Improve Insulin Resistance Research Articles

Effects of Cirsium japonicum var. maackii on avelliation of metabolic disease by improving insulin resistance

BackgroundMetabolic syndrome (MetS) refers to a group of risk factors that cause health problems, such as obesity, diabetes, dyslipidemia, and hyperglycemia. MetS is characterized by insulin resistance, which leads to abnormal insulin sensitivity. Cirsium japonicum var. maackii (CJ) is perennial herbaceous species found in Asia that exhibits antioxidant, antidiabetic, antitumor, antifungal, and anti-inflammatory activities. In this study, we aimed to measure the effects of CJ on MetS by improving insulin resistance in a db/db type 2 diabetes mouse model. After administrating CJ extract (CJE) for db/db mouse for 6 weeks, we measured with the evaluation of Insulin resistance, lipid profiles, histological analysis of liver, damage of liver and kideny.ResultsThe results showed that CJE was effective in reducing body weight and fat mas and showed a positive effect on lowering blood glucose and improving insulin sensitivity. CJE improved dyslipidemia by increasing serum-HDL levels and decreasing serum-LDL levels. In addition, CJE reduced liver and kidney damage in histological analysis.ConclusionsThese results demonstrate the anti-diabetic effects of CJE and suggest its potential for improving MetS. Therefore, CJE may have potential values as a functional food material for managing MetS.

Effect of Ficus pumila L. on Improving Insulin Secretory Capacity and Resistance in Elderly Patients Aged 80 Years Old or Older Who Develop Diabetes After COVID-19 Infection

(1) Background: It has been reported that people affected by COVID-19, an infectious disease caused by SARS-CoV-2, suffer from various diseases, after infection. One of the most serious problems is the increased risk of developing diabetes after COVID-19 infection. However, a treatment for post-COVID-19 infection diabetes has not yet been established. In this study, we investigated the effects of Ficus pumila L. extract, which has traditionally been used to reduce blood glucose levels in Okinawa, on patients who developed diabetes after COVID-19 infection. (2) Methods: In total, 128 rehabilitation patients aged 80 years old or older who developed diabetes after COVID-19 infection were included. The HOMA-β (Homeostatic model assessment of β-cell function) and HOMA-IR (Homeostatic model assessment of insulin resistance) were assessed to evaluate the glucose tolerance. (3) Results: The HOMA-β decreased and HOMA-IR increased in patients who developed after diabetes after COVID-19 infection. Subsequently, 59 patients were given Ficus pumila L. extract and their HOMA-β and HOMA-IR improved after ingestion. On the other hand, the control group of patients who did not consume Ficus pumila L. showed no improvement in both HOMA-β and HOMA-IR. (4) Conclusions: Ficus pumila L. extract, ingested by patients who developed diabetes after COVID-19 infection, stimulated insulin secretion capacity and improved insulin resistance.

Effects of exogenous insulin supplementation on lipid metabolism in peripartum obese dairy cows

Cows with high body condition scores experience more severe negative energy balance (NEB) and undergo mobilization of more body fat during the peripartum period, leading to more production of nonesterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA). Postpartum insulin secretion is lower, and insulin resistance is stronger in obese cows. Exogenous insulin supplementation has been hypothesized as a key approach for regulating NEFA in these cows. In this study, we assessed the effects of exogenous insulin supplementation on lipid metabolism, key genes regulated by insulin, and the underlying regulatory mechanism. We selected 181 periparturient multiparous obese dairy cows for the study. Cows in the insulin group (n = 96) received subcutaneous injections of 200 IU insulin (5 mL) on postpartum days 1 and 7, while cows in the control group (n = 85) received subcutaneous injections of 5 mL physiological saline on the same days. The incidence of ketosis was recorded and compared between the two groups. The results demonstrated that postpartum insulin injections significantly reduced the incidence of type II ketosis and delayed the onset time. Meanwhile, a cohort experiment was conducted on 20 cows selected from 181 field trial cows, with 10 cows in the insulin group and 10 cows in the control group. Blood samples were collected for biochemical indicators and subcutaneous adipose tissue was collected for paraffin-embedding and sectioning and RNA sequencing analysis. The results showed that insulin supplementation postpartum reduced concentrations of NEFA and BHBA as well as BCS loss, but did not affect glucose. Additionally, the expression of SREBF1 in insulin signaling pathway and the downstream-regulated lipogenesis network genes were successfully upregulated in insulin-treated healthy group. High expression of SREBF1 may be a key for postpartum insulin supplementation to improve insulin resistance, significantly reduce NEFA concentrations, and prevent or treat ketosis and fatty liver in obese cows. Postpartum administration of insulin could effectively decrease alterations of adipocytes size, which also fully validates that postpartum insulin supplementation promotes lipogenesis and reduces NEFA release.

Insulin signaling and oxidative stress: Bridging the gap between type 2 diabetes mellitus and Alzheimer's disease.

Type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) are two prevalent chronic diseases that pose significant global health challenges. Increasing evidence suggests a complex bidirectional relationship between these conditions, where T2D elevates the risk of AD, and AD exacerbates glucose metabolism abnormalities in T2D. This review explores the molecular mechanisms linking T2D and AD, focusing on the role of insulin signaling pathways and oxidative stress. A comprehensive literature search from PubMed, Web of Science, and other relevant databases was conducted and analyzed. Insulin resistance in T2D leads to impaired insulin signaling in the brain, contributing to cognitive decline and the development of AD. Hyperglycemia-induced oxidative stress exacerbates neuronal damage, promoting the formation of amyloid-β plaques and neurofibrillary tangles characteristic of AD. Clinically antidiabetic drugs such as metformin show potential against AD in preclinical studies; Many natural products such as Dendrobium nobile Lindl. have anti-T2D efficacy and are also effective against AD in various in vivo and in vitro models. Improving insulin resistance and reducing oxidative stress are important strategies in the treatment of T2D and AD. To understand the bridging role of insulin singling and oxidative stress in T2D and AD will provide insights and broader applications in alleviating T2D and AD.

Quinoa is more effective than other whole grains in the management of impaired glucose tolerance: a randomized controlled trial.

The purpose of this study was to compare the effects of quinoa versus multigrain supplementation on glycemia and lipid metabolism among individuals with impaired glucose tolerance (IGT). In total, 207 participants diagnosed with IGT were randomly assigned to the quinoa group (QG; 100 g day-1, replacing about half of the total daily staple food), multiple whole grain group (WGG; 100 g day-1), or control group (CG) and followed for one year. Biomarkers were measured before and after the intervention. At the efficacy endpoint, the quinoa group (QG) demonstrated significantly longer time in range (TIR) and normal glucose tolerance (NGT) conversion rate, along with lower rates of 2-hour postprandial glucose (2hPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), 14-day mean blood glucose (14dMBG), and diabetes mellitus development compared to those of the multigrain and control groups (P < 0.05). Significant improvements in glycated hemoglobin (HbA1c) were also found in both the quinoa and multigrain groups compared to the control group (P < 0.05). No significant difference in glycemic variability (CV) was observed between the quinoa and control groups, while a significant difference was observed between the quinoa and multigrain groups (P < 0.05). These results suggest that quinoa consumption is significantly more effective than a multiple whole-grain diet in controlling IGT by reducing postprandial glucose and HbA1c levels, improving insulin resistance, and enhancing lipid profiles, making it a superior dietary choice for managing IGT.

Berberine Improves Glucose and Lipid Metabolism in Obese Mice through the Reduction of IRE1/GSK-3β Axis-Mediated Inflammation.

Berberine (BBR) has the characteristics of repressing hyperglycemia, obesity, and inflammation, as well as improving insulin resistance. However, the underlying mechanism remains to be fully understood. This study explores whether BBR regulates inositol requiring enzyme 1 (IRE1)/glycogen synthase kinase 3 beta (GSK-3β) axis to resist obesity-associated inflammation, thereby improving glucolipid metabolism disorders. Mice were fed a high-fat diet and administrated with BBR, followed by measurement of weight change, biochemical indicators, as well as glucose and insulin tolerance. Insulin-resistant 3T3-L1 adipocyte models were established, and the model cells were treated with BBR and IRE1 inhibitors. Cell viability was detected by cell counting kit-8 assay. Inflammatory factor secretion and glucose consumption were measured via specific kits. Oil red O staining was used to observe lipid droplet formation, and protein expressions in the IRE1/GSK-3β axis were determined via Western blot. BBR reduced weight, insulin resistance, levels of triglyceride, total cholesterol, free fatty acid, high-density lipoprotein, and low-density lipoprotein but improved glucose tolerance in obese mice. BBR and IRE1 inhibitors demonstrated no cytotoxicity. BBR and IRE1 inhibitors diminished secretion of tumor necrosis factor-alpha, interleukin-6, and monocyte chemoattractant protein 1, lipid droplet formation, and values of p-IRE1/IRE1 and p-GSK-3β/GSK-3β, but elevated glucose consumption in insulin-resistant adipocytes. BBR improves glucose and lipid metabolism in obese mice through the reduction of IRE1/GSK-3β axis-mediated inflammation, showing the great potential of BBR in reversing insulin resistance in obesity.

Picrotoxane-type sesquiterpenoids from Dendrobium improve insulin resistance and increase glucose-stimulated insulin secretion.

Twelve picrotoxane-type sesquiterpenoids were isolated from Dendrobium wardianum, of which dendrowardins K-N (1-4) are new compounds and dendrowardins O and P (9, 10) are new natural products. Notably, the structure of dendrowardin K contains the rarely observed 10,11-γ-lactone ring. The structural configurations of these compounds were determined through comprehensive 1D and 2D nuclear magnetic resonance (NMR), single-crystal X-ray diffraction, and other spectroscopic analyses. Additionally, the hypoglycaemic activities of the picrotoxane-type sesquiterpenes and their analogues were systematically evaluated by determining the antidiabetic activities of these compounds and six others (13-18) obtained from genus Dendrobium. Twelve compounds (1, 2, 4-6, 8, 12, 13- 15, 17, and 18) significantly improved insulin resistance. Further experiments revealed that compound 6 improved insulin resistance by increasing GLUT-4 expression. The possible mechanism is related to AKT-related pathways, and the effects of treatment with 50μM compound 6 were comparable to those of the positive control drug metformin. Compounds 4-6 and 13-15, 17 displayed great increases in the secretion of insulin from β-TC-6 cells. On the basis of these findings, the structure-activity relationships (SARs) of picrotoxane-type sesquiterpenoids were discussed for the first time.

Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD

Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD

Application of a dynamic colonic gastrointestinal digestion model to red wines: a study of flavanol metabolism by the gut microbiota and the cardioprotective activity of microbial metabolites.

Over the last decade, research has emphasized the role of the microbiome in regulating cardiovascular physiology and disease progression. Understanding the interplay between wine polyphenols, the gut microbiota, and cardiovascular health could provide valuable insights for uncovering novel therapeutic strategies aimed at preventing and managing cardiovascular disease. In this study, two commercial red wines were subjected to in vitro dynamic gastrointestinal digestion (GIS) to monitor the flavanol-microbiota interaction by evaluating the resulting microbial metabolites. Furthermore, the cardiovascular protective activity of wine flavanol microbial metabolites was investigated, integrating their effects on antihypertensive activity, cholesterol metabolism and insulin resistance into human endothelial (EA.hy926) and hepatic (HepG2) cell lines. A significant production of microbial flavanol metabolites, with a prevalence of phenylpropionic and phenylacetic acids, valerolactones and short chain fatty acids such as butyric acid, was observed, particularly in the transverse and descending colon sections. Incubating HAECs and HepG2 cells with the colon improved cardioprotective parameters. Specifically, an increase in the vasodilator NO, an improvement in the LDL receptors and the HMGCoA enzyme, with positive effects on cholesterol metabolism, and the reduction of glycogen levels improving insulin resistance were observed.

Inhibition of Th17 cell differentiation by aerobic exercise improves vasodilatation in diabetic mice

ABSTRACT Background Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice. Methods db/db and db/m+ mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry. Results Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling. Conclusions This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.

Applications of Semaglutide for Various Diseases

Semaglutide is a gluten-like peptide 1 (GLP-1) agonist which is responsible for improving blood sugar control and losing weight. It is clinically approved by the FDA for treatment of type 2 diabetes mellitus and is designed in subcutaneous or oral dosage form. Some other diseases share common conditions with obesity and diabetes such as a high blood sugar level and insulin resistance. These factors along with some neuron issues are responsible for neurodegenerative diseases. Obesity and diabetes are two common worldwide health issues. A number of trials have been conducted to estimate the prevalence and drug effects. Scientists also study related diseases such as Non-alcoholic fatty liver disease to verify the usefulness of treatments. Semaglutide is one of the drugs being measured whether has a potential effect on these diseases. Some pre-clinical studies have indicated its therapeutic potential in non-alcoholic steatohepatitis and neurodegenerative disorders. Semaglutide has proved to be effective in treating lots of disorders, especially diabetes and obesity. However, for other diseases, it still remains uncertain even if there are some studies already tested the effectiveness. Much more detailed and considerate studies should be conducted to verify the impact. Semaglutide, the GLP-1 receptor agonist, has shown a positive impact in treating different diseases. Researchers have tested hepatoprotective and neuroprotective activity in animal and human trials to get more reliable data. It turns out that semaglutide improves insulin resistance and reduces blood sugar levels. It also protects dopaminergic neurons and reduces aggregated α-synuclein which improves Parkinson’s disease and Alzheimer’s disease conditions.

Exploring the Potential of Epigallocatechin Gallate in Combating Insulin Resistance and Diabetes.

In this study, the potential effects are evaluated of epigallocatechin gallate (EGCG) on the prognosis of diabetes and insulin resistance. In an experiment, 35 male Wistar albino rats were used and in the streptozotocin (STZ)-induced diabetic rats, the effects were examined of different doses (50 mg/kg, 100 mg/kg, 200 mg/kg) of EGCG on metabolic parameters associated with diabetes and insulin resistance. The findings show favorable effects of EGCG on fasting blood glucose levels, insulin secretion, insulin resistance, and beta cell function. In this study, it was observed that EGCG was able to significantly lower fasting blood glucose levels, especially at high doses (200 mg/kg), providing the most significant improvement. Furthermore, EGCG has been found to reduce insulin resistance and improve insulin sensitivity by increasing insulin secretion. When the biochemical parameters of increased insulin secretion are evaluated, it is also observed that it creates clinically significant changes. At doses of 100 mg/kg and 200 mg/kg, EGCG has the potential to help control diabetes by most effectively improving insulin resistance and beta cell function. The study results suggest that EGCG, especially at high doses, is an effective component in the treatment of diabetes and the management of insulin resistance. The inclusion of EGCG as a natural flavonoid in medical nutrition therapy may contribute to glycemic control and improve insulin sensitivity in individuals with diabetes. These findings suggest that EGCG may be used as an alternative option in the treatment of diabetes and future studies may further clarify the potential benefits in this area.

Sleeve Gastrectomy and Its Impact on Insulin Resistance and Metabolic Health: A Cohort Study.

Obesity is a prevalent metabolic disorder that significantly contributes to insulin resistance (IR), type 2 diabetes (T2DM), and metabolic syndrome. Sleeve gastrectomy has emerged as an effective surgical intervention for obesity, with potential benefits on metabolic health. This study investigates the impact of sleeve gastrectomy on serum insulin levels, IR (HOMA-IR), inflammatory markers, C-peptide, kidney function, and various biochemical parameters in diabetic and non-diabetic patients. A prospective cohort study was conducted, involving 199 patients over 18years old who were candidates for sleeve gastrectomy at Luqman Hakim Hospital from 2021 to 2022. Data were collected using standardized questionnaires and anthropometric measurements, and biochemical assessments were performed before surgery and 6months postoperatively. Statistical analyses included descriptive statistics, t-tests, Mann-Whitney tests, and repeated measures analysis of variances (ANOVA). The study included 199 patients (84.4% female) with a mean (± standard deviation (SD)) age of 39.79 ± 11.30years. Significant reductions were observed in weight, BMI, and abdominal circumference across all patient groups. Diabetic patients showed marked improvements in fasting blood sugar, 2-h postprandial blood sugar, and glycosylated hemoglobin levels. Insulin resistance decreased significantly, as did serum insulin and C-peptide levels. Improvements in lipid profiles and inflammatory markers were also noted. Insulin use post-surgery showed a significant inverse relationship with glycemic control improvement. Sleeve gastrectomy is a safe and effective procedure for obese patients, significantly improving insulin resistance and various obesity-associated diseases within 6months post-surgery.

Association Between Clinical Use of Lansoprazole and the Risk of Coronary Heart Disease: A Nationwide Pharmacoepidemiological Cohort Study.

Proton pump inhibitors (PPIs) are widely prescribed for gastrointestinal disorders. Lansoprazole, a PPI, has been recognized for its potential effects of improving insulin resistance, reduction of oxidative stress, and improvement in atherosclerosis through peroxisome proliferator-activated receptor gamma (PPARγ) induction. This study aims to investigate whether lansoprazole poses a distinct risk of coronary heart disease (CHD) compared to other PPIs. A retrospective cohort study utilized data from the National Health Insurance Research Database in Taiwan spanning from 2000 to 2013. The exposed cohort included 1666 patients with lansoprazole use, while the comparison cohort comprised 6664 patients using other PPIs. The primary outcome was incident CHD. Cox regression models were employed to assess the association between lansoprazole use and CHD risk, presenting hazard ratios (HRs) and 95% confidence intervals (CIs). Patients prescribed lansoprazole demonstrated a significantly reduced risk of CHD compared to those undergoing other PPI treatments in individuals without a history of CHD. Lansoprazole users exhibited a 25% lower risk of developing CHD compared to other PPI users (adjusted HR 0.75; 95% CI 0.65-0.87). Intriguingly, this inverse association between lansoprazole use and CHD risk was consistent across genders and various age groups. This study suggests that lansoprazole is associated with a decreased risk of CHD in comparison to other PPIs in patients without a history of CHD. Further research is warranted to elucidate the clinical implications of these findings.

Neuroprotective effects of GLP-1 class drugs in Parkinson’s disease

Parkinson’s disease (PD) is a chronic, progressive neurological disorder primarily affecting motor control, clinically characterized by resting tremor, bradykinesia, rigidity, and other symptoms that significantly diminish the quality of life. Currently, available treatments only alleviate symptoms without halting or delaying disease progression. There is a significant association between PD and type 2 diabetes mellitus (T2DM), possibly due to shared pathological mechanisms such as insulin resistance, chronic inflammation, and mitochondrial dysfunction. PD is caused by a deficiency of dopamine, a neurotransmitter in the brain that plays a critical role in the control of movement. Glucose metabolism and energy metabolism disorders also play an important role in the pathogenesis of PD. This review investigates the neuroprotective mechanisms of glucagon-like peptide-1 (GLP-1) and its receptor agonists, offering novel insights into potential therapeutic strategies for PD. GLP-1 class drugs, primarily used in diabetes management, show promise in addressing PD’s underlying pathophysiological mechanisms, including energy metabolism and neuroprotection. These drugs can cross the blood–brain barrier, improve insulin resistance, stabilize mitochondrial function, and enhance neuronal survival and function. Additionally, they exhibit significant anti-inflammatory and antioxidative stress effects, which are crucial in neurodegenerative diseases like PD. Research indicates that GLP-1 receptor agonists could improve both motor and cognitive symptoms in PD patients, marking a potential breakthrough in PD treatment and prevention. Further exploration of GLP-1’s molecular mechanisms in PD could provide new preventive and therapeutic approaches, especially for PD patients with concurrent T2DM. By targeting both metabolic and neurodegenerative pathways, GLP-1 receptor agonists represent a multifaceted approach to PD treatment, offering hope for better disease management and improved patient outcomes.

The Application of Nanomaterials in the Treatment of Pancreatic-Related Diseases.

Pancreatic diseases, typically including pancreatic cancer, pancreatitis, and diabetes, pose enormous threats to people's lives and health. To date, therapeutics with high therapeutic efficacy and low side effects are still challenging. With the development of nanotechnology, nanomaterials have successfully been applied in pancretic disease treatment. Here, we first introduce the diversity of nanomaterials and the effects of their different physicochemical properties on pancreatic function. Following this, we analyze the potential of nanomaterials to enhance pancreatic targeting by overcoming the challenges of traditional delivery methods through surface modifications, structural adjustments, and optimized drug loading. Then, we introduce the application of structurally optimized nanomaterials to pancreatic-related diseases. For instance, on pancreatic cancer (as drug delivery platforms, for the promotion of radiation therapy, and as multifunctional tools), pancreatitis (as drug delivery systems, anti-inflammatory and anti-fibrotic agents), and diabetes (as insulin delivery carriers, for protecting pancreatic β cells, and for improving insulin resistance). Through analysis of the progress of current research, we summarize how nanomaterials can enhance treatment efficacy while minimizing side effects. Finally, we look forward to the prospects of nanomaterials in pancreatic disease treatment.

Evaluation of Hypoglycemic Polyphenolic Compounds in Blueberry Extract: Functional Effects and Mechanisms.

Blueberries are rich in polyphenols, which exhibit significant anti-diabetic activity. In this study, polyphenolic compounds with potential hypoglycemic activity were identified from blueberry polyphenol extract (BPE). This research focused on assessing the hypoglycemic effects of BPE and its polyphenolic compounds (dihydroquercetin and gallic acid) on diabetic mice induced by streptozotocin (STZ) and high-fat diet (HFD), as well as the related fundamental mechanisms. The findings revealed that BPE treatment effectively reduced levels of fasting blood glucose (FBG) by decreasing hepatic oxidative stress, regulating lipid metabolism disorders and improving insulin resistance. Investigations into the insulin signaling pathway revealed that BPE can modulate the expression of Egfr, Insr, Irs-1, Pi3k and Akt, thereby influencing glucose metabolism. This study provides a research foundation for considering blueberry polyphenols as a nutritional dietary supplement for the prevention and intervention of diabetes.

Rice Kefiran Ameliorates Obesity and Hepatic Steatosis Through the Change in Gut Microbiota

Obesity is a global epidemic and a significant risk factor for various diseases. Obesity and dysbiosis are associated, drawing attention to the mechanisms that regulate the gut microbiota. In this study, we focused on the postbiotic effects of rice kefiran (Kef), a functional product of Lactobacillus kefiranofaciens cultured in a rice-based medium, on obesity and its complications. Although Kef has the potential to improve obesity, the underlying mechanisms remain unknown. Therefore, we aimed to elucidate the mechanisms underlying changes in gut microbiota. The administration of Kef significantly suppressed diet-induced body weight gain, reduced liver fat accumulation, and modestly improved insulin resistance. Among the gut bacteria, Lachnospiraceae and Lachnoclostridium, which were positively correlated with obesity, decreased in mice administered Kef. In contrast, Bacteroides and Alistipes, both reported to ameliorate obesity, were increased. Consistent with the changes in the gut microbiota, Kef increased fecal acetate levels, which ameliorated obesity and hepatic steatosis. Predictive metagenomic analysis suggested that Kef administration increased the abundance of KEGG orthologs, associated with carbohydrate metabolism and improvements in insulin resistance. In conclusion, Kef improves diet-induced obesity, hepatic steatosis, and insulin resistance by regulating the gut microbiota’s composition.

Hovenia dulcis (Guaizao) polysaccharide ameliorates hyperglycemia through multiple signaling pathways in rats with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) poses a significant threat to human health, with its incidence and mortality rates increasing annually. This study investigated the hypoglycemic effects and underlying mechanisms of pure Hovenia dulcis (Guaizao) polysaccharide (HDPs-2A) in rats subjected to a high-fat and high-sugar diet combined with streptozotocin-induced T2DM. Oral administration of HDPs-2A resulted in significant increases in body weight and liver glycogen levels compared to untreated controls. Moreover, a reduction in fasting blood glucose levels, alleviation of hyperinsulinemia, enhanced glucose tolerance, and improved insulin resistance were observed in the HDPs-2A-treated group. HDPs-2A also effectively reversed diabetes-induced dyslipidemia, as evidenced by decreased total cholesterol and triglyceride levels, alongside increased high-density lipoprotein cholesterol levels. Histopathological analyses confirmed that HDPs-2A partially repaired liver tissue damage by mitigating oxidative stress responses in the liver. Additionally, treatment with HDPs-2A significantly elevated short-chain fatty acid levels in T2DM rats. Real-time quantitative PCR and Western blot analyses indicated that HDPs-2A significantly enhanced the expression of InsR, IRS2, PI3K, Akt, and GLUT4, suggesting that HDPs-2A regulates insulin resistance and glycometabolism through the activation of the PI3K/Akt signaling pathway. Furthermore, HDPs-2A appeared to modulate the expression of GS, GSK-3β, and FoxO1 to improve glucose metabolism and reduce insulin resistance. It also improved glucose metabolism by activating the AMPK pathway and modulating G6Pase and PEPCK expression. This study provides novel insights into the antidiabetic effects of HDPs, positioning them as promising nutritional agents for the management of T2DM.

Anti-Diabetic Effects of &lt;i&gt;Cordyceps Militaris&lt;/i&gt; Extract on Weight, Blood Glucose, and Insulin Resistance in Diabetic Model Mice

Objectives: This study investigates the anti-diabetic effects of &lt;i&gt;Cordyceps militaris&lt;/i&gt; extract on diabetic model mice (db/db mouse).Methods: Diabetic mice (db/db) were compared to normal control group (NC). The positive control group received Metformin (Met), while other groups received &lt;i&gt;Cordyceps militaris&lt;/i&gt; extract, including &lt;i&gt;ARA301_L&lt;/i&gt;. Body weight, fasting blood glucose levels (FBGL), oral glucose tolerance tests (OGTT), insulin tolerance tests (ITT), blood lipid profiles, and tissue analysis were conducted.Results: Diabetic mice showed significantly higher body weight compared to normal mice. The positive control group maintained stable weight over 56 days, while the &lt;i&gt;Cordyceps militaris&lt;/i&gt; extract groups showed slight weight decreases, with a marked reduction in the &lt;i&gt;ARA301_L&lt;/i&gt; group. FBGLs were significantly lower in treated groups than in control groups. OGTT indicated better glucose regulation in treated groups, though differences among them were not significant. ITT showed lower blood glucose levels in treated groups, indicating improved insulin resistance. Blood lipid profiles revealed significant reductions in total cholesterol (TC) and AST in the &lt;i&gt;ARA301_L&lt;/i&gt; group. Liver tissue analysis showed decreased expression of lipid metabolism and inflammation-related genes, particularly PPAR&lt;i&gt;γ&lt;/i&gt; and SREBP-1c. Muscle and adipose tissues displayed increased GLUT4 protein and reduced inflammatory gene expression.Conclusions: &lt;i&gt;Cordyceps militaris&lt;/i&gt; extract has more positive effects than metformin on body weight, insulin resistance, sugar metabolism, fatty liver, and inflammation in diabetic mice. It also has a similar positive effect as metformin on blood lipid concentration and liver damage. This suggests the potential of diabetes management in &lt;i&gt;Cordyceps militaris&lt;/i&gt; extract.