Reduce Insulin Resistance Research Articles

High dietary antioxidant index associated with reduced insulin resistance in female Mexican children and adolescents

Antioxidant intake is inversely associated with different health outcomes; however, its association with insulin resistance (IR) has not been well documented. We hypothesized that the Dietary Antioxidant Index (DAI) is inversely associated with IR in Mexican children and adolescents. A cross-sectional analysis was performed using data from the Health Workers Cohort Study. A total of 830 children and adolescents aged 7 to 18 years were enrolled. The DAI was evaluated in three categories defined by tertiles using a semiquantitative food frequency questionnaire. IR was defined using previously reported cutoff points in the homeostasis model assessment. This association was evaluated using a multiple logistic regression model. Stratified analysis was performed using body mass index and sex. The prevalence of IR based on the DAI categories (low, medium, high) was 23.8%, 24.2%, and 15.3%, respectively. The IR odds ratio (OR) for participants in the highest DAI category was 0.49 (95% confidence interval [CI]: 0.30-0.80). Notably, female Children and Adolescents in the highest DAI category had significantly lower odds of developing IR than those in the lowest DAI category (OR 0.54, 95% CI 0.29-0.98). Participants with overweight/obesity showed a similar association (OR 0.37, 95% CI 0.18-0.76). These results suggest that the DAI is inversely associated with IR, particularly in females, highlighting the potential role of antioxidants in preventing IR. This underscores the need to establish recommendations for antioxidant consumption in female children and adolescents.

Inhibition of Adipocyte-Derived FABP4 Reduces Adipocyte Inflammation, Improves Angiogenesis, and Facilitates Wound Healing in Metabolic Dysfunctions

Dermal white adipose tissue may participate in the wound healing process. Obesity-mediated chronic low-grade inflammation impairs wound healing by suppressing vascularity. Given that fatty-acid-binding protein (FABP) 4 is upregulated in the skin tissue of obese animals, this study aimed to investigate the effects of FABP4 inhibition on wound healing in high-fat-diet (HFD)-induced metabolic dysfunction mice in vivo. The interaction between adipocyte-derived FABP4 and vascular endothelial cell function was also investigated. In HFD-induced metabolic dysfunction mice, FABP4 inhibition increased angiogenesis and facilitated wound healing with reduced wound inflammation. FABP4 inhibition not only attenuated systemic inflammation, decreased body weight, and reduced insulin resistance, but also improved the sizes of adipocytes and hypoxic conditions in dermal white adipose tissue. The in vitro hypoxia was used to induce adipocyte inflammation, and the supernatants from hypoxia-stimulated adipocytes impaired the function and angiogenetic capability of human dermal microvascular endothelial cells. Both of them were improved by FABP4 inhibition. Altogether, FABP4 inhibition reduced systemic and adipocyte inflammation, improved vascular endothelial cell function, and facilitated wound healing in metabolic dysfunctions. Given the complex involvement of wound healing, future studies may be required to validate FABP4 as a potential therapeutic target for wound repair in metabolic dysfunctions.

Potential Effect of Curcumin in Lowering Blood Glucose Level in Streptozotocin-Induced Diabetic Rats.

The prevalence of diabetes mellitus has significantly increased, with 537 million individuals living with diabetes in 2021. Curcumin, a natural compound present in turmeric, has anti-inflammatory and antioxidant properties that aid in controlling diabetes. Curcumin can lower blood glucose levels, increase pancreatic cell function, and reduce insulin resistance. The pathophysiology of diabetes involves oxidative stress and endoplasmic reticulum stress, which can lead to cell death. This study aimed to evaluate the antidiabetic activity of curcumin in rats by administering it for a month and evaluating pancreatic tissue histology. STZ-induced diabetic rats were fed a high-fat diet containing glibenclamide, 200 mg/kg body weight (BW) curcumin, 400 mg/kg BW curcumin, or a placebo for 4 weeks. After intervention, blood glucose levels were measured, and the pancreatic tissue was examined. Blood glucose levels were measured at 0, 2, 4, 6, and 8 h. One-way ANOVA was performed to measure the mean difference among the groups at 0, 2, 4, 6, and 8 h of observation, which reported a statistically significant difference (p < 0.05). The blood glucose levels decreased after 4 h in the group receiving curcumin. Histological evaluation of the pancreas showed slight hydropic degeneration after 4 weeks of curcumin treatment. Our study indicates that curcumin has a beneficial effect in diabetic rats by reducing blood glucose levels and a protective effect on the pancreas.

P059 IDENTIFYING PREDICTORS OF EARLY-ONSET HYPERTENSION IN MIDDLE-AGED INDIVIDUALS WITH OBESITY

Background: Hypertension is a leading risk factor for cardiovascular diseases, with obesity being one of its primary modifiable predictors. This longitudinal study aims to identify early predictors of developing hypertension in middle-aged individuals with obesity, contributing to targeted prevention strategies. Methods: A cohort of 112 middle-aged participants (mean age 48.6 ± 10.8 years, 55% male) with a body mass index (BMI) ≥ 30 kg/m^2 but without hypertension at baseline were followed for an average of 5.8 ± 2.4 years. The study sought to determine significant predictors for the development of hypertension, including demographic variables, lifestyle factors, and biochemical markers. Cox proportional hazards regression models were employed to estimate hazard ratios (HR) for the development of hypertension, with Kaplan-Meier analysis used to visualize time-to-event outcomes. Statistical significance was determined by p-values &lt; 0.05. Results: Over the follow-up period, 34% of participants developed hypertension. Kaplan-Meier analysis indicated a significant difference in hypertension-free outcomes based on baseline insulin resistance levels and waist-to-hip ratio (WHR) (p &lt; 0.01). Cox regression analysis revealed that insulin resistance (HR = 1.12 per unit increase, 95% CI: 1.06-1.19, p = 0.001) and WHR (HR = 2.48 for the highest quartile vs. lowest, 95% CI: 1.32-4.67, p = 0.005) were independent predictors of developing hypertension. Furthermore, a sedentary lifestyle was associated with an increased risk (HR = 1.89, 95% CI: 1.01-3.54, p = 0.046), whereas dietary factors did not show a significant relationship after adjusting for other variables. Conclusion: This study identifies insulin resistance and WHR as significant predictors of early-onset hypertension among middle-aged individuals with obesity, with lifestyle factors also playing a crucial role. These findings underscore the importance of targeted interventions focusing on reducing insulin resistance and central obesity, along with promoting physical activity, to prevent the development of hypertension in this high-risk population.

Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-Aged and Elderly: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Nicotinamide Mononucleotide (NMN) has gained attention as a precursor to Nicotinamide Adenine Dinucleotide (NAD+) in recent years, commonly utilized in anti-aging therapies. The anti-aging effects of NMN on muscle and liver functions in middleaged and elderly people are still unclear. Based on available randomized controlled trials, we conducted a meta-analysis to evaluate the impact of NMN on muscle and liver functions in middle-aged and elderly individuals. We conducted searches on three electronic databases (PubMed, Embase, Web of Science) for randomized controlled trials involving NMN interventions in middle-aged and elderly populations. Through the Cochrane Handbook, we assessed the specific methodological quality. All statistical analyses were obtained by Stata15, and statistical significance was set as P<0.05. There were 412 participants from 9 studies in this meta-analysis. Based on changes in gait speed (SMD: 0.34 m/s, 95%CI [0.03, 0.66] p = 0.033), NMN had significant effects on muscle mass. Moreover, NMN had a better effect on ALT (SMD: -0.29 IU/L, 95%CI [-0.55, -0.03] p = 0.028). Subgroup analysis indicated that administering a small dose of NMN exerted the most prominent impact on Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). NMN has positive efficacy in enhancing muscle function, reducing insulin resistance and lowering aminotransferase levels in middle-aged and elderly individuals. NMN is an encouraging and considerable drug for anti-aging treatment.

Hypoglycemic effect of orally administered resistant dextrins prepared with different acids on type 2 diabetes mice induced by high-fat diet and streptozotocin

A comparative study was performed to investigate the physicochemical properties and protective effects of hydrochloric acid-resistant dextrin (H-RD), citric acid-resistant dextrin (C-RD) and tartaric acid-resistant dextrin (T-RD) on the metabolic disorders and intestinal microbiota for type 2 diabetes mellitus (T2DM) mice. T-RD had the minimum molecular weight, with the highest short chain (DP 6–12) proportion and resistant starch content. After 4-week intervention with the three resistant dextrins, the body weight and fasting blood glucose of T2DM mice were improved significantly, accompanied by the reduction of serum indexes (TG, TC, LDL-C, ALT, AST, CRE, BUN, FINS, and GSP), but the serum HDL-C and liver glycogen levels increased. Among the three RDs intervention groups, T-RD showed the most significant improvement, followed by C-RD and finally H-RD. The 16 s rDNA results indicated that oral administration of resistant dextrins favored the proliferation of specific gut microbiota, including Faecalibaculum, Parabacteroides and Dubosiella, and reduced the ratio of Firmicutes/Bacteroidota, which is beneficial for reducing insulin resistance. Herein, the findings supported that the resistant dextrins exhibited a remission effect on T2DM, providing a basis for the development of functional food adjuvants for T2DM treatment.

Study of the Effects of Deuterium-Depleted Water on the Expression of GLUT4 and Insulin Resistance in the Muscle Cell Line C2C12.

Deuterium-depleted water (DDW) is used in the treatment of many diseases, including cancer and diabetes. To detect the effect of DDW on gene expression and activation of the insulin-responsive transporter GLUT4 as a mechanism for improving the pathology of diabetes, we investigated the GLUT4 expression and glucose uptake at various concentrations of DDW using the myoblast cell line C2C12 differentiated into myotubes. GLUT4 gene expression significantly increased under deuterium depletion, reaching a maximum value at a deuterium concentration of approximately 50 ppm, which was approximately nine times that of natural water with a deuterium concentration of 150 ppm. GLUT4 protein also showed an increase at similar DDW concentrations. The membrane translocation of GLUT4 by insulin stimulation reached a maximum value at a deuterium concentration of approximately 50-75 ppm, which was approximately 2.2 times that in natural water. Accordingly, glucose uptake also increased by up to 2.2 times at a deuterium concentration of approximately 50 ppm. Drug-induced insulin resistance was attenuated, and the glucose uptake was four times higher in the presence of 10 ng/mL TNF-α and three times higher in the presence of 1 μg/mL resistin at a deuterium concentration of approximately 50 ppm relative to natural water. These results suggest that DDW promotes GLUT4 expression and insulin-stimulated activation in muscle cells and reduces insulin resistance, making it an effective treatment for diabetes.

Extraction, Characterization, and Nutraceutical Potential of Prosthechea karwinskii Orchid for Insulin Resistance and Oxidative Stress in Wistar Rats.

Prosthechea karwinskii is an endemic orchid of Mexico with cultural significance for its ornamental, food, religious, and medicinal uses. In traditional medicine, diabetic patients use the leaves of this plant to lower glucose levels. The present study evaluated the effect of P. karwinskii leaves extract on the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in a model of obese rats with insulin resistance for its nutraceutical potential to reduce insulin resistance and oxidative stress. Obesity and insulin resistance were induced with 40% sucrose in water for 20 weeks. Four groups (control rats, obese rats, obese rats administered the extract, and obese rats administered metformin) were evaluated. Extract compounds were identified by UHPLC-ESI-qTOF-MS/MS. Glucose, insulin, triglyceride, and insulin resistance indices (HOMA-IR and TyG), as well as the activity of the antioxidant enzymes, increased in rats in the obese group. Administration of P. karwinskii extract and metformin reduced glucose, insulin, triglyceride, and insulin resistance indices and antioxidant enzyme activity to values similar to those of the control group. Therefore, this study shows the nutraceutical potential of P. karwinskii extract as an ingredient in the formulation of dietary supplements or functional foods to help treat diseases whose pathophysiology is related to oxidative stress and insulin resistance.

Theaflavins mitigate diabetic symptoms in GK rats by modulating the INSR/PI3K-Akt/GSK-3 pathway and intestinal microbiota

Dietary management and interventions are crucial in the clinical management of diabetes. Numerous active dietary components in black tea have demonstrated positive effects on blood glucose levels and metabolic functions. However, limited research has explored the potential of theaflavins (TF), polyphenols in black tea, for diabetes management. In this study, high-purity TF was administered to Goto–Kakizaki (GK) diabetic model rats for four weeks to investigate its impact on diabetic pathology and analyze the underlying mechanisms through liver transcriptomics, hepatocyte metabolomics, and gut microbiome analysis. The findings indicated that continuous administration of TF (100 mg/kg) significantly suppressed blood glucose levels, reduced insulin resistance, and decreased the expression of oxidative stress indicators and inflammatory factors in GK rats. Further analysis revealed that TF might alleviate insulin resistance by improving hepatic glycogen conversion and reducing hepatic lipid deposition through modulation of key pathways, such as peroxisome proliferator-activated receptors and PI3K/AKT/GSK-3 pathways within the liver, thereby ameliorating diabetic symptoms. Additionally, TF intake facilitated the restoration of the intestinal microbial community structure by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. It also reduced endotoxin lipopolysaccharide production, thereby lowering the chances of insulin resistance development and enhancing its efficacy in regulating blood glucose levels. These findings offer a novel perspective on the potential of black tea and its active constituents to prevent and treat diabetes and other metabolic disorders, providing valuable references for identifying and applying active dietary components from tea.

Formononetin attenuates hepatic injury in diabetic mice by regulating macrophage polarization through the PTP1B/STAT6 axis

BackgroundFormononetin (FNT) is an isoflavone known for its anti-inflammatory properties and has been shown to reduce insulin resistance in Type 2 Diabetes Mellitus (T2DM). However, its effects and the underlying mechanisms in diabetic liver injury remain largely unexplored. MethodsWe established a T2DM-induced liver injury mouse model by feeding high-fat diet, followed by injecting streptozotocin. The mice were then treated with FNT and the liver function in these mice was assessed. Macrophage markers in FNT-treated T2DM mice or human THP-1 cells were evaluated using flow cytometry, RT-qPCR, and Western blotting. The expression of PTP1B and STAT6 in mouse liver tissues and THP-1 cells was analyzed. Molecular docking predicted the interaction between PTP1B and STAT6, which was validated via co-immunoprecipitation (Co-IP) and phos-tag analysis. Microscale thermophoresis (MST) assessed the binding affinity of FNT to PTP1B. ResultsFNT treatment significantly ameliorated blood glucose levels, hepatocyte apoptosis, inflammatory response, and liver dysfunction in T2DM mice. Moreover, FNT facilitated M2 macrophage polarization in both T2DM mice and high glucose (HG)-induced THP-1-derived macrophages. The PTP1B/STAT6 axis, deregulated in T2DM mice, was normalized by FNT treatment, which counteracted the T2DM-induced upregulation of PTP1B and downregulation of phosphorylated STAT6. Molecular docking and subsequent analyses revealed that PTP1B binds to and dephosphorylates STAT6 at the S325A site. In contrast, FNT strongly binds to PTP1B and influences its expression at the K116A site, promoting M2 polarization of THP-1 cells via downregulation of PTP1B. ConclusionFormononetin mitigates diabetic hepatic injury by fostering M2 macrophage polarization via the PTP1B/STAT6 axis.

Dorzagliatin: A Breakthrough Glucokinase Activator Coming on Board to Treat Diabetes Mellitus.

Dorzagliatin, an innovative dual-acting allosteric oral glucokinase activator that targets glucose homeostasis and insulin resistance, has gained approval for treating type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The effectiveness of existing antidiabetic treatments in enhancing beta cell (β-cell) activity is restricted. Currently, there are no satisfactory medications available to address the fundamental deficiency in glucose sensing for glucokinase-maturity-onset diabetes of the young (GCK-MODY), which is caused by mutations in the glucokinase gene; researchers have embarked on glucokinase activators. Dorzagliatin enhances the affinity of glucokinase for glucose and glucose-sensing capacity, improves β-cell function, and reduces insulin resistance. Two phase 3 studies, an adjunct trial of dorzagliatin with metformin for T2DM patients and a monotherapy trial for drug-naïve T2DM patients, are key clinical trials that have shown a favorable safety and tolerability profile. They also demonstrated a rapid, sustained reduction in glycated hemoglobin (HbA1c) and a significant decrease in postprandial blood glucose. This review will summarize the substantial clinical evidence supporting the safety and efficacy of dorzagliatin in treating diabetes mellitus (DM) and clarify the molecular mechanisms underlying its action.

Exploring the Contribution of Traditional Medicinal Herbs in ManagingPolycystic Ovary Syndrome: A Comprehensive Review

: Polycystic ovary syndrome (PCOS) is a significant gynecological disorder that commonly affects women of reproductive age. Disturbances in the production and metabolism of androgens and estrogens mark the condition. Due to the rising occurrence of PCOS and its related physical and psychological issues, along with the role of sex hormone fluctuations in its development, the use of marketed drugs is effective in treating PCOS but is accompanied by negative consequences. Consequently, a significant number of individuals with PCOS are opting for natural remedies due to the positive therapeutic effects associated with natural medications and the constraints of allopathic treatments. This review aims to assess the impact of different herbs on alterations in sex hormone levels in the bloodstream and ovarian tissue. By conducting a comprehensive literature search utilizing databases such as PubMed, Google Scholar, and Crossref, we have gathered and analyzed pertinent information regarding the efficacy of herbal remedies in combating PCOS. Based on the available evidence, herbs consisting of phytoestrogens can potentially reduce insulin resistance, hyperandrogenism, and ovarian weight while facilitating ovulation. This review explores the importance of herbal remedies in addressing PCOS, elucidates their mechanisms of action, and examines the therapeutic uses of specific herbal medications to treat PCOS. Human studies on medicinal herbs for managing Polycystic Ovary Syndrome (PCOS) need extended durations for a comprehensive evaluation of both safety and efficacy, emphasizing the necessity for more long-term research. It is anticipated that this comprehensive review will serve as a valuable resource for researchers studying the effect of herbs on PCOS, providing them with valuable insights and information.

Pulmonary administration of cross-linked chitosan nanoparticles of genistein for regulating blood glucose

The research study focused on the development and characterization of sustained release formulation of genistein (GEN)-loaded chitosan (CS) nanoparticles to deliver in the form of dry powder inhaler (DPI) via pulmonary route to offer higher stability and anti-diabetic activity. The GEN-loaded nanoparticles were prepared by cross-linking reaction of CS and sodium hexametaphosphate (SHMP). The optimized formulation displayed particle size (PS) of 684.2 ± 26.5 nm, zeta potential (ZP) of 19.6 ± 4.50 mV, % entrapment efficiency (% EE) of 87.33 ± 8.46 % and drug release profile of 85.48 ± 5.50 % for 48 h. The in-vivo studies exhibited a superior sustained release formulation of GEN in the regulation of blood glucose levels (BGLs). The powder showed the emitted fraction (EF) of 86.76 % and effective inhalation index (EI) of 85.41 %. The reduction of BGLs (85 %) was observed in the diabetic group. This might be due to the inhibition of proliferation of pancreatic β-cells (growth factor inhibition targeting cAMP and ERK1/2 pathway), antioxidative activity, reducing insulin resistance, and the adipose tissue mass and alteration of the hepatic glucose metabolism. Hence, these results proved the delivery of GEN in the form of DPI system as a favorable route for treating type-1 diabetes mellitus with a longer duration of action.

Structural characterization and hypoglycemic effect of polysaccharides of Polygonatum sibiricum.

Polygonatum sibiricum polysaccharide (PSP) was extracted and purified from raw material obtained from P. sibiricum. The structural features of PSP were investigated by Congo red, circular dichroism spectrum, high-performance gel permeation chromatography, scanning electron microscope, atomic force microscope, ultraviolet spectroscopy, and Fourier transform infrared spectroscopy analysis. In vitro simulations were conducted to investigate the kinetics of PSP enzyme inhibition. Moreover, a type II diabetes mouse model (T2DM) with streptozotocin-induced insulin resistance was established, and the indexes of lipid quadruple, insulin resistance index, oral glucose tolerance (OGTT), organ index, and pancreatic morphology of model mice were measured. The results showed that PSP mainly consists of monosaccharides, such as mannose, glucose, galactose, xylose, and arabinose. It also has a β-glycosidic bond of a pyranose ring and an irregular reticulated aggregated structure with a triple helix. In vitro enzyme inhibition assays revealed that PSP acts as a reversible competitive inhibitor of α-glucosidase and α-amylase. Furthermore, PSP was found to reduce insulin resistance index, increase OGTT and serum insulin levels, decrease free fatty acid content to improve lipid metabolism, and lower glycated serum protein content to enhance glucose metabolism in T2DM mice, thereby leading to a reduction in blood glucose concentration. Additionally, PSP exhibited reparative effects on the damaged liver tissue cells and pancreatic tissue in T2DM mice. The experiment results provide a preliminary basis for the therapeutic mechanism of PSP about type II diabetes and a theoretical reference for application in food and pharmaceutical development.

Thiazolidinedione as a Promising Medicinal Scaffold for the Treatment of Type 2 Diabetes.

Thiazolidinediones, also known as glitazones, are considered as biologically active scaffold and a well-established class of anti-diabetic agents for the treatment of type 2 diabetes mellitus. Thiazolidinediones act by reducing insulin resistance through elevated peripheral glucose disposal and glucose production. These molecules activate peroxisome proliferated activated receptor (PPARγ), one of the sub-types of PPARs, and a diverse group of its hybrid have also shown numerous therapeutic activities along with antidiabetic activity. The objective of this review was to collect and summarize the research related to the medicinal potential, structure-activity relationship and safety aspects of thiazolidinedione analogues designed and investigated in type 2 diabetes during the last two decades. The mentioned objective was achieved by collecting and reviewing the research manuscripts, review articles, and patents from PubMed, Science Direct, Embase, google scholar and journals related to the topic from different publishers like Wiley, Springer, Elsevier, Taylor and Francis, Indian and International government patent sites etc. Results: The thiazolidinedione scaffold has been a focus of research in the design and synthesis of novel derivatives for the management of type 2 diabetes, specifically in the case of insulin resistance. The complications like fluid retention, idiosyncratic hepatotoxicity, weight gain and congestive heart failure in the case of trosiglitazone, and pioglitazone have restricted their use. The newer analogues have been synthesized by different research groups to attain better efficacy and less side effects. Thus, the potential of thiazolidinediones in terms of their chemical evolution, action on nuclear receptors, aldose reductase and free fatty acid receptor 1 is well established. The newer TZD analogues with better safety profiles and tolerability will soon be available in the market for common use without further delay.

The impact of malnutrition on secondary diabetes and calcific pancreatitis: A comprehensive review

Introduction: Malnutrition in low- and middle-income countries significantly impacts the development of secondary diabetes and calcific pancreatitis. Aim and Methods: This review summarizes the prevalence, characteristics, and findings from key studies over the past decade on the link between malnutrition and secondary diabetes, focusing on protein-deficient pancreatic diabetes (PDPD) and fibro-calculous pancreatic diabetes (FCPD). A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar for articles published between 1995 and 2023. Studies included were peer-reviewed articles focusing on the link between malnutrition and secondary diabetes, conducted in LMICs, and discussing the prevalence, clinical characteristics, and outcomes of PDPD and FCPD. Both observational and interventional studies were considered. Results: The review of studies revealed several key findings: · PDPD is characterized by lower C-peptide levels and varied responses to glibenclamide post-nutritional rehabilitation. · FCPD patients show rapid calcification, diminished exocrine and beta-cell function, and more severe exocrine deficiency compared to PDPD. · Both PDPD and FCPD patients often present with lower BMI and significant renal involvement. · Recent studies indicate improved nutritional status and prognosis of FCPD patients with enhanced medical care. · Insulin-requiring diabetes in Ethiopia is strongly linked with poor education, poverty markers, and childhood malnutrition. · Lean diabetes, linked to childhood malnutrition, is characterized by low-normal BMI, early onset, and rapid beta-cell failure. Discussion: The development of diabetes following early malnutrition can be attributed to several interconnected mechanisms involving metabolic, endocrine, and epigenetic factors. Early nutritional intervention trials are crucial to prevent glucose abnormalities and diabetes later in life. Studies highlight that improving early-life nutrition can enhance beta-cell function, reduce insulin resistance, and mitigate long-term metabolic dysfunction. Lean diabetes, linked to childhood malnutrition, presents unique challenges but can be addressed through targeted nutritional support. Conclusion: The review underscores the significant impact of malnutrition on the development of secondary diabetes and calcific pancreatitis in LMICs. Addressing malnutrition through early nutritional interventions is crucial to mitigate the risk of chronic conditions and improve metabolic health outcomes. Continued research and targeted public health strategies are essential to break the cycle of malnutrition and disease in vulnerable populations.

Long term administration of thiamine disulfide improves FOXO1/PEPCK pathway in liver to reduce insulin resistance in type 1 diabetes rat model

ObjectiveThe main objective of this study was to find if thiamine disulfide (TD) lowers blood glucose level and improves insulin resistance (IR) in liver and muscle in rats with chronic type 1 diabetes (T1DM) using euglycemic-hyperinsulinemic clamp technique. MethodsA total of fifty male Wistar rats were assigned to five groups consisted of: non-diabetic control (NDC), diabetic control (DC), diabetic treated with thiamine disulfide (D-TD), diabetic treated with insulin (D-insulin), and diabetic treated with both TD and insulin (D-insulin+TD). Diabetes was induced by a 60 mg/kg dose of streptozotocin. Blood glucose levels, pyruvate tolerance test (PTT), intraperitoneal glucose tolerance test (IPGTT), levels of glycosylated hemoglobin (HbA1c), glucose infusion rate (GIR), liver and serum lipid profiles, liver glycogen stores, liver enzymes ([ALT], [AST]), and serum calcium and magnesium levels. were evaluated. Additionally, gene expression levels of phosphoenolpyruvate carboxykinase (Pepck), forkhead box O1 (Foxo1), and glucose transporter type 4 (Glut4) were assessed in liver and skeletal muscle tissues. ResultsBlood glucose level was reduced by TD treatment. In addition, TyG index, HOMA-IR, serum and liver lipid profiles, HbA1c levels, and expressions of Foxo1 and Pepck genes were decreased significantly (P<0.05) in all the treated groups. However, TD did not influence Glut4 gene expression, but GIR as a critical index of IR were 5.0±0.26, 0.29±0.002, 1.5±0.07, 0.9±0.1 and 1.3±0.1 mg.min−1Kg−1 in NDC, DC, D-TD, D-insulin and D-insulin+TD respectively. ConclusionsTD improved IR in the liver primarily by suppressing gluconeogenic pathways, implying the potential use of TD as a therapeutic agent in diabetes.

New Chitosan-Based Co-Delivery Nanosystem for Diabetes Mellitus Therapy.

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders, with a major involvement of oxidative stress in its onset and progression. Pioglitazone (Pio) is an antidiabetic drug that mainly works by reducing insulin resistance, while curcumin (Cur) is a powerful antioxidant with an important hypoglycemic effect. Both drugs are associated with several drawbacks, such as reduced bioavailability and a short half-life time (Pio), as well as instability and poor water solubility (Cur), which limit their therapeutic use. In order to overcome these disadvantages, new co-delivery (Pio and Cur) chitosan-based nanoparticles (CS-Pio-Cur NPs) were developed and compared with simple NPs (CS-Pio/CS-Cur NPs). The NPs were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). In addition, the entrapment efficiency (EE) and loading capacity (LC), as well as the release profile, of the APIs (Pio and Cur) from the CS-APIs NPs in simulated fluids (SGF, SIF, and SCF) were also assessed. All the CS-APIs NPs presented a small particle size (PS) (211.6-337.4 nm), a proper polydispersity index (PI) (0.104 and 0.289), and a positive zeta potential (ZP) (21.83 mV-32.64 mV). Based on the TEM results, an amorphous state could be attributed to the CA-APIs NPs, and the TEM analysis showed a spherical shape with a nanometric size for the CS-Pio-Cur NPs. The FT-IR spectroscopy supported the successful loading of the APIs into the CS matrix and proved some interactions between the APIs and CS. The CS-Pio-Cur NPs presented increased or similar EE (85.76% ± 4.89 for Cur; 92.16% ± 3.79 for Pio) and LC% (23.40% ± 1.62 for Cur; 10.14% ± 0.98 for Pio) values in comparison with simple NPs, CS-Cur NPs (EE = 82.46% ± 1.74; LC = 22.31% ± 0.94), and CS-Pio NPs (EE = 93.67% ± 0.89; LC = 11.24% ± 0.17), respectively. Finally, based on the release profile results, it can be appreciated that the developed co-delivery nanosystem, CS-Pio-Cur NPs, assures a controlled and prolonged release of Pio and Cur from the polymer matrix along the GI tract.

Metabolic complications of psychotropic medications in psychiatric disorders: Emerging role of de novo lipogenesis and therapeutic consideration.

Although significant advances have been made in understanding the patho-physiology of psychiatric disorders (PDs), therapeutic advances have not been very convincing. While psychotropic medications can reduce classical symptoms in patients with PDs, their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). The mechanism(s) underlying these metabolic abnormalities is not clear; however, lipid/fatty acid accumulation due to enhanced de novo lipogenesis (DNL) has been shown to reduce membrane fluidity, increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities. Intriguingly, emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity, diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs. In support of this, several adjunctive drugs comprising of anti-oxidants and anti-inflammatory agents, that are used in treating PDs in combination with psychotropic medications, have been shown to reduce insulin resistance and development of NAFLD. In conclusion, the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities, and a new avenue for translational research and therapeutic drug designing in PDs.

Orlistat and Metformin Effectively Reduce Pancreatic Dysfunction, Insulin Resistance and Blood Glucose Levels in Male Rats Experimentally Induced with Obesity

Orlistat and Metformin Effectively Reduce Pancreatic Dysfunction, Insulin Resistance and Blood Glucose Levels in Male Rats Experimentally Induced with Obesity