria felina mycelium powder (IFMP) on diet and streptozotocin (STZ)-induced diabetic mouse model. And we analyze the main chemical constituents of Isaria felina mycelium powder.The main chemical constituents of the alcohol-soluble IFMP were prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). The fasting blood glucose and renal index of the mouse model was determined. Serum levels of triglyceride (TG), total cholesterol (TC), serum creatinine (Scr) and blood urea nitrogen (BUN) were detected. The levels of CD2AP and nephrin proteins in the kidney were detected by ELISA kits.A total of 32 compounds were identified, including nucleosides (16 types), amino acids (13 types), sterols (one type) and glycosides (two types). The experimental results showed that compared with the diabetes model group, IFMP reduced fasting blood glucose, food intake and water intake. Biochemical analysis indicated that IFMP reduced the serum levels of TG, TC, BUN and Scr, and increased the levels of CD2AP and nephrin proteins in the kidneys.Therefore, IFMP has the potential to treat diabetes and prevent kidney damage induced by hyperglycemia.

Quercetin ameliorates diabetic kidney injury in rats by inhibiting the HMGB1/RAGE/NF-κB signaling pathway

To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms. Twenty-four adult male SD rats were randomized equally into normal control group, high-glucose and high-fat feeding group, streptozotocin (STZ) -induced diabetic model group, and quercetin treatment (daily dose 100 mg/kg) group. Pathological changes of the renal tissues of the rats were observed with HE staining, serum inflammatory factor levels were determined with ELISA, and renal expression of NF‑κB was observed by immunohistochemistry. Fast blood glucose (FBG), serum levels of triglyceride (TG), BUN, and Scr, and 24-h urine protein content of the rats were measured, and renal expressions of HMGB1, RAGE, NF‑κB, Bax, Bcl-2, and caspase-3 were detected with Western blotting. The diabetic rats showed significantly increased levels of FBG, TG, BUN, and Scr, renal hypertrophy index, 24-h urinary protein content, serum IL-1β, IL-6 and TNF-α levels and renal expressions HMGB1, RAGE, NF‑κB, Bax, and caspase-3 with decreased renal expression of Bcl-2. All these changes were significantly alleviated by quercetin treatment of the rats. Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Preparation of a hydrolyzed yeast β-glucan chromium(III) complex and evaluation of its hypoglycemic activity and sub-acute toxicity

Yeast β-glucan (BYG) possesses extremely low solubility that has limited its applications. In this study, we hydrolyzed BYG using snail enzyme to obtain hydrolyzed yeast β-glucan (HBYG) with desirable water solubility and hypoglycemic activity. On the basis of HBYG, HBYG‑chromium(III) complex (HBYG-Cr) was synthesized. The molecular weight of the complex was 4.41 × 104 Da, and the content of trivalent chromium was 8.95 %. The hydroxyl groups of HBYG participated in the coordination and formed the chromium complex. The space conformations of HBYG exhibited remarkable changes after complex formation. HBYG-Cr existed mainly in an amorphous state and presented good dispersibility, and the surface was uneven. The hypoglycemic activity of HBYG-Cr was studied in db/db and C57 mice. The results showed that HBYG-Cr had good hypoglycemic activity. Histopathological studies demonstrated that the liver, kidney, pancreas, and skeletal muscle in the treatment group were significantly improved compared with those in the diabetic model group. The sub-acute toxicity of HBYG-Cr was studied in KM mice and the results indicated that the complex did not cause adverse reactions or toxic side effects. This study broadened the application of yeast β-glucan and provided an important reference for the development of hypoglycemic functional foods and drugs.

Anti-inflammatory Effects of Channa micropeltes Extract through NF-κB and TNF-α in Diabetic Rat

Diabetes mellitus (DM) is a disorder of carbohydrate, fat, and protein metabolism caused by impaired insulin secretion, insulin action, or both characterized by hyperglycemia. Hyperglycemic condition is associated with inflammation process leading to complications. Food supplements play an important role in controlling protein metabolism and have anti-inflammatory properties such as Channa micropeltes (CM). This study aimed to analyze the effect of CM extract on the levels of molecular markers Nuclear factor kappa beta (NF-κB) and Tumor Necrosis Factor alfa (TNF-α) in normal and diabetic rats. The experimental design of this investigation was a post-test-only control group design and the samples were the diabetic model group given CM extract at 16 mL/kgBB dose, and negative control group for 14 days, respectively. Serum concentrations of NF-κB and TNF-α were measured by ELISA. DM-CM group showed decreasing levels of NF-κB. TNF- α was detected with the lowest level in the N-CM group. The levels of TNF- α declined close to normal levels in the DM-CM group. Hence, the conclusion was the CM at a dose of 16 mL/kg BW for 14 days in Wistar rats can reduce Nf-κB and TNF-α in groups of normal and diabetic rats.

The Active Ingredient Catalpol in Rehmannia glutinosa Reduces Blood Glucose in Diabetic Rats via the AMPK Pathway.

Type 2 diabetes mellitus (T2DM) poses a huge threat to population health globally, and more drugs need to be explored for treatment. In this study, we investigated the mechanism of active ingredient catalpol in Rehmannia glutinosa on reduces blood glucose in diabetic. The T2DM model was constructed by intraperitoneal injection of streptozotocin into Sprague-Dawley (SD) rats, which were randomly grouped into diabetes model group, pioglitazone group, Rehmannia glutinosa group, catalpol high-dose group, catalpol low-dose group and normal control group.The intervention was continued for 28 d, and changes in body weight, fasting blood glucose, insulin and lipid levels were observed. Of all the drugs, pioglitazone had the most pronounced hypoglycemic effect, which began to decline after 2 weeks of treatment in the low-dose catalpol group and had no hypoglycemic effect in the high-dose catalpol group. Among them, Rehmannia glutinosa was able to increase serum triglyceride level, and pioglitazone effectively reduced total cholesterol level in rats. The low dose of catalpol decreased the concentration of low-density lipoprotein cholesterol (LDL), while the high dose of catalpol increased the concentration of LDL. As an active ingredient in Rehmannia glutinosa, catalpol has the potential to lower blood glucose and improve blood lipids in diabetes treatment, and its action may be achieved by regulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, which provides a new idea for the development of new diabetes therapeutic approaches.

Effect of metformin nanoemulsion through AMP-activated protein kinase (AMPK)-mediated autophagy on diabetic neuropathy

Metformin (MET) is the preferred first-line treatment for patients with type 2 diabetes. However, the mechanism of diabetic peripheral neuropathy (DPN) is still unclear. To improve the oral utilization of metformin, a metformin nanoemulsion (MET-NE) was prepared to investigate its effects on DPN and its underlying mechanism. In this study, a DPN model was established in Wistar rats induced by streptozotocin (STZ). The diabetic rats were randomly divided into four groups: the diabetic model group (DM group), the metformin tablet-treated group (MET group), the metformin nanoemulsion-treated group (MET-NE group), and a normal control group consisting of five normal Wistar rats. All groups were administered the treatment orally for a period of 10 weeks. The findings of the study demonstrated that both MET and MET-NE significantly reduced blood glucose levels, glycated serum protein levels, food intake, and water intake in DM rats. It was also observed that MET-NE was more effective than MET in reducing blood glucose levels. Additionally, both MET and MET-NE treatments significantly increased the motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), and sensory nerve action potential (SNAP) amplitude in DM rats. Furthermore, these treatments improved mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), resulting in a reduced sensitivity to pain stimuli. Moreover, both MET and MET-NE treatments promoted the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) proteins, as well as increased the activity of autophagic proteins in the sciatic nerve. However, no significant differences were observed between MET and MET-NE treatments in terms of these effects. In conclusion, the MET-NE demonstrated a rapid decrease in blood glucose levels and improved glucose tolerance and metabolism, which was found to be superior to MET. Furthermore, MET-NE significantly improved the neurophysiological function and sciatic nerve pain threshold in DPN rats. These beneficial effects may be attributed to the regulation of AMPK-mediated autophagy by MET-NE.

Hippocampal transcriptome analysis reveals mechanisms of cognitive impairment in beagle dogs with type 1 diabetes.

Diabetic encephalopathy is a common complication of type 1 diabetes. However, there have been few studies on cognitive impairment and hippocampal damage in type 1 diabetes mellitus (T1DM) using dogs as experimental animals. To investigate the effects of diabetes on the CNS, 40 adult beagles were divided into streptozotocin/alloxan type 1 diabetes model and control groups. The duration of diabetes in the model group was 120 days. A cognitive dysfunction scale was used to assess cognitive function. Hematoxylin and eosin and Golgi-Cox staining methods were used to observe morphological damage to the hippocampus. Transcriptomics was used to investigate differential gene expression in the hippocampus. The results showed that the cognitive dysfunction score of the model group was significantly higher than that of the control group. In addition, the number of normal neurons, the complexity of dendritic morphology, and the density of dendritic spines were decreased in the hippocampus of diabetic dogs. A total of 672 differentially expressed genes (DEGs) were identified, 289 of which were upregulated, and 383 were downregulated. Modified genes included DBH, IGFBP2, AVPR1A, and DRAXIN. In conclusion, type 1 diabetic dogs exhibit cognitive dysfunction. The DEGs were mainly enriched in metabolic, PI3K-Akt signaling, and neuroactive ligand-receptor interaction pathways.

Astaxanthin could regulate the gut-kidney axis to mitigate kidney injury in high-fat diet/streptozotocin-induced diabetic mice.

Accumulating evidences have shown the beneficial effects of astaxanthin (AST) supplementation on metabolic diseases prevention and treatment. The goal of present study was to reveal the favorable interactions among AST supplementation, gut microbiota, and kidneys in vivo, so as to attenuate kidney impairment in diabetic mice. Twenty C57BL/6J mice were assigned to a normal control group and a diabetic model group induced by a high-fat diet plus low-dose streptozotocin, and then the diabetic mice were fed with a high-fat diet without or with AST [0.01% (AST_a) or 0.02% (AST_b)] for 12 weeks. When compared to the diabetes kidney disease (DKD) group, AST supplementation delayed the renal pathological progression, reduced fasting blood glucose (AST_b: 1.53-fold, p<0.05), repressed levels of lipopolysaccharide (LPS; AST_a: 1.24-fold, p=0.008; AST_b: 1.43-fold, p<0.001) and TMAO (AST_a: 1.51-fold, p=0.001; AST_b: 1.40-fold, p=0.003), inhibited IL-6 (AST_a: 1.40-fold, p=0.004; AST_b: 1.57-fold, p=0.001) and reactive oxygen species (ROS; AST_a: 1.30-fold, p=0.004; AST_b: 1.53-fold, p<0.001), as well as regulated the Sirt1/PGC-1α/NFκB p65 signaling pathway. Moreover, the results of 16S rRNA gene-based Illumina deep sequencing in each group revealed that dietary AST supplementation also favorably modulated the gut microbiota compared with the DKD group, as evidenced by the inhibition of the harmful bacteria Clostridium_sensu_stricto_1, Romboutsia, and Coriobacteriaceae_UCG-002, and the enhancement of the probiotics such as Lachnospiraceae_NK4A136_group, Roseburia, and Ruminococcaceae. Taken together, dietary AST supplementation could protect kidneys against inflammation and oxidative stress by adjusting the gut-kidney axis in diabetic mice.

Antidiabetic Effect of Chinese yam (Dioscorea opposita Thunb.) in High‐Fat Diet/Streptozotocin‐Induced Diabetic Rats

AbstractThis study aims to assess the effect of different doses of Chinese yam (CY) on a high‐fat diet (HFD) and a streptozotocin‐induced diabetic rat model, using resistant starch (RS) as a positive control. Rats in the normal control and diabetes model (DM) groups are fed the standard diet and HFD, respectively. The RS and CY‐intervention groups are fed with a special HFD, in which starch, maltodextrin, and sucrose in the HFD are replaced completely with RS or CY powder in different proportions: 33.33% (1/3), 66.67% (2/3), and 100% respectively. The results show that CY powder can decrease serum levels of total triglycerides, total cholesterol, low‐density lipoprotein cholesterol, fasting blood glucose, and glycated hemoglobin, lower abdominal fat weight and abdominal fat index, increase levels of insulin and hepatic glycogen, and improve glucose tolerance and insulin sensitivity in diabetic rats. In addition, CY reduces oxidative stress and inflammation and reduces spleen weight and spleen index in diabetic rats. Notably, CY shows higher efficacy than RS in glucose tolerance and serum insulin and nitric oxide levels. This study suggests that CY powder may replace RS as a functional food in diabetic diets.

Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues.

To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice. The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5'-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis. HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone I, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology. C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM.

Garlic (Allium sativum L.) polysaccharide ameliorates type 2 diabetes mellitus (T2DM) via the regulation of hepatic glycogen metabolism

This study intends to explore the antihyperglycemic effect and the possible hypoglycemic mechanism of garlic (Allium sativum L.) polysaccharide (GP) using an animal model. Kunming mice were fed with GP (1.25, 2.5, 5.0 g/kg‧bw) for five weeks after insulin resistance (IR) engendering by a high-oil-high-sugar diet and streptozotocin (STZ). Intragastric administration of GP effectively improved the disease of polyphagia and polydipsia in diabetic mice. The fasting blood glucose (FBG) in the high-dose GP (DGH) group was meaningfully 42% lower than that in the diabetic model (DC) group showing its hypoglycemic effect. GP might manipulate hepatic glycogen metabolism by regulating the content of glucokinase (GK), glycogen synthase (GS), and phosphoenolpyruvate carboxykinase (PEPCK). Results showed that GP with a low relative molecular weight (MW) of 2.0 kDa consisted predominately of a 2,1-β-D-Fruf backbone with 20.7% side chains owning the structure-effect on hypoglycemia indicating it could be a potential supplement for the intervention and management of hyperglycemia.

Effect and mechanism of Buyang Huanwu decoction on retinal inflammation in streptozotocin-induced diabetic rats

ObjectiveTo observe the protective effect of Buyang Huanwu decoction (BYHWD) against retinal inflammation in diabetic rats. MethodsHealthy male Wistar rats were randomly divided into normal and diabetic model groups. Diabetic rats were given a one-time intraperitoneal injection of streptozotocin (STZ) to establish a diabetic phenotype and were randomly assigned to the negative control (saline), positive control (calcium dobesilate), and BYHWD treatment groups. After 8 weeks of treatment, fluorescein-labeled dextran and Evans blue dye were injected into the tail vein to observe vascular permeability and vascular leakage in the retina, respectively. Perfusion of fluorescein-labeled concanavalin was used to detect adhesion in rat retinal leukocytes. Western blotting was used to quantify the expression levels of the inflammatory factors TNF-α, NF-κBp65, and p-NF-κBp65 in retinal tissue. ResultsCompared with nondiabetic rats, saline-treated diabetic rats showed significantly increased retinal vascular leakage, leukocyte adhesion, and protein levels of TNF-α and p-NF-κBp65 (P<0.05). These effects were significantly reduced in the positive control and BYHWD groups (P<0.05). ConclusionBuyang Huanwu decoction can ameliorate retinal inflammation in STZ-induced diabetic rats. Its mechanism of action may be related to the inhibition of TNF-α expression and NF-κB pathway activation.

KLF15/mTOR related proteins involved in effect of aerobic interval training on improving skeletal muscle lesions in rats with type 2 diabetes

Objective: To investigate the effects of aerobic intermittent exercise on the expressions of KLF15/mTOR related proteins to improve skeletal muscle lesions in type 2 diabetes rats. Methods: The experimental model of type 2 diabetes rats was established by feeding high-fat diet for 4 weeks and intraperitoneal injection of streptozotocin (STZ). After modeling, rats were randomly divided into two groups: diabetes model group (DM), diabetes+exercise group (DE), and normal rats were set as control group (C), 10 rats in each group. Group DE was given 8-week aerobic intermittent treadmill exercise intervention, while group C was not given any intervention. At the end of the experiment, the expressions of KLF15, mTOR, p-mTOR, and cleared caspase-3 in gastrocnemius muscle were detected by Western blot. The histopathologic changes of gastrocnemius were observed under microscope; skeletal muscle cells apoptosis rates and muscle mass were examined respectively using HE staining and TUNEL fluorescence staining. At the same time, changes of blood glucose and serum insulin, and weight were examined in the end of the experiment. Results: ①Compared with group C, the wet weight of gastrocnemius muscle and body weight, ratio of wet gastrocnemius muscle and body weight in group DM were decreased(P＜0.05 or P＜0.01); compared with group DM, the wet weight of gastrocnemius muscle, ratio of wet gastrocnemius muscle and body weight in the group DE were increased significantly (P＜0.05). ②Compared with group C, the fasting blood glucose level of group DM was increased significantly (P＜0.01), while serum insulin level of the group DM was decreased significantly(P＜0.01);compared with group DM, the above indexes were opposite in the group DE with intervention(P＜0.05). ③Compared with group C, the morphology of skeletal muscle cells in group DM was abnormal, the number of muscle nuclei was increased, the transverse lines were blurred and disappeared, the sarcomere was broken, and some muscle fibers were dissolved. Compared with group DM, the abnormal cell morphology, segmental injury of sarcomere and dissolution of muscle fibers in group DE were improved. The sarcolemma was more complete and the arrangement of muscle nuclei was more orderly. ④Compared with group C, the expressions of KLF15 and cleaved caspase-3, cells apoptosis rates in group DM were increased significantly(P＜0.01), while p-mTOR/mTOR level was decreased(P＜0.01) ; compared with group DM, the above indexes were opposite in the group with intervention(P＜0.05 or P＜0.01). Conclusion: Aerobic intermittent exercise is beneficial to improve the skeletal muscle pathological changes in type 2 diabetes rats, which may be due to the effective regulation of KLF15/mTOR related protein expression and the reduction of apoptosis damage.

DIFFERENCES IN OSTEOBLAST COUNT AND ITS EFFECT ON ORTHODONTIC MOVEMENT OF DIABETIC MODELS’ TEETH AFTER ORAL ADMINISTRATION OF OLIVE OIL

Background: In patients with uncontrolled diabetes, an increase in Advanced glycation end products (AGEs) inhibits osteoblast differentiation so that the number of osteoblasts decreases and interferes with bone formation in orthodontic movement. Giving natural ingredients such as olive oil is proven to increase the number of osteoblasts. Purpose: To determine differences in the number of osteoblasts and their effect on the orthodontic movement of diabetic teeth after oral administration of olive oil. Method: 25 male guinea pigs divided into four groups: diabetic guinea pigs treated with olive oil at a dose of 0.7; 1.05; 1.4 ml/day, distilled water, and healthy guinea pigs were given aquadest. Alveolar bone tissue samples were taken on the 15th day after orthodontic application, and then the number of osteoblasts was calculated histologically. Result: In the diabetic model group treated with olive oil doses of 0.7; 1.05; 1.4 ml/day, distilled water, and healthy guinea pigs given aquades were 2.900 ± 0.678; 4.320 ± 0.497; 5.920 ± 0. 460; 0.200 ± 0.200; 1.320 ± 0.415. The study showed that the olive oil treatment group had more osteoblasts than the untreated group. Analysis one way ANOVA showed a very significant difference between the treatment group and the untreated group (p≤0.01), while the LSD test showed a significant difference between groups. The highest number of osteoblasts was found at a dose of 1.4 ml/day. Conclusion: There was an increase in osteoblasts in the orthodontic movement of diabetic teeth after oral administration of olive oil.

ANTI-INFLAMMATORY EFFECTS OF Channa micropeltes EXTRACT TOWARDS INTERLEUKIN-10 IN DIABETIC RAT

Background: Inhibition of tissue repair is a symptom of prolonged diabetic inflammation that occurs in wounds resulting in delayed healing. Inflammation can be controlled by giving food supplements that have anti-inflammatory properties such as Channa micropeltes (CM). CM has high protein content, including albumin, omega 3 and omega 6 fatty acids, vitamin C, and zinc. Purpose: This study aimed to analyse the effect of the CM extract on the levels of IL-10 in the wound healing process of normal and diabetic rats. Methods: This study was a true experimental design with a post-test-only control group design. The samples were the diabetic model group given CM extract at 16 mL/kg BB dose and negative control group for 14 days. Results: Compared to the control, the concentration of IL-10 in DM group was significantly higher in the DM without CM treatment. Interestingly, we found the level of IL-10 in DM-CM was significantly decreased while the level of TNF-a in DM-CM decreased as well. Conclusion: CM at a dose of 16 mL/kg BW for 14 days in the wound healing process of Wistar rats can increase IL-10 in the normal group but could not increase IL-10 in the diabetic group. Keywords: Anti-inflammatory, Channa micropeltes, Diabetes, Interleukin-10.

Evaluation of Hypoglycemic Activity and Sub-Acute Toxicity of the Novel Biochanin A-Chromium(III) Complex.

The novel biochanin A–chromium(III) complex was synthesized by chelating chromium with biochanin A (BCA). The structure of the complex was determined and the complex ([CrBCA3]) was composed of chromium(III) and three ligands, and the chromium content was 55 μg/mg. The hypoglycemic activity of the complex was studied in db/db mice and C57 mice. The sub-acute toxicity test of the complex was carried out by the maximum limit method in KM mice. The hypoglycemic activity showed that the complex could reduce the weight of db/db mice and lower the fasting blood glucose and random blood glucose levels. The complex also improved the organ index, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results of db/db mice, and some of the indicators were similar to those of the positive control group after treatment with the complex. The histopathology study showed significant improvements in the liver, kidney, pancreas and skeletal muscle compared with the diabetes model group. The complex also showed a significant improvement in serum biochemical indices and antioxidant enzyme activities, as well as glycogen levels. The sub-acute toxicity study showed that the complex did not cause death or any dangerous symptoms during the study. In addition, the sub-acute toxicity study showed that the complex had no significant effect on the serum biochemical indices, antioxidant capacity and organs of normal mice. This study showed that [CrBCA3] had good hypoglycemic activity in vivo and had no sub-acute toxicity. This work provides an important reference for the development of functional hypoglycemic foods or drugs.

Dapagliflozin Improves Diabetic Cardiomyopathy by Modulating the Akt/mTOR Signaling Pathway.

Background Dapagliflozin can significantly improve heart failure, and Cx43 is one of the molecular mechanisms of heart failure. This study investigated the effect of dapagliflozin on Cx43 and Akt/mTOR signaling pathway in ventricular myocytes. Methods A rat model of type 2 diabetes mellitus was established by high-fat diet combined with streptozotocin, and the animals were treated randomly with dapagliflozin. The morphological changes of the myocardium were observed by hematoxylin eosin staining, and the expression and distribution of Cx43 in ventricular myocytes were detected by immunohistochemistry. And Western blot determined the expressions of Cx43, Akt, mTOR, p62, and LC3 proteins in rat myocardium. Results Compared with the normal control group, the heart rate of diabetic rats decreased significantly (p < 0.05), QRS wave of ECG widened, and QT interval prolonged (p < 0.05). Dapagliflozin treatment in diabetic rats resulted in improvements in these ECG indexes (p < 0.05) with early administration group obtaining greater efficacy than the late administration group (p < 0.05). In the normal control group, the cardiomyocytes were arranged orderly, and the expression of Cx43 was dense, uniform, and regular, which was higher than that in the intercalated disc. In the diabetic control model group, the cardiomyocytes were enlarged and presented disorderly with detection of Cx43 in the cytoplasm. Early use of dapagliflozin better improved these myocardial tissue lesions. Of note, as diabetic rats exhibited decreased expression of Cx43, Akt, and mTOR (p < 0.05), increased p62 expression (p < 0.05), and decreased LC3-II/I ratio (p < 0.05), administration of dapagliflozin partially reversed the expression of the above proteins (p < 0.05) with greater improvement in the early administration group compared with the late administration group (p < 0.05). Conclusions Dapagliflozin increases the expression of Cx43 in cardiomyocytes of diabetic rats and thereby alleviates heart failure partly through regulating the Akt/mTOR signaling pathway.

Metformin Improves the Senescence of Renal Tubular Epithelial Cells in a High-Glucose State Through E2F1.

Diabetic kidney disease is a major cause of chronic kidney condition and the most common complication of diabetes. The cellular senescence participates in the process of diabetic kidney disease, but the specific mechanism is not yet clear. Cell cycle-related protein E2F transcription factor 1 (E2F1) is a member of the E2F transcription factor family, it plays a key role in cellular damage under HG conditions. In this study, we explored whether metformin improves a high-glucose-induced senescence and fibrosis of renal tubular epithelial cells through cell cycle-related protein E2F1. In the in vivo experiments, the recombinant adeno-associated virus (AAV-shE2F1) knockdown E2F1 gene was injected into the tail vein of 16-weeks-old db/db mice for 8 weeks. The 16-week-old db/db mice were administered metformin (260 mg/kg/d) continuously for 8 weeks. The normal control group (NC) and diabetic model group (DM) were set up simultaneously. Mice renal tubular epithelial cells (mRTECs) were cultured in vitro. The cells were randomly divided into the following groups: normal glucose (NG, containing 5.5 mmol/L glucose), high glucose group (HG, containing 30 mmol/L glucose), NG/HG metformin intervention group (NG/HG + Met), NG/HG negative control siRNA transfection group (NG/HG + Control), NG/HG E2F1 siRNA transfection group (NG/HG + siRNA E2F1), HG metformin intervention and overexpression E2F1 plasmid transfection group (HG + Met + overexpress-E2F1). The expression of related indexes were detected by Western blot, real-time polymerase chain reaction (PCR), immunohistochemistry, and immunofluorescence. The results showed that E2F1 knockdown or metformin reduces the degree of renal fibrosis, DNA damage, and cellular senescence in the DM group; metformin also reduced the expression of E2F1. If E2F1 was overexpressed, the effects of metformin in delaying fibrosis and reducing DNA damage and cellular senescence could be weakened. Thus, metformin alleviates high-glucose-induced senescence and fibrosis of renal tubular epithelial cells by downregulating the expression of E2F1.

Jiangtang Tongmai Prescription Reduced Diabetic Lung Injury Through SnoN and TGF-β1/Smads Signaling Pathway.

By establishing a rat diabetes model in rats with intervening treatment by Jiangtang Tongmai Prescription (JTTMP), this study explored the restorative pairing effect of JTTMP on diabetic lung injury. The model of type II diabetes model was used to establish the rat diabetes model, using a high-fat diet and streptozotocin (STZ) induction. Different doses of JTTMP and metformin were administered as a therapeutic to intervene, and blood was collected to assess the blood glucose level of each group of rats. HE (Hematoxylin and eosin (H&E) staining was performed to detect the morphological changes in rat lung tissue and enzyme-linked immunoassay ELISA was used to detect and quantify the expression of interleukin (IL)-6, TNF tumor necrosis factor-ɑa, and IL-1β in serum and the lung tissue of each group of rats. The level expression of TGF-β1 [transforming growth factor (TGF)-β1), SnoN (transcriptional co-repressor Ski-N terminal (SnoN)], Smad2, Smad3, Smad7, and other signaling pathway proteins were assessed by Western blot. In comparison with the normal control (NC) group, rats in the diabetes model (DM) group lost weight and showed significantly increased blood sugar levels. The levels of TGF-β1 and Smad2/3 were increased in the DM group but Smad7 decreased. After 8 weeks of JTTMP intervention, the level of TGF-β1 and Smad2/3 decreased but Smad7 increased, blood sugar decreased significantly and the expression of inflammatory factors in lung tissue decreased. Therefore, JTTMP may activate SnoN and the downstream TGF-β1/Smads signaling pathway to repair diabetic lung injury, which suggests its application has potential for future clinical treatment of diabetes with lung injury.