Increased Insulin Sensitivity Research Articles

Deletion of Arntl, a component of the molecular clock, in adipocytes leads to cellular hypertrophy by increasing insulin sensitivity via FGF21

Brain and muscle Arnt-like protein 1 (BMAL1), encoded by Aryl hydrocarbon receptor nuclear translocator like 1 (Arntl) gene, is a transcription factor that regulates the circadian rhythm of the expressions of several genes. The link between the loss of BMAL1 function in adipose tissue and obesity has been reported. Although these previous studies have suggested that dysregulation of lipolysis is a contributing factor, but the detailed mechanism has not been fully understood. This study aimed to elucidate the role of BMAL1 in adipocytes using adipocyte-specific Arntl deficient (AAKO) mice. Deletion of Arntl in adipocytes leads to increased cellular insulin sensitivity, which in turn, inhibited lipolysis in adipocytes and caused cellular hypertrophy. The expression levels of Fgf21 in adipose tissue were significantly elevated in AAKO mice compared to Arntlflox/flox mice. Double knockout of Arntl and Fgf21 in adipocytes abolished metabolic phenotypes such as decreased circulating non-esterified fatty acid levels, adipocyte hypertrophy, and increased insulin sensitivity in AAKO mice. These results indicated that BMAL1 regulates fat mobilization and insulin signaling in adipocytes via FGF21 during the stationary phase. This is the possible mechanism by which disruption of circadian rhythm induces obesity.

Mango Consumption Is Associated with Increased Insulin Sensitivity in Participants with Overweight/Obesity and Chronic Low-Grade Inflammation

Background/Objectives: Chronic low-grade inflammation is associated with insulin resistance and poor glycemic control, leading to the development of type 2 diabetes mellitus (T2DM). The present study investigated the effect of regular mango intake on inflammation and insulin sensitivity in participants with overweight or obesity and chronic low-grade inflammation. Methods: A human clinical study was performed using a randomized, controlled, two-arm, parallel design with a 2 h oral glucose tolerance test (OGTT) administered before and after 4 weeks (4 W) of mango or control product intake (1 cup/twice a day). Fasting and time course blood sampling for 2 h post-OGTT were analyzed for effects on plasma metabolic and inflammation endpoints using analysis of covariance and repeated-measure approaches (SAS 9.4). Results: Forty-eight adults (37.6 ± 2.8 years, 30.5 ± 4.1 BMI kg/m2) completed the study. Markers of inflammation (IL-6, TNFα, hs-CRP) were not different at the end of 4 W (p > 0.05). The intervention did not significantly influence fasting glucose concentrations; however, insulin was significantly lowered with the mango compared to the control intervention (8.2 ± 1.2 vs. 15.3 ± 1.2 µIU/mL respectively, p = 0.05). Furthermore, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), along with the disposition index (DI), was significantly improved in the mango compared to the control interventions (HOMA-IR, 2.28 ± 1.19 vs. 4.67 ± 1.21, p = 0.03; DI, 2.76 ± 1.02 vs. 5.37 ± 1.03, p = 0.04). Mean insulin concentrations were also significantly lower at W4 compared to W0 after the OGTT in the mango vs. control intervention (intervention × week effect, p = 0.04). Relative expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), a gene regulating endogenous antioxidant defense, was non-significantly increased twofold in the mango intervention (W4 vs. W0). Conclusions: Collectively, the data suggest that mango intake increased insulin sensitivity in individuals with chronic low-grade inflammation, possibly through activating Nrf-2 genes and increasing cellular antioxidant status. The data warrant further research on consuming mango fruit as part of a dietary pattern to address insulin resistance and the mechanisms underpinning the actions of mango intake.

Liver-innervating vagal sensory neurons are indispensable for the development of hepatic steatosis and anxiety-like behavior in diet-induced obese mice

The visceral organ-brain axis, mediated by vagal sensory neurons, is essential for maintaining various physiological functions. Here, we investigate the impact of liver-projecting vagal sensory neurons on energy balance, hepatic steatosis, and anxiety-like behavior in mice under obesogenic conditions. A small subset of vagal sensory neurons innervate the liver and project centrally to the nucleus of the tractus solitarius, area postrema, and dorsal motor nucleus of the vagus, and peripherally to the periportal areas in the liver. The loss of these neurons prevents diet-induced obesity, and these outcomes are associated with increased energy expenditure. Although males and females exhibit improved glucose homeostasis following disruption of liver-projecting vagal sensory neurons, only male mice display increased insulin sensitivity. Furthermore, the loss of liver-projecting vagal sensory neurons limits the progression of hepatic steatosis. Intriguingly, mice lacking liver-innervating vagal sensory neurons also exhibit less anxiety-like behavior compared to control mice. Modulation of the liver-brain axis may aid in designing effective treatments for both psychiatric and metabolic disorders associated with obesity and MAFLD.

Diosmin as Antidiabetic Agent: A Comprehensive Mechanistic Approach

Diabetes mellitus is a chronic metabolic disorder which occurs due to deficiency of insulin or resistance to insulin receptor. There are naturally occurring compounds found in various plants, foods, and herbs that have potent anti-diabetic properties. They help to control blood sugar levels by increasing insulin sensitivity and stimulating glucose absorption in cells. Diosmin, a flavonoid glycoside found primarily in citrus fruits, has shown outstanding potential as a therapeutic agent due to its significant anti-diabetic, anti-inflammatory, antioxidant, and vascularprotective properties. Here, we review the diosmin molecular mechanism and its ability to regulate oxidative stress, reduce inflammatory cytokines, improve endothelial function, and explore its pathway for anti-diabetic properties. In addition, preclinical and clinical data that supports diosmin efficacy in decreasing blood glucose, enhancing insulin sensitivity, and delaying the development of diabetic squeal was considered. Furthermore, diosmin has shown great potential in a variety of therapeutic domains when associated with other drugs in combinational studies, and many diosmin-based drug delivery studies have been reported. This review also investigates the molecular processes and clinical uses of diosmin, emphasizing its therapeutic potential as an additional drug in diabetes control through a comprehensive review of current studies.

Effect of Prebiotic Supplementation on Health Status in Adults with Prediabetes: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Prediabetes with a considerable progression rate is a primary risk factor for type 2 diabetes if left untreated. Dietary interventions examining the health effects of prebiotic consumption on health status have been studied in subjects with prediabetes, but the results are controversial. This study aimed to investigate whether prebiotic consumption can favorably alter metabolic status as well as anthropometric features in subjects with prediabetes. Electronic databases were searched up to January 2024, and randomized clinical trials examining the effect of prebiotic consumption on glycemic status, lipid profile, and/or anthropometric features in adults with prediabetes were selected. Data from 10 selected studies were extracted. In total, 546 subjects were included in our analysis, of whom 258 were allocated to prebiotic supplemented group and 288 to control group. Our results demonstrated a significant reduction in body fat (BF) percentage (standardized mean difference: -1.27 %, 95% confidence interval: -2.33, -0.22) after prebiotic supplementation. We found no significant alterations in metabolic indices, including fasting plasma glucose, insulin, glycosylated hemoglobin A1c, homeostasis model assessment of insulin resistance, total cholesterol, triglyceride, and low- and high-density lipoprotein cholesterol concentrations. In addition, we did not notice a significant effect of prebiotic consumption on other anthropometrics, including body mass index and waist circumference. There was no fair evidence that prebiotic consumption could improve metabolic and anthropometric features in subjects with prediabetes. Yet, a significant reduction in BF might support the beneficial effect of prebiotics when aiming at preventing diabetes through lifestyle modifications and weight management. In addition, the reduction in BF can be of clinical significance, indicating the potential of prebiotics to increase insulin sensitivity, which can positively affect people with prediabetes. Nevertheless, current findings should be taken with caution due to the very low certainty in the pooled estimate for the majority of outcomes. Future studies are needed to investigate the effect of prebiotics on health status in people with prediabetes. This trial was registered at PROSPERO as CRD42023473082.

The Role of Quercetin and Exercise in Modulating Apoptosis and Cardiomyopathy via PI3K/AKT/FOXO3 Pathways in Diabetic Obese Rats.

Quercetin and exercise both have antidiabetic effects through decreasing blood glucose while increasing insulin sensitivity. Therefore, the present study aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) exercises along with quercetin administration on apoptosis and cardiomyopathy in diabetic obese rats. In this experimental study, 35 male Wistar rats [diabetic rats for experimental groups and normal rats for healthy control (HC)] were divided into seven groups (for each group n=5): HC, diabetic control (DC), diabetic quercetin control (DQC), diabetic HIIT (DHT), diabetic MICT (DMT), DHT with quercetin (DQHT) and DMT with quercetin (DQMT). The rats were fed a high-fat diet (HFD) for 8 weeks and a low dose of streptozotocin (STZ) was administered to create a model of type 2 diabetes mellitus (T2DM). Eight weeks of HIIT and MICT with or without quercetin treatment were performed. Quercetin was used at 15 mg/kg, as a suspension in carboxymethyl cellulose (CMC) at a concentration of 0.5%. One-way analysis of variance with LSD's post-hoc test with a significant level of P≤0.05 was used to analyze data. Just 8 weeks of HIIT and MICT protected the protein content of PI3K, AKT, and FOXO3 and caspase-8 (Casp- 8) gene expression in heart tissues (P<0.05). Quercetin and both training protocols decreased blood glucose, while improving inflammatory markers and the lipid profile (P<0.05). Reduction in blood glucose along with improvements in the inflammatory markers and the lipid profile by quercetin injection may be a promising approach for the development of new antidiabetic medications. In addition, both training protocols showed potentially successful diabetic cardiomyopathy treatments through modulating the FOXO3 and PI3K/AKT pathways.

Shilajit Mitigates Diabetes‐Induced Testicular Dysfunction in Mice: A Modulation in Insulin Sensitivity, Germ Cell‐Junctional Dynamics, and Oxido‐Apoptotic Status

Diabetes is a chronic metabolic condition that causes testicular damage by high oxidative stress, rendering 35% of afflicted people infertile. Shilajit is a traditional Indian medicine known for its antioxidant, antidiabetic, and aphrodisiac properties. However, its effectiveness on diabetes‐induced testicular dysfunction remains unclear. Therefore, the current investigation aimed to determine whether Shilajit could restore testicular functions in diabetic mice. Two days postpartum male Parkes mice received a single intraperitoneal injection of streptozotocin (STZ) (90 mg/kg BW) to induce diabetes. Three months postinjection, the effects of daily Shilajit (100 and 200 mg/kg BW) treatment were evaluated for one spermatogenic cycle in adult diabetic mice, using Empagliflozin (10 mg/kg BW) as a positive control. In STZ‐induced diabetic mice, testicular functions were compromised due to disruptions in testosterone biosynthesis, changes in germ‐cell ratios, and increased oxidative stress and apoptosis. Shilajit restored glycemic status in diabetic mice by significantly decreasing serum glucose, insulin level, and homeostasis model assessment of insulin resistance (HOMA‐IR) value while increasing insulin sensitivity. These effects were comparable to those observed with conventional antidiabetic medication Empagliflozin. Further, Shilajit stimulates steroidogenesis and germ cell dynamics of diabetic mice by increasing the activity of StAR, 3β‐HSD, and 17β‐HSD enzymes and 1C:2C, 4C:S‐Ph, and 1C:4C germ cell ratios, respectively. Shilajit also improves blood–testis barrier (BTB) functioning by increasing expression of ZO‐1, Connexin‐43, N‐Cadherin, and β‐catenin as well as oxidative status and apoptosis by modulating NF‐E2–related factor 2 (Nrf‐2)/heme oxygenase 1 (HO‐1) signaling and Bax/Bcl‐2 ratio. Subsequently, Shilajit improved the histoarchitecture of testis and epididymis in diabetic mice and recovered both qualitative and quantitative sperm parameters, as seen by higher percentages of sperm motility, viability, and normal sperm morphology as well as increased sperm numbers in cauda epididymis. In summary, Shilajit restores glycemic status, increases insulin sensitivity, stimulates steroidogenesis, and improves testicular functions through Sertoli cell and Nrf‐2/HO‐1 signaling in STZ‐induced diabetic mice.

Activation of SIRT1 by SRT1720 alleviates dyslipidemia, improves insulin sensitivity and exhibits liver-protective effects in diabetic rats on a high-fat diet: New insights into the SIRT1/Nrf2/NFκB signaling pathway.

Insulin resistance and diabetes are associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) conditions, which are distinguished by metabolic dysfunction, oxidative stress and inflammation. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, is fundamental in regulating metabolic pathways, reducing inflammation, and improving antioxidant defenses. This is the first study to investigate the effects of SRT1720, a SIRT1 activator, in diabetic rats on a high-fat diet. SRT1720 significantly lowered fasting blood glucose and insulin levels and enhanced glucose tolerance and HOMA-IR and QUICKI scores, indicating increased insulin sensitivity. The treatment also reduced total cholesterol, triglycerides, and LDL levels, showing amelioration of dyslipidemia. Moreover, SRT1720 lowered markers of liver fibrosis, including TGF-β, TIMP-1, Col1a1, and hydroxyproline, and decreased inflammation by reducing NFκB activity and pro-inflammatory cytokines (TNF-α and IL-6). Furthermore, SRT1720 augmented Nrf2 activity and HO-1 levels. Consequently, the SRT1720's protective role improved liver function and histology and prolonged rats' survival. These functions were suppressed by the co-administration of the SIRT1 inhibitor EX527, confirming that the beneficial effects of SRT1720 are SIRT1-dependent. Correlation analyses uncovered that increased SIRT1 activity was strongly associated with decreased oxidative stress, inflammation, insulin resistance, and fibrosis markers. To conclude, our results find that SRT1720 represents a promising therapeutic strategy for managing Type 2 diabetes in NAFLD or NASH patients possibly through the modulation of the SIRT1/Nrf2/NFκB signaling pathwa. SRT1720 could potentially halt or reverse the progression of these conditions and associated complications and merits further investigations.

A perspective on intermittent fasting and cardiovascular risk in the era of obesity pharmacotherapy.

Intermittent fasting has been linked to metabolic health by improving lipid profiles, reducing body weight, and increasing insulin sensitivity. However, several randomized clinical trials have shown that intermittent fasting is not more effective than standard daily caloric restriction for short-term weight loss or cardiometabolic improvements in patients with obesity. Observational studies also suggest cardiovascular benefits from extended rather than reduced eating windows, and indicate that long-term intermittent fasting regimens may increase the risk of cardiovascular disease mortality. In this perspective, we discuss evidence that may support potential adverse effects of intermittent fasting on cardiovascular health through the loss of lean mass, circadian misalignment and poor dietary choices associated with reward-based eating. Given the ongoing revolution in obesity pharmacotherapy, we argue that future research should integrate anti-obesity medications with dietary strategies that confer robust benefits to cardiometabolic health, combine exercise regimens, and consider genetic factors to personalize obesity treatment. Comprehensive approaches combining diet, pharmacotherapy, and lifestyle modifications will become crucial for managing obesity and minimizing long-term cardiovascular risk.

In-Silico Study of Compounds in The Clove Plant (Syzygium aromaticum L.) As Anti-Diabetic Candidate Targeted at The PPARγ Receptor

Diabetes mellitus is a disease caused by multiple etiologies characterized by high blood sugar levels and accompanied by dysfunction in carbohydrate, lipid, and protein metabolism due to insulin insufficiency. Peroxisome proliferator-activated receptor-γ (PPARγ) is nuclear receptor that plays a role in lowering blood sugar levels by increasing insulin sensitivity through carbohydrate and lipid metabolism, also regulating glucose homeostasis. Clove (Syzygium aromaticum L.) has the potential to reduce blood sugar level based on in vivo tests, but the molecular mechanism is still unknown. This study aims to evaluate the bioactive compounds in clove that have potential as antidiabetic drugs using in silico studies through several analyses: Lipinski's rule of five and ADMET prediction, followed by pharmacophore screening and molecular docking against PPARγ. Our results from ten bioactive compounds found in clove (eugenol, gallic acid, quercetin, kaempferol, β-caryophyllene, eugenitin, myricetin, crategolic acid, stigmasterol, and oleanolic acid), kaempferol exhibited the best potential as a PPARγ receptor agonist, with binding affinity and inhibition constant values of -4.68 kcal/mol and 369.30 μM. Still, it is needed to confirm those activities through a series of in vitro tests to prove the potential of cloves as an antidiabetic candidate targeting PPARγ

Red Wine: Poison or the Secret to Eternal Youth?

Red wine has been the subject of extensive research due to its complex polyphenolic composition and potential health effects on the human body. This review examines the cardioprotective effects of red wine, highlighting the role of polyphenols in promoting cardiovascular health, increasing insulin sensitivity, and offering protective benefits against type 2 diabetes and neurodegenerative diseases. Despite these potential benefits, red wine consumption is also associated with several adverse effects, including liver damage, headaches, and increased risk of depression. This duality highlights the importance of moderation in alcohol consumption..

Therapeutic Potential of Cinnamon Oil: Chemical Composition, Pharmacological Actions, and Applications.

Cinnamon oil, an essential oil extracted from plants of the genus Cinnamomum, has been highly valued in ancient Chinese texts for its medicinal properties. This review summarizes the chemical composition, pharmacological actions, and various applications of cinnamon oil, highlighting its potential in medical and industrial fields. By systematically searching and evaluating studies from major scientific databases including Web of Science, PubMed, and ScienceDirect, we provide a comprehensive analysis of the therapeutic potential of cinnamon oil. Research indicates that cinnamon oil possesses a wide range of pharmacological activities, covering antibacterial, anti-inflammatory, anti-tumor, and hypoglycemic effects. It is currently an active ingredient in over 500 patented medicines. Cinnamon oil has demonstrated significant inhibitory effects against various pathogens comprising Staphylococcus aureus, Salmonella, and Escherichia coli. Its mechanisms of action include disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, suggesting its potential as a natural antimicrobial agent. Its anti-inflammatory properties are evidenced by its ability to suppress inflammatory markers like vascular cell adhesion molecules and macrophage colony-stimulating factors. Moreover, cinnamon oil has shown positive effects in lowering blood pressure and improving metabolism in diabetic patients by enhancing glucose uptake and increasing insulin sensitivity. The main active components of cinnamon oil include cinnamaldehyde, cinnamic acid, and eugenol, which play key roles in its pharmacological effects. Recently, the applications of cinnamon oil in industrial fields, including food preservation, cosmetics, and fragrances, have also become increasingly widespread. Despite the extensive research supporting its medicinal value, more clinical trials are needed to determine the optimal dosage, administration routes, and possible side effects of cinnamon oil. Additionally, exploring the interactions between cinnamon oil and other drugs, as well as its safety in different populations, is crucial. Considering the current increase in antibiotic resistance and the demand for sustainable and effective medical treatments, this review emphasizes the necessity for further research into the mechanisms and safety of cinnamon oil to confirm its feasibility as a basis for new drug development. In summary, as a versatile natural product, cinnamon oil holds broad application prospects and is expected to play a greater role in future medical research and clinical practice.

Efficacy of red algae and artichoke extracts in disrupting antioxidant/PI3K/RBP-4 pathway in high-fat diet-induced metabolic disorders in rats

BackgroundInsulin resistance (IR) leads to various metabolic abnormalities, including diabetes mellitus, obesity, nonalcoholic steatohepatitis, and neurodegenerative disorders. Natural products rich in nontoxic phytochemicals are cost-effective and widely used to manage insulin resistance, reducing drug interactions. Artichoke stems and red algae contain several phytochemical compounds that exert antioxidant and anti-inflammatory effects.AimThis study aims to explore and compare the preventive and therapeutic effects of red algae and artichoke stem extracts against high-fat diet-induced insulin resistance and then compare their impacts with those of the reference drug metformin, which is commonly used for treating type 2 diabetes.MethodsThe animals were fed a high-fat diet for eight weeks to induce insulin resistance. The plants were then treated orally with 100 mg/kg body weight red algae, artichoke extracts, or metformin per day for 14 days. The protective rat groups received the extracts at the same dose for 14 days before being fed the high-fat diet for eight weeks. Commercial kits and standardized methods were used to measure blood diabetic profiles (glucose, insulin, lipid profile, fructosamine, and retinol-binding protein-4 (RBP-4)) and liver oxidative stress parameters, nuclear factor-κβ (NF-κβ), peroxisome proliferator-activated receptor gamma (PPAR-γ), phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), retinol-binding protein-4 (RBP-4), and phosphatase and tensin homolog (PTEN).ResultsOur results showed that both extracts inhibited NF-κB and PTEN while enhancing PI3K, RPB-4, and PPAR-γ due to their potent antioxidant properties. They also increased insulin sensitivity, as reflected by reduced blood glucose and lipid profile levels and normalized fructosamine and RBP-4. Additionally, these extracts prevent oxidative stress-induced hepatic and nephric cell dysfunction, as confirmed by improved blood, liver, and kidney parameters.ConclusionTherefore, both extracts could be good antioxidant treatments for oxidative stress-related insulin resistance because they restore the balance of the PI3K/PPAR-γ/RBP-4 pathway. This pathway increases glucose uptake, stops gluconeogenesis, speeds up lipid metabolism, and stops the inflammation pathway.

Biomarkers and Seaweed-Based Nutritional Interventions in Metabolic Syndrome: A Comprehensive Review.

Metabolic Syndrome (MetS) is a complex, multifactorial condition characterized by risk factors such as abdominal obesity, insulin resistance, dyslipidemia and hypertension, which significantly contribute to the development of cardiovascular disease (CVD), the leading cause of death worldwide. Early identification and effective monitoring of MetS is crucial for preventing serious cardiovascular complications. This article provides a comprehensive overview of various biomarkers associated with MetS, including lipid profile markers (triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio), inflammatory markers (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), leptin/adiponectin ratio, omentin and fetuin-A/adiponectin ratio), oxidative stress markers (lipid peroxides, protein and nucleic acid oxidation, gamma-glutamyl transferase (GGT), uric acid) and microRNAs (miRNAs) such as miR-15a-5p, miR5-17-5p and miR-24-3p. Additionally, this review highlights the importance of biomarkers in MetS and the need for advancements in their identification and use for improving prevention and treatment. Seaweed therapy is also discussed as a significant intervention for MetS due to its rich content of fiber, antioxidants, minerals and bioactive compounds, which help improve cardiovascular health, reduce inflammation, increase insulin sensitivity and promote weight loss, making it a promising nutritional strategy for managing metabolic and cardiovascular health.

Liver-innervating vagal sensory neurons are indispensable for the development of hepatic steatosis and anxiety-like behavior in diet-induced obese mice.

The visceral organ-brain axis, mediated by vagal sensory neurons, is essential for maintaining various physiological functions. Here, we investigate the impact of liver-projecting vagal sensory neurons on energy balance, hepatic steatosis, and anxiety-like behavior in mice under obesogenic conditions. A small subset of vagal sensory neurons in both the left and right ganglia innervate the liver and project centrally to the nucleus of the tractus solitarius, area postrema, and dorsal motor nucleus of the vagus, and peripherally to the periportal areas in the liver. Surprisingly, the loss of liver-projecting vagal sensory neurons via caspase-induced selective destruction of advillin-positive neurons prevents diet-induced obesity, and these outcomes are associated with increased energy expenditure. Although males and females exhibit improved glucose homeostasis following disruption of liver-projecting vagal sensory neurons, only male mice display increased insulin sensitivity. Furthermore, the loss of liver-projecting vagal sensory neurons limits the progression of hepatic steatosis in mice fed a steatogenic diet. Intriguingly, mice lacking liver-innervating vagal sensory neurons also exhibit less anxiety-like behavior compared to control mice. Therefore, modulation of the liver-brain axis may aid in designing effective treatments for both psychiatric and metabolic disorders associated with obesity and MAFLD.

The Therapeutic Role of Gastrodin in Combating Insulin Resistance, Inflammation, and Oxidative Stress Induced by Bisphenol-A

Objective Insulin resistance is a key feature of, type 2 diabetes mellitus (T2DM), and it has been linked to an environmental pollutant bisphenol-A (BPA). Gastrodin, a derivative of Chinese medicinal herb, has antioxidant and anti-inflammatory properties that can potentially ameliorate BPA-induced insulin resistance in albino rats. Method The study involved five groups of six rats each, including normal control, BPA-treated, metformin-treated, and gastrodin plus BPA-treated groups Insulin sensitivity index, homeostasis model assessment- index of insulin resistance (HOMA IR), and fasting insulin levels were assessed. Using ELISA, the study measured protein levels, including High-Sensitivity C-reactive Protein (hs-CRP,) Glucose Transporter 1 (GLUT1), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), AMP-Activated Protein Kinase (AMPK), Inducible Nitric Oxide Synthase (iNOS), caspase-3, and Nuclear factor erythroid 2–related factor 2 (Nrf2), and analyzed factors like thiobarbituric acid reactive substances-malondialdehyde (TBARS-MDA), reduced glutathione, and catalase activity. Results BPA administration causes insulin resistance in albino rats, reducing insulin sensitivity. Gastrodin treatment attenuates resistance, improves glucose levels, and increased insulin sensitivity. Gastrodin also mitigates oxidative stress.by reducing reactive oxygen species (ROS) production and restoring antioxidant enzyme activities, while TBARS-MDA was reduced. Studied inflammatory indicators included; C-reactive protein, Tumor necrosis factor (TNF-α), and Interleukin 6. Notably, the administration of bisphenol-A caused a 2–3 fold increase in the serum levels of hs-CRP, TNF-α, and IL-6. All treatments by gastrodin (high and low doses) decreased these observed effects by bisphenol-A to values similar to the standard (metformin) and normal control rats. Gastrodin exerted its protective benefits via activating the AMPK/Nrf2 signaling pathway, increasing AMPK phosphorylation and Nrf2 nuclear translocation, resulting in improved cellular defense against oxidative stress. Indicators of possible inflammations on bisphenol-A treatment were also investigated. Conclusion This shows that gastrodin might be a promising therapeutic drug for the prevention and treatment of insulin resistance-related problems.

The Significance of Plant Nutrition in the Creation of the Intestinal Microbiota-Prevention of Chronic Diseases: A Narrative Review.

Dysbiosis of the gastrointestinal tract is the most common cause of disease in childhood and adulthood. The formation of the intestinal microbiome begins in utero, and composition modification during life depends mainly on various genetic, nutritional, and environmental factors. The main cause of intestinal dysbiosis is improper nutrition due to a short period of breastfeeding, insufficient intake of fresh fruits and vegetables, and/or consumption of a large amount of processed food. The benefits of a diet based on grains, legumes, fruits, and vegetables are reflected in reducing the risk of cancer, cardiovascular diseases, myocardial infarction, stroke, rheumatoid arthritis, high blood pressure, asthma, allergies, and kidney stones. Anaerobic fermentation of fibers produces short-chain fatty acids (SCFA) that have an anti-inflammatory role and great importance in shaping the intestinal microbiota. Factors associated with high fiber in a plant-based diet promote increased insulin sensitivity. Insulin and insulin-like growth factor 1 (IGF-I) act as promoters of most normal and pre-neoplastic tissues. Conclusion: A plant-based diet high in fiber prevents disease by creating metabolites in the gut that reduce oxidative stress.

Therapeutic Effects of Liposomal Resveratrol in the Mitigation of Diabetic Nephropathy via Modulating Inflammatory Response, Oxidative Stress, and Apoptosis.

An important factor in the development of diabetes and its associated consequences is prolonged chronic hyperglycemia, which weakens the antioxidant defense system and produces reactive oxygen species. Phytochemicals have been found to scavenge free radicals and exhibit antioxidant effects necessary to increase insulin sensitivity and reduce the development of diabetes-related complications. Current treatments for managing diabetes and diabetic nephropathy are often not very effective and come with several limitations and side effects. Resveratrol, for example, has shown therapeutic potential in mitigating kidney damage induced by high glucose levels, but its short bioavailability is a significant limitation. This accentuates the need for alternatives that not only improve the disease but also reduce the side effects associated with treatment. To enhance the therapeutic efficacy of resveratrol, we investigated the protective effects of liposomal resveratrol (LR) in a streptozotocin-induced diabetic rat model at doses of 20 and 40mg/kg. We compared the impact of LR to that of resveratrol alone (at a dose of 40mg/kg) on various parameters, including serum levels of biochemical markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress indices, and apoptotic markers. LR, as a highly absorbable and metabolized form of resveratrol, has demonstrated beneficial effects in diabetic rats. Administered at both 20mg/kg and 40mg/kg dosages over a 5-week period, it demonstrated notable efficacy in alleviating inflammation. This was accomplished by diminishing the levels of pro-inflammatory mediators, TNF-α and IL-6, through the inhibition of NF-κB translocation. Additionally, LR influenced apoptotic markers, specifically caspase, BCL-2, and BAX. Furthermore, it enhanced the expression of key antioxidant enzymes such as catalase and glutathione peroxidase while significantly lowering malondialdehyde levels. These significant biochemical and immunological protective effects correlated with improved histological integrity and overall kidney architecture. Notably, resveratrol alone was not as effective as LR in restoring kidney function, highlighting its potential as a therapeutic candidate for the treatment of diabetic nephropathy. However, more in-depth studies are needed to explore its mechanism of action and improved bioavailability.

Combined diet and exercise training decreases serum lipids associated with insulin resistance.

Circulating lipids are linked with insulin resistance and increased cardiovascular disease risk. We previously reported that dihydroceramides, a specific type of sphingolipid, are elevated in insulin-resistant individuals; however, little is known regarding whether insulin-sensitizing lifestyle interventions can improve profiles of sphingolipids and other lipid species. A total of 21 individuals with obesity participated in a 3-month lifestyle intervention of combined weight loss and exercise training. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps, and serum lipidomics was conducted. Following the intervention, BMI was significantly reduced by 10%; VO2peak and insulin sensitivity increased by 12% and 57%, respectively; and total serum triacylglycerol (TAG), diacylglycerol, dihydroceramides, sphingosine-1-phosphate, and sphinganine-1-phosphate were significantly reduced, as were specific species of dihydroceramides (C18:0 and C24:1). Individuals with higher preintervention TAG concentrations had significant decreases in serum lipids, which were not significantly changed in individuals with lower preintervention TAG. These data show that serum sphingolipid species previously linked to insulin resistance in humans can be reduced with insulin-sensitizing lifestyle interventions. Furthermore, individuals with elevated serum TAG may significantly benefit from lifestyle interventions that increase insulin sensitivity due to a greater decrease in serum lipids related to insulin resistance.

Effects of age and diet on triglyceride metabolism in mice

Both age and diet can contribute to alterations in triglyceride metabolism and subsequent metabolic disease. In humans, plasma triglyceride levels increase with age. Diets high in saturated fats can increase triglyceride levels while diets high in omega-3 fatty acids decrease triglyceride levels. Here we asked how age and long-term diet altered triglyceride metabolism in mice. We fed male and female C57Bl/6 mice a low-fat diet, a western diet (WD), or a diet high in polyunsaturated and omega-3 fatty acids (n3D) for up to 2 years. We measured survival, body composition, plasma triglyceride levels, chylomicron clearance, and oral fat, glucose, and insulin tolerance. Triglyceride levels in mice did not increase with age, regardless of diet. Oral fat tolerance increased with age, while chylomicron clearance remained unchanged. Decreased survival was observed in WD-fed mice. Interestingly, n3D-fed mice diet gained more lean mass and had lower insulin levels than WD-fed or LFD-fed mice. Moreover, triglyceride uptake into the hearts of n3D-fed mice was strikingly higher than in other groups. Our data indicate that in C57Bl/6 mice, age-induced changes in triglyceride metabolism differ from those observed in humans. Mice, like humans, appeared to have decreased fat absorption with age, but in mice plasma triglyceride clearance did not decrease with age, resulting in lower plasma triglyceride levels and improved fat tolerance with age. Although a chronic diet high in omega-3 fatty acids increased insulin sensitivity and triglyceride uptake specifically into the heart, how these observations are connected is unclear.