Reduced Fasting Blood Glucose Levels Research Articles

MiRNA-133a-3p Attenuates Renal Tubular Epithelial Cell Injury via Targeting MALM1 and Suppressing the Notch Signaling Pathway in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes characterized by structural and functional changes of kidneys. Human renal tubular epithelial (HK-2) cells are important for kidney recovery post injury and usually used for establishment of DN cell models. The study explored the role of microRNA (miR)-133a-3p in DN cell model and animal model. A cell model for DN was established via high glucose (HG) stimulation to HK-2 cells. Cell viability and apoptotic rate were measured by cell counting kit 8 and flow cytometry. Polymerase chain reaction was performed to quantify levels of miR-133a-3p and targets. Luciferase reporter assay was conducted to verify the binding of miR-133a-3p and MAML1. After establishment of a mouse model of DN, levels of renal function indicators were measured by biochemical analysis. Hematoxylin-eosin and periodic acid-schiff staining of kidney samples were performed to analyze histological changes. Western blotting was conducted to quantify levels of apoptotic markers, MAML1, and factors related to Notch signaling. Results showed that HG induced HK-2 cell apoptosis and the reduction of cell viability. MiR-133a-3p was lowly expressed in HG-stimulated HK-2 cells. Overexpressed miR-133a-3p improved HK-2 cell injury by increasing cell viability and hampering apoptosis under HG condition. In addition, miR-133a-3p directly targets MAML1 3'-untranslated region. MAML1 overexpression countervailed the repressive impact of miR-133a-3p on cell apoptosis in the context of HG. Moreover, miR-133a-3p inhibited the activity of Notch pathway by downregulating MAML1. MiR-133a-3p inhibits DN progression in mice, as evidenced by reduced fasting blood glucose level, improved levels of renal function parameters, and alleviation of kidney atrophy. In conclusion, miR-133a-3p improves HG-induced HK-2 cell injury and inhibits DN progression by targeting MAML1 and inactivating Notch signaling.

Integrated network pharmacology and pharmacological investigations to discover the active compounds of Toona sinensis pericarps against diabetic nephropathy

Ethnopharmacological relevanceToona sinensis (A. Juss.) Roem. Is a deciduous woody plant native to Eastern and Southeastern Asia. Different parts of this plant have a long history of being applied as traditional medicines to treat various diseases. The fruits have been used for antidiabetic, antidiabetic nephropathy (anti-DN), antioxidant, anti-inflammatory, and other activities. Aim of the studyThe purpose of this study was to investigate the effects of EtOAc (PEAE) and n-BuOH extracts (PNBE) from T. sinensis pericarps (TSP) on kidney injury in high-fat and high-glucose diet (HFD)/streptozotocin (STZ)-induced DN mice by network pharmacology and pharmacological investigations, as well as to further discover active compounds that could ameliorate oxidative stress and inflammation, thereby delaying DN progression by regulating the Nrf2/NF-κB pathway in high glucose (HG)-induced glomerular mesangial cells (GMCs). Materials and methodsThe targets of TSP 1–16 with DN were analyzed by network pharmacology. HFD/STZ-induced DN mouse models were established to evaluate the effects of PEAE and PNBE. Six groups were divided into normal, model, PEAE100, PEAE400, PNBE100, and PNBE400 groups. Fasting blood glucose (FBG) levels, organ indices, plasma MDA, SOD, TNF-α, and IL-6 levels, as well as renal tissue Nrf2, HO-1, NF-κB, TNF-α, and TGF-β1 levels were determined, along with hematoxylin-eosin (H&E) and immunohistochemical (IHC) analysis of kidney sections. Furthermore, GMC activity screening combined with molecular docking was utilized to discover active compounds targeting HO-1, TNF-α, and IL-6. Moreover, western blotting assays were performed to validate the mechanism of Nrf2 and NF-κB in HG-induced GMCs. ResultsNetwork pharmacology predicted that the main targets of PEAE and PNBE in the treatment of DN include IL-6, INS, TNF, ALB, GAPDH, IL-1β, TP53, EGFR, and CASP3. Additionally, major pathways include AGE-RAGE and IL-17. In vivo experiments, treatment with PEAE and PNBE effectively reduced FBG levels and organ indices, while plasma MDA, SOD, TNF-α, and IL-6 levels, renal tissue Nrf2, HO-1, NF-κB, TNF-α, and TGF-β1 levels, and renal function were significantly improved. PEAE and PNBE significantly improved glomerular and tubule injury, and inhibited the development of DN by regulating the levels of oxidative stress and inflammation-related factors. In vitro experiments, compound 11 strongly activated HO-1 and inhibited TNF-α and IL-6. The molecular docking results revealed that compound 11 exhibited a high binding affinity towards the targets HO-1, TNF-α, and IL-6 (<−6 kcal/mol). Western blotting results showed compound 11 effectively regulated Nrf2 and NF-κB p65 protein levels, and significantly improved oxidative stress damage and inflammatory responses in HG-induced GMCs. ConclusionPEAE, PNBE, and their compounds, especially compound 11, may have the potential to prevent and treat DN, and are promising natural nephroprotective agents.

Effectiveness of switching from first-generation basal insulin to Glargine 300 U/mL in children and adolescents with type 1 diabetes: results from the ISPED CARD database.

Glargine 300 U/mL (Gla-300) has been recently approved for use in children and adolescents with type 1 diabetes (T1D). However, real-world effectiveness data are scarce, and aim of this analysis was to assess clinical outcomes in young patients with T1D switching from 1st generation basal insulin (1BI) to Gla-300. ISPED CARD is a retrospective, multicenter study, based on data anonymously extracted from Electronic Medical Records. The study involved a network of 20 pediatric diabetes centers. Data on all patients aged < 18years with T1D switching from 1BI to Gla-300 were analyzed to assess clinical characteristics at the switch and changes after 6 and 12months in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and standardized body mass index (BMI/SDS). Titration of basal and short-acting insulin doses was also evaluated. Overall, 200 patients were identified. The mean age at the switch to Gla-300 was 13years, and mean duration of diabetes was 3.9years. Average HbA1c levels at switch were 8.8%. After 6months, HbA1c levels decreased by - 0.88% (95% CI - 1.28; - 0.48; p < 0.0001). The benefit was maintained after 12months from the switch (mean reduction of HbA1c levels - 0.80%, 95% CI - 1.25; - 0.35, p = 0.0006). Trends of reduction in FBG levels were also evidenced both at 6months and 12months. No significant changes in short-acting and basal insulin doses were documented. The study provides the first real-world evidence of the effectiveness of Gla-300 in children and adolescents with T1D previously treated with 1BI. The benefits in terms of HbA1c levels reduction were substantial, and sustained after 12months. Additional benefits can be expected by improving the titration of insulin doses.

Both High-Intensity Interval and Moderate-Intensity Continuous Training Decrease Fetuin-A Levels in High Fat Diet Fed Male Rats

Background: Fetuin-A is a hepatokine that increases in obesity, and a high-fat diet (HFD) contributes to this condition. Obesity is characterized by increased body mass index (BMI) and is correlated to insulin resistance. This study aims to analyze the difference between High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) on fetuin-A, insulin, fasting blood glucose (FBG) levels, and BMI in HFD-fed rats. Methods: Twenty-four male Wistar rats were divided into four groups: CD (standard diet), HFD (HFD only), HFD-IT (HFD and HIIT), and HFD-CT (HFD and MICT). HFD consisted of a standard diet with an additional 2 mL/200-gram body weight of lard oil daily. In the HFD-IT group, swimming was performed with a 9% body weight load with short duration and intermittent rest periods, while the HFD-CT group was given a 6% body weight load and continuous swimming. Swimming was conducted five days a week for four weeks. Fetuin-A and insulin levels were measured using enzyme-linked immunosorbent assay (ELISA) method, and FBG levels were measured using a glucometer. Results: Fetuin-A levels were significantly lower in the HFD-IT and HFD-CT groups compared to the HFD group (p&lt;0.05). The HFD-CT group had a significant decrease in FBG levels (p&lt;0.05), but the HFD-IT group did not. There were no differences in BMI and insulin levels between groups after four weeks of treatment (p&gt;0.05). Conclusion: HIIT and MICT have similar effectiveness in reducing fetuin-A levels. In addition, MICT also managed to reduce FBG levels. Keywords: interval training, continuous training, high-fat diet, fetuin-A, insulin, healthy lifestyle.

1,3,4-Oxadiazole Scaffold in Antidiabetic Drug Discovery: An Overview.

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. With the increasing number of cases of diabetes and drug-resistant diabetes, there is an urgent need to develop new potent molecules capable of combating this cruel disease. Medicinal chemistry concerns the discovery, development, identification, and interpretation of the mode of action of biologically active compounds at the molecular level. Oxadiazole-based derivatives have come up as a potential option for antidiabetic drug research. Oxadiazole is a five-membered heterocyclic organic compound containing two nitrogen atoms and one oxygen atom in its ring. Oxadiazole hybrids have shown the ability to improve glucose tolerance, enhance insulin sensitivity, and reduce fasting blood glucose levels. The mechanisms underlying the antidiabetic effects of oxadiazole involve the modulation of molecular targets such as peroxisome proliferator-activated receptor gamma (PPARγ), α-glucosidase, α-amylase and GSK-3β which regulate glucose metabolism and insulin secretion. The present review article describes the chemical structure and properties of oxadiazoles and highlights the antidiabetic activity through action on different targets. The SAR for the oxadiazole hybrids has been discussed in this article, which will pave the way for the design and development of new 1,3,4-oxadiazole derivatives as promising antidiabetic agents in the future. We expect that this article will provide comprehensive knowledge and current innovation on oxadiazole derivatives with antidiabetic potential and will fulfil the needs of the scientific community in designing and developing efficacious antidiabetic agents.

Bioinformatic analysis and construction of competitive endogenous RNA network reveals protective effect of Jiangtang Sanhao Formula on the liver of diabetic mice

IntroductionJiangtang Sanhao Formula (JTSHF), composed of Panax ginseng, Atractylodes macrocephala, Coptis chinensis, Salvia miltiorrhiza and several other herbs, is a traditional Chinese medicine formula commonly used to treat type 2 diabetes. This compound shows significant clinical efficacy in the treatment of diabetic, however, its target and pharmacological mechanism are still unclear. The present study explored the therapeutic effect of JTSHF on diabetic mice and conducted RNA sequencing to investigate the potential mechanism. MethodsThe T2DM mice model was established using a high-fat diet combined with an intraperitoneal injection of low-dose STZ. Fasting blood glucose (FBG), serum insulin, glucose tolerance, and blood lipids in mice from different groups were examined. Then the effects of JTSHF on oxidative stress and liver histopathology in diabetic mice were observed. Next, transcriptome analysis was performed to identify differentially expressed genes (DEG), which were validated using real-time quantitative PCR (RT-qPCR). By using pathway enrichment analysis, we identified several key pathways which are essential in the JTSHF effect on T2DM. Finally, we constructed ceRNA network to illustrate the regulatory effect of JTSHF on transcriptional profile in diabetic liver. ResultsJTSHF reduced FBG level and blood lipid contents, ameliorated glucose tolerance and improved insulin sensitivity in diabetic mice. It also showed protective effects on fatty livers induced by high-fat diet and diabetes. For the first time, we revealed that JTSHF exerts anti-T2DM role in the liver of diabetic mice, which is associated with multiple molecular targets and signaling pathways. Enrichment analysis and treatment-based mRNA-ncRNA-miRNA ceRNA networks revealed that JTSHF might exerts therapeutic effect by modulating lipid metabolism. DiscussionOur research found that JTSHF exerts anti-T2DM effect by affecting multiple pathways. Among these, lipid metabolism and oxidative stress might be involved. The present study provided novel insights for the mechanism of JTSHF, and the differentially expressed genes identified can be potential therapeutic targets in the treatment of T2DM in future.

A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids.

Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE). The effects of PHE on body weight (BW), fasting blood glucose (FBG) level, gut microbiota, fecal short-chain fatty acids (SCFAs) production, and the correlation between DM-related indices and gut microbes, in rats were investigated. Chebulic acid (0.368%), gallic acid (0.469%), andrographolide (1.304%), berberine (6.442%), and numerous polysaccharides were the most representative constituents in PHE. A more significant BW gain and a reduction in FBG level towards normal of PHE 600mg/kg treated rats group were resulted at the end of 28th days of the study. Moreover, the composition of the gut microbiota corroborated the study's hypothesis, as evidenced by an increased ratio of Bacteroidetes to Firmicutes and some beneficial microbial species, including Prevotella copri and Lactobacillus hamster. The relative abundance of Bifidobacterium pseudolongum, Ruminococcus bromii, and Blautia producta was found to decline in PHE treatment groups as compared to diabetic group. The abundance of beneficial bacteria in PHE 600mg/kg treatment group was concurrently associated with increased SCFAs concentrations of acetate and propionate (7.26nmol/g and 4.13nmol/g). The findings of this study suggest a promising approach to prevent DM by demonstrating that these naturally occurring compounds decreased FBG levels by increasing SCFAs content and SCFAs producing gut microbiota.

S-9-PAHSA's neuroprotective effect mediated by CAIII suppresses apoptosis and oxidative stress in a mouse model of type 2 diabetes.

With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. This invivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an invitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in invivo and invitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.

Yam Gruel alone and in combination with metformin regulates hepatic lipid metabolism disorders in a diabetic rat model by activating the AMPK/ACC/CPT-1 pathway

BackgroundAs independent and correctable risk factors, disturbances in lipid metabolism are significantly associated with type 2 diabetes mellitus (T2DM). This research investigated the mechanism underlying the lipid-regulating effects of Yam Gruel in diabetic rats.MethodsFirst, rats in the control group were given a normal diet, and a diabetic rat model was established via the consumption of a diet that was rich in both fat and sugar for six weeks followed by the intraperitoneal injection of streptozotocin (STZ). After the model was established, the rats were divided into five distinct groups: the control group, model group, Yam Gruel (SYZ) group, metformin (MET) group, and combined group; each treatment was administered for six weeks. The fasting blood glucose (FBG), body and liver weights as well as liver index of the rats were determined. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartic acid transaminase (AST), alanine aminotransferase (ALT), and nonesterified fatty acid (NEFA) levels were measured. Oil Red O staining was used to assess hepatic steatosis. In addition, the levels of Phospho-acetyl-CoA carboxylase (p-ACC), acetyl coenzyme A carboxylase (ACC), AMP-activated protein kinase (AMPK), Phospho-AMPK (p-AMPK), carnitine palmitoyl transferase I (CPT-1), and Malonyl-CoA decarboxylase (MLYCD) in liver tissues were measured by real-time PCR (q-PCR) and western blotting.ResultsAfter 6 weeks of treatment, Yam Gruel alone or in combination with metformin significantly reduced FBG level, liver weight and index. The concentrations of lipid indices (TG, TC, NEFA, and LDL-C), the levels of liver function indices (ALT and AST) and the degree of hepatic steatosis was improved in diabetic rats that were treated with Yam Gruel with or without metformin. Furthermore, Yam Gruel increased the protein levels of p-ACC/ACC, p-AMPK/AMPK, MLYCD, and CPT-1, which was consistent with the observed changes in gene expression. Additionally, the combination of these two agents was significantly more effective in upregulating the expression of AMPK pathway-related genes and proteins.ConclusionsThese results demonstrated that Yam Gruel may be a potential diet therapy for improving lipid metabolism in T2DM patients and that it may exert its effects via AMPK/ACC/CPT-1 pathway activation. In some respects, the combination of Yam Gruel and metformin exerted more benefits effects than Yam Gruel alone.

Comparison of the anti-diabetic effects of various grain and legume extracts in high-fat diet and streptozotocin-nicotinamide-induced diabetic rats

The anti-diabetic properties of whole groats and dietary fibers from various grains and legumes are well known. Nevertheless, studies on the anti-diabetic effects of their extracts are limited, and it is difficult to compare their efficacy. This study investigated the anti-diabetic potential of ethanol extracts from oats (OE), sorghum (SE), foxtail millet (FE), proso millet (PE), adzuki bean (AE), and black soybean (BE) in a high-fat diet and streptozotocin-nicotinamide-induced diabetic rat models. The extracts, obtained using 99.9 % ethanol, were orally administered to diabetic rats for four weeks. Various parameters were evaluated, including fasting blood glucose levels, glucose tolerance, insulin sensitivity, serum insulin levels, and pancreas histological analysis. OE and SE effectively reduced fasting blood glucose levels and the area under the curve (AUC) in the oral glucose tolerance test. Only OE significantly decreased the AUC in the insulin tolerance test and increased insulin concentration and homeostatic model assessment of the β-cell function index, indicating improved insulin sensitivity and β-cell function. Histological and immunohistochemical analysis of the pancreas supported these findings, demonstrating that OE protected against pancreatic cell damage. In contrast, FE, PE, AE, and BE did not have a significant effect on diabetes-related parameters. These findings identify OE as the most promising natural intervention for diabetes management.

Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice

AbstractGCG ((−)‐gallocatechin gallate) and EGCG ((−)‐epigallocatechin‐3‐gallate) are main biologically active polyphenolic compounds in tea leaves, and EGCG has been studied for its potential effects on alleviating diabetic nephropathy (DN). Previous studies showed that GCG exhibited better hypoglycemic and antioxidant efficacy than EGCG. However, the efficacy and molecular mechanisms of GCG in the protection of DN are unknown. In this study, db/db mice were administered with EGCG or GCG orally for 20 weeks to comparatively investigate their effects on DN. These results revealed that GCG was significantly more effective than EGCG in decreasing water intake and urine excretion, reducing fasting blood glucose levels and systolic blood pressure, improving mesenteric artery contractility, enhancing the right renal hemodynamics, and improving key renal function markers. Through transcriptome analysis, S100A8/S100A9, two regulators of interstitial fibrosis, were identified and found to be more sensitive to GCG intervention, which was further confirmed by mRNA and protein expression data. In addition, the molecular docking analysis results demonstrated that GCG displayed a superior binding affinity toward S100A8/S100A9 in comparison to EGCG. Overall, our study found that GCG holds significant potential for the treatment of DN and outperforms EGCG in terms of efficacy.

Puerarin alleviates diabetic nephropathy by inhibiting Caspase-1-mediated pyroptosis.

Diabetic nephropathy (DN) is an important cause of end-stage renal disease, with podocyte injury as the main feature. Pyroptosis plays a non-negligible role in the process of diabetic nephropathy. Puerarin (PR) treatment of diabetic nephropathy has great potential, but the mechanism is not very clear. This article aims to study the protective effect and mechanism of puerarin on DN. Streptozotocin (STZ)-induced C57 BL/6J mouse model of DN was given PR, Necrosulfomide (NSA), Nigericin for 12 weeks; A 60 mM high glucose(HG) induced MPC5 cell injury model was administered to PR, NSA, and Nigericin interventions for 24 h. After 12 weeks of administration, PR reduced fasting blood glucose levels in DN mice, alleviated glomerular lesions, reduced podocyte damage, and protected renal function. Meanwhile, PR also inhibits the expression of pyroptosis-related proteins. In addition, PR alleviated the release of Interleukin 18 (IL-18), Interleukin 1beta (IL-1β), and lactate dehydrogenase (LDH) in MPC5 cells under HG conditions, downregulated the expression of pyrozozois-related proteins, and improved Caspase-1-mediated pyroptosis in MPC5 cells. Our study suggests that the beneficial effects of PR in diabetic nephropathy may be associated with inhibition of Caspase-1-mediated pyroptosis.

Alpha-glucosidase inhibitory and hypoglycemic effects of imidazole-bearing thioquinoline derivatives with different substituents: In silico, in vitro, and in vivo evaluations

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC50 = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with Ki = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health.

Laminaria japonica polysaccharide alleviates type 2 diabetes by regulating the microbiota-gut-liver axis: A multi-omics mechanistic analysis

The hypoglycemic effects of low-molecular-weight Laminaria japonica polysaccharide (LJO) were investigated in type 2 diabetes mellitus (T2DM) mice, focusing on its effect on the microbiome, metabolome, and transcriptome. The findings demonstrated that LJO significantly reduced fasting blood glucose levels, insulin levels, and inflammatory factors. Additionally, LJO induced changes in gut microbiota composition and increased the concentrations of cecal short-chain fatty acids. Analysis of transcriptomics and metabolomics data revealed that LJO primarily altered the endocrine and digestive systems, signal transduction, and lipid metabolism. It led to a decrease in palmitic acid levels and an increase in glutathione levels. Real-time quantitative polymerase chain reaction assay suggested that LJO upregulated Irs1 expression, consequently reducing insulin resistance. These findings strongly suggest that LJO holds promise in ameliorating T2DM and may serve as a potential dietary supplement for patients with T2DM.

Effect of Buffalo Curd Milk-Edamame Pudding Snack Consumption on Fasting Blood Glucose Levels and Lipid Profile in Diabetes Mellitus Patients

Background: Buffalo milk curd, a native probiotic source from Indonesia, is dominated by live indigenous Lactic Acid Bacteria known for their ability to lower blood glucose levels. Edamame contains amino acid arginine, chromium, antioxidants, and fibre, aiding in blood glucose control and lipid profile reduction. Objectives: This study aimed to assess the effects of buffalo milk curd and edamame-based pudding snacks on fasting blood glucose levels and lipid profiles in Type 2 diabetes mellitus (T2DM) patients. Methods: This study used a True Experiment Design with Pretest-Posttest Control Group Design. The study involved 32 patients divided into treatment and control groups. During the study, the treatment group received 250 g of snacks in the morning and evening for one week. Blood glucose levels and lipid profiles were measured using the enzymatic colourimetry method. Results: The results showed decreased fasting blood glucose levels before and after treatment in both control (-17.06 ± 40.17) and treatment (-48.38 ± 40.27 mg/dl) groups (p=0.036). Total cholesterol levels also decreased in control (-15.87 ± 23) and treatment (-41.4 ± 19 mg/dl) groups (p=0.001). There were decreased LDL levels in control (-6.81 ± 29.09) and treatment (-27.3 ± 25.09 mg/dl) groups (p=0.04). However, HDL and TG levels showed no differences at the end of the study. Conclusions: Buffalo curd milk-edamame pudding snacks can reduce fasting blood glucose levels and lipid profiles, particularly total cholesterol and LDL levels, in Type 2 DM patients.

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

Glomerulosclerosis and tubulointerstitial fibrosis (TIF) are closely involved in the development of diabetic nephropathy (DN). Moreover, the development of TIF is closely related to epithelial-to-mesenchymal transition (EMT). Tanshinone IIA (Tan) has various pharmacological effects, especially the anti-fibrotic effect. And it is mainly used in the clinical treatment of cardiovascular diseases. Currently, the protective effect of Tan on DN and its possible mechanism have not been clearly elucidated. Our previous studies illustrated that Tan could improve the EMT of HK-2 cells induced by high glucose by regulating the vitamin D receptor (VDR)/Wnt/β-catenin pathway. Here, we collected demographic information and laboratory results from the National Health and Nutrition Examination Survey (NHANES) database in order to investigate the relationship between VD and DN. Then, we established a DN model and treated DN rats with Tan and paricalcitol (Par) for 6 weeks. We subsequently compared the changes in general condition, renal function, pathological changes, and TIF-related protein expression levels of control rats, DN rats induced by STZ, DN rats with Tan at 5.4 mg/kg, DN rats with Tan at 10.8 mg/kg, and DN rats with Par at 0.054 µg/kg, to explore the effect and mechanism of Tan and Par on DN rats. The results showed that VD had a protective effect against DN in diabetic patients. And we found that Tan had a protective effect on renal fibrosis in DN rats, which was superior to Par in improving the symptoms of “three more and one less,” reducing fasting blood glucose level, improving renal index, BUN/SCr, and UACR, reducing histopathological damage of kidney, and improving the expression of fibrosis-related proteins in kidney tissue by regulating VDR/Wnt/β-catenin pathway. Tan was superior to Par in ameliorating tubulointerstitial fibrosis by regulating VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy.

Effects of ginseng peptides on the hypoglycemic activity and gut microbiota of a type 2 diabetes mellitus mice model

Ginseng peptide (GP) (100, 200, 400 mg/kg bw) lowered blood glucose levels, explored the relationship between GP and gut microbiota-based hypoglycemic effects. GP significantly reduced fasting blood glucose levels (25.38–13.37 mM), improved insulin resistance (IR) (9.78–5.02), considerably increased liver glycogen content (64.71–97.95 mg/g), glycolytic and gluconeogenesis enzyme activities in T2DM mice, significantly reduced free fatty acids (1.65–0.93 mM), triglycerides (1.55–0.66 mM), total cholesterol (14.75–5.43 mM), and low-density lipoprotein (4.12–2.36 mM) in the serum, significantly increased high-density lipoprotein levels (6.20–17.44 mM) to improve lipid metabolism disorders. According to colonic 16S rDNA sequencing results, GP-H regulated gut microbiota disorders and short chain fatty acid metabolism. Western blot analysis showed that GP could regulate glycogen synthesis, gluconeogenesis, and glucose transport by activating IRS-1/PI3K/Akt and AMPK signaling pathways and improve IR by inhibiting the mitochondrial apoptosis signaling pathway.

Ameliorative effects of Scutellaria Pinnatifida subsp. pichleri (Stapf) Rech.f. Extract in streptozotocin-induced diabetic rats: chemical composition, biochemical and histopathological evaluation

BackgroundsScutellaria Pinnatifida subsp. pichleri (Stapf) Rech.f. (SP) is used in folk medicine for the treatment of diabetes. The aim of the study was to determine the phenolic profile of SP extract (SPE) by LC-MS/MS and to investigate the antidiabetic, hepatoprotective and nephroprotective effects of SPE in streptozotosin (STZ)-induced diabetic rat model.MethodsForty-two rats were randomly divided into six groups (n = 7): Control (nondiabetic), diabetes mellitus (DM), DM + SP-100 (diabetic rats treated with SPE, 100 mg/kg/day), DM + SP-200 (diabetic rats treated with SPE, 200 mg/kg/day), DM + SP-400 (diabetic rats treated with SPE, 400 mg/kg/day) and DM + Gly-3 (diabetic rats treated with glibenclamide, 3 mg/kg/day). Live body weight, fasting blood glucose (FBG) level, antidiabetic, serum biochemical and lipid profile parameters, antioxidant defense system, malondyaldehyde (MDA) and histopathological examinations in liver, kidney and pancreas were evaluated.ResultsApigenin, luteolin, quinic acid, cosmosiin and epigallocatechin were determined to be the major phenolic compounds in the SPE. Administration of the highest dose of SP extract (400 mg/kg) resulted in a significant reduction in FBG levels and glycosylated hemoglobin levels in STZ-induced diabetic rats, indicating an antihyperglycemic effect. SPE (200 and 400 mg/kg) and glibenclamide significantly improved MDA in liver and kidney tissues. In addition, SPE contributed to the struggle against STZ-induced oxidative stress by stimulating antioxidant defense systems. STZ induction negatively affected liver, kidney and pancreas tissues according to histopathological findings. Treatment with 400 mg/kg and glibenclamide attenuated these negative effects.ConclusionsIn conclusion, the extract of the aerial part of Scutellaria pinnatifida subsp. pichleri has hepatoprotective, nephroprotective and insulin secretion stimulating effects against STZ-induced diabetes and its complications due to its antidiabetic and antioxidant phytochemicals such as apigenin, luteolin, quinic acid, cosmosiin and epigallocatechin.

Hypoglycemic mechanism of Tegillarca granosa polysaccharides on type 2 diabetic mice by altering gut microbiota and regulating the PI3K-akt signaling pathway

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease threatening human health. We investigated the effects of Tegillarca granosa polysaccharide (TGP) and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin. TGP (5.1 × 103 Da) was composed of mannose, glucosamine, rhamnose, glucuronic acid, galactosamine, glucose, galactose, xylose, and fucose. It could significantly alleviate weight loss, reduce fasting blood glucose levels, reverse dyslipidemia, reduce liver damage from oxidative stress, and improve insulin sensitivity. RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance. TGP increased the abundance of Allobaculum, Akkermansia, and Bifidobacterium, restored the microbiota abundance in the intestinal tracts of mice with T2DM, and promoted short-chain fatty acid production. This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.

Effects of Cinnamon Powder on Glucose Metabolism in Diabetic Mice and the Molecular Mechanisms.

The liver is the primary organ regulating glucose metabolism. In our recent study, cinnamon improved liver function in diabetic mice. However, it is not clear whether cinnamon can reduce the glycemia of diabetic animals by regulating liver glucose metabolism. The purpose of this study was to investigate the hypoglycemic mechanism of cinnamon powder (CP) from the perspective of regulating liver glucose metabolism. To achieve this, different doses of CP (200, 400, or 800 mg/kg body weight) were given to diabetic mice by gavage once per day for 8 weeks. These mice were compared with healthy controls, untreated diabetic mice, and diabetic mice treated with metformin (the main first-line drug for type 2 diabetes). CP treatment effectively reduced fasting blood glucose levels and food intake, improved glucose tolerance and fasting serum insulin levels, and decreased glycated serum protein levels in diabetic mice. Furthermore, treatment with CP increased liver glycogen content and reduced the level of the gluconeogenesis precursor pyruvate in the liver. Data obtained by qPCR and western blotting suggested that CP improved glucose metabolism disorders by regulating AMPKα/PGC1α-mediated hepatic gluconeogenesis and PI3K/AKT-mediated hepatic glycogen synthesis. CP exhibits good hypoglycemic effects by improving hepatic glycogen synthesis and controlling hepatic gluconeogenesis. Therefore, CP may be applied as a functional food to decrease blood glucose.