Reduced Glucose Levels Research Articles

Mediterranean Diet and Olive Oil Redox Interactions on Lactate Dehydrogenase Mediated by Gut Oscillibacter in Patients with Long-COVID-19 Syndrome

Chronic viral inflammation is associated with oxidative stress and changes in gut microbiota. The Mediterranean diet (MD), with recognized anti-inflammatory and antioxidant properties, modulates gut microorganisms, specifically on the interaction between extra virgin olive oil, a key component of the MD with well-documented antioxidant effects. This study investigated the influence of adherence to MD and antioxidant-rich foods (extra virgin olive oil) on biochemical, inflammatory, and microbiota profiles in patients with chronic inflammation defined as a prolonged inflammatory response due to immune dysregulation following the acute phase of the viral infection. Participants were classified into low (n = 54) and high (n = 134) MD adherence groups (cut-off of 7 points based on previous studies utilizing the same threshold in the assessment of MD adherence). Gut microbiota was sequenced using the 16S technique, and the adherence to MD was assessed using a validated questionnaire for a Spanish population. High adherence to the MD was linked to significant improvements in inflammatory and oxidative stress markers, including reductions in LDL-cholesterol, glucose, and lactate dehydrogenase (LDH) levels, an indicative of redox balance, as well as a significant higher consumption of antioxidant foods. Moreover, gut microbiota analysis revealed distinct compositional shifts and a lower abundance of the Oscillibacter genus in the high adherence group. Notably, a significant interaction was observed between MD adherence and extra virgin olive oil consumption, with Oscillibacter abundance influencing LDH levels, suggesting that the MD antioxidant properties may modulate inflammation through gut microbiota-mediated mechanisms. These findings provide new evidence that adherence to the Mediterranean diet can reduce inflammatory markers in patients with long-COVID-19, a population that has not been extensively studied, while also highlighting the potential role of the bacterial genus Oscillibacter in modulating this effect.

Engineering Supramolecular Nanofiber Depots from a Glucagon-Like Peptide-1 Therapeutic.

Diabetes and obesity have emerged as major global health concerns. Glucagon-like peptide-1 (GLP-1), a natural incretin hormone, stimulates insulin production and suppresses glucagon secretion to stabilize and reduce blood glucose levels and control appetite. The therapeutic use of GLP-1 receptor agonists (e.g., semaglutide) has transformed the standard of care in recent years for treating type 2 diabetes and reversing obesity. The native GLP-1 sequence has a very short half-life, and therapeutic advances have come from molecular engineering to alter the pharmacokinetic profile of synthetic GLP-1 receptor agonists to enable once-weekly administration, reduce the frequency of injection, and improve adherence. Efforts to further extend this profile would offer additional convenience or enable entirely different treatment modalities. Here, an injectable GLP-1 receptor agonist depot is engineered through integration of a prosthetic self-assembling peptide motif to enable supramolecular nanofiber formation and hydrogelation. This supramolecular GLP-1 receptor agonistic (PA-GLP1) offers sustained release in vitro for multiple weeks, supporting long-lasting therapy. Moreover, in a rat model of type 2 diabetes, a single injection of the supramolecular PA-GLP1 formulation achieved sustained serum concentrations for at least 40 days, with an overall reduction in blood glucose levels and reduced weight gain, comparing favorably to daily injections of semaglutide. The general and modular approach is also extensible to other next-generation peptide therapies. Accordingly, the formation of supramolecular nanofiber depots offers a more convenient and long-lasting therapeutic option to manage diabetes and treat metabolic disorders.

Health Benefits of Yerba Mate Consumption on Cardiovascular Health

Background: Yerba mate is a Paraguayan kind of herbal tea prepared from the dried and roasted leaves of trees called Ilex paraguariensis St. Hill. It is known for high content of polyphenols, methylxanthines and saponins. According to the studies products rich in those nutrients may have a positive influence on the humans cardiovascular health. Materials and methods: We reviewed publications obtained from PubMed and Google Scholar. Articles were selected based on keywords such “yerba mate’’, “Ilex paraguariensis’’, “cardiovascular diseases’’. For the final analysis, qualified articles were published from 2005 to 2024. Results: Confirming positive impact on serum lipid levels individuals using mate tea. Long – term positive influence on blood pressure. Moreover subjects with obesity took advantages of Yerba beverage by decreasing waist-to-hip ratio. Patients with diabetes were observed to have a significant reduction in fasting plasma glucose level and HbA1c concentration. Conclusions: Most of the cited researches support the hypothesis of benefits coming from drinking mate infusions for patients with elevated lipid serum levels, obesity, high blood pressure and type 2 diabetes mellitus. All of mentioned health issues can lead to the cardiovascular problems therefore using mate infusions can prevent CVDs. Taking everything into consideration, medical professionals might recommend Yerba mate tea for their patients especially as a replacement of a coffee.

Dietary Restriction of Advanced Glycation End-Products (AGEs) in Patients with Diabetes: A Systematic Review of Randomized Controlled Trials

Advanced Glycation End Products (AGEs) are formed through non-enzymatic reactions between reducing sugars and proteins, nucleic acids or lipids (for example through hyperoxidation). In diabetes, elevated glucose levels provide more substrate for AGEs formation. AGEs can also be ingested through the diet from foods cooked at high temperatures, or containing much sugar. The present work aimed to review all published randomized controlled trials (RCT) on low-dietary AGE (L-dAGEs) interventions in patients with diabetes. Pubmed, Scopus and Cochrane databases were searched (until 29 February 2024) with appropriate keywords (inclusion criteria: RCT, patients with diabetes, age > 18 years, outcomes related to inflammation, glucose, and lipids; exclusion criteria: non-RCTs, case-series, case reports and Letter to the Editor, or animal studies). The present review was registered to the Open Science Framework (OSF). From 7091 studies, seven were ultimately included. Bias was assessed with the updated Cochrane Risk of Bias tool. A reduction in circulating AGEs was documented in 3/3 studies. No particular differences were documented in glycemic parameters after a L-dAGEs diet. Reductions in glucose levels were observed in one out of six studies (1/6), while HbA1c and HOMA did not change in any study (0/6 and 0/3, correspondingly). Lipid profile also changed in one out of four studies (1/4). More consistent results were observed for oxidative stress (beneficial effects in 3/3 studies) and inflammatory markers (beneficial effects in 4/4 studies). Other athero-protective effects, such as adiponectin increases, were reported. Limitations included the small sample size and the fact that dietary and physical activity habits were not considered in most studies. In conclusion, a L-dAGEs pattern may minimize AGEs accumulation and have beneficial effects on oxidative stress and inflammation indices, while its effects on glycemic and lipemic parameters are inconsistent and modest in patients with diabetes.

Metabolic Effects of Liposuction on Glucose and Insulin Homeostasis with and Without Abdominal Fat Removal.

Liposuction is a common cosmetic procedure aimed at addressing localized fat deposits. While metabolic disruptions associated with adiposity are well documented, the specific impacts of liposuction on metabolic parameters remain unclear. Seventeen individuals underwent liposuction inclusive of the abdominal area, while eleven underwent liposuction excluding the abdomen. Metabolic parameters including glucose, insulin, HOMA-IR, HbA1c, and C-peptide levels were measured preoperatively and postoperatively at 1, 3, and 6 months. Both groups exhibited significant postoperative reductions in glucose, insulin, HOMA-IR, HbA1c, and C-peptide levels. However, the abdominal liposuction group demonstrated more pronounced reductions of these variables. These findings suggest that addressing abdominal adiposity may provide greater metabolic benefits following liposuction. Further research is warranted to explore the long-term sustainability and clinical implications of these metabolic improvements with additional markers. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Soluble receptors for advanced glycation endproducts are predictors of insulin sensitivity and affected by weight loss

BackgroundMice experiments have underscored the efficacy of pharmacological inhibition of advanced glycation endproducts (AGEs) through the use of soluble receptors for advanced glycation endproducts (sRAGE) in mitigating obesity-linked metabolic disruptions and insulin resistance. However, human studies have presented conflicting findings regarding the correlation between circulating sRAGE levels and insulin resistance, as well as glucose tolerance. Here, we aimed to delve deeper into the relationship between sRAGE levels and systemic insulin sensitivity.MethodsPlasma sRAGE levels, hyperinsulinemic-euglycemic clamp, and continuous glucose monitoring were measured in two independent cross-sectional case-control studies [cohort 1 (n = 180) and cohort 2 (n = 124)]. In addition, a subgroup of 42 participants with obesity were followed for 12 months. In 14 of these participants, weight loss was achieved through bariatric surgery intervention.ResultsOur results revealed a significant association between plasma sRAGE levels and both insulin sensitivity and glycemic control parameters, even after adjustments for age, sex, and BMI. Furthermore, longitudinal analysis demonstrated that interventions aimed at weight loss led to reductions in fasting glucose and HbA1c levels, concurrently with increases in sRAGE levels.ConclusionsThese findings underscore that sRAGE levels were strongly associated with insulin sensitivity and glycemic control, suggesting a possible role of sRAGE in preserving insulin sensitivity and maintaining glycemic control, which should be confirmed in further studies.

Unravelling Different Water Management Strategies in Three Olive Cultivars: The Role of Osmoprotectants, Proteins, and Wood Properties

Understanding the responses of olive trees to drought stress is crucial for improving cultivation and developing drought-tolerant varieties. Water transport and storage within the plant is a key factor in drought-tolerance strategies. Water management can be based on a variety of factors such as stomatal control, osmoprotectant molecules, proteins and wood properties. The aim of the study was to evaluate the water management strategy under drought stress from an anatomical and biochemical point of view in three young Italian olive cultivars (Giarraffa, Leccino and Maurino) previously distinguished for their physiological and metabolomic responses. For each cultivar, 15 individuals in pots were exposed or not to 28 days of water withholding. Every 7 days, the content of sugars (including mannitol), proline, aquaporins, osmotins, and dehydrins, in leaves and stems, as well as the chemical and anatomical characteristics of the wood of the three cultivars, were analyzed. ‘Giarraffa’ reduced glucose levels and increased mannitol production, while ‘Leccino’ accumulated more proline. Both ‘Leccino’ and ‘Maurino’ increased sucrose and aquaporin levels, possibly due to their ability to remove embolisms. ‘Maurino’ and ‘Leccino’ accumulated more dehydrins and osmotins. While neither genotype nor stress affected wood chemistry, ‘Maurino’ had a higher vessel-to-xylem area ratio and a larger hydraulic diameter, which allows it to maintain a high transpiration rate but may make it more susceptible to cavitation. The results emphasized the need for an integrated approach, highlighting the importance of the relative timing and sequence of each parameter analyzed, allowing, overall, to define a “strategy” rather than a “response” to drought of each cultivar.

Enhanced Antidiabetic Effects of Gymnema sylvestre and Probiotics in Alloxan-Induced Diabetic Rats

Abstract Introduction/Objective Introduction: Gymnema sylvestre is a well-known herbal remedy for diabetes, with its anti-diabetic properties attributed to gymnemic acids isolated from its leaves. Probiotics, such as Lactobacillus acidophilus and Lactobacillus casei, have also shown potential in managing diabetes. This study aims to evaluate the combined antidiabetic effects of G. sylvestre and probiotics in alloxan-induced diabetic rats. Methods/Case Report Methods: Experimental rats were divided into seven groups: negative control, untreated diabetic control, L. acidophilus-treated, L. casei-treated, G. sylvestre-treated, a combination of L. casei and G. sylvestre-treated, and a combination of L. acidophilus and G. sylvestre-treated. Blood glucose levels, lipid profiles, and reduced glutathione levels were measured, and histopathological examination of pancreas and kidney tissues was performed. Results (if a Case Study enter NA) Results: In the third week of the experiment, the combined administration of G. sylvestre and probiotics showed the most significant reductions in glucose levels (250 mg/dL), alkaline phosphatase (ALP) (613.3 U/L), urea (31 U/L), serum creatinine (0.77 U/L), and superoxide dismutase (SOD) (854.7 UMOL). G. sylvestre alone exhibited the lowest levels of glutamate pyruvate transaminase (GPT) (30 U/L), cholesterol (41 mg/dL), triglycerides (101.3 mg/dL), very-low-density lipoprotein (VLDL) (22.9 mg/dL), and malondialdehyde (MDA) (119.3 U MOL/SEC). Probiotic treatment alone resulted in the lowest levels of uric acid (UA) (4.4 U/L) and low-density lipoprotein (LDL) (95.06 mg/dL). G. sylvestre demonstrated the highest level of high-density lipoprotein (HDL) (44 mg/dL), while probiotics exhibited the highest catalase (CAT) activity (92 UMOL/SEC). Histopathological examination revealed the preservation of normal pancreatic and renal tissue morphology with G. sylvestre treatment. Conclusion Conclusion: The combination of G. sylvestre and probiotics enhances the antidiabetic activity compared to G. sylvestre alone in alloxan-induced diabetic rats. These findings suggest a potential synergistic effect of combining herbal and probiotic therapy for diabetes management.

8638 NEGR1 is a Mediator of Exercise-Induced Neuritogenesis in Subcutaneous White Adipose Tissue, Implications for Improved Systemic Metabolism

Abstract Disclosure: P. Nigro: None. N.P. Carbone: None. T. Caputo: None. M. Vamvini: None. M.M. Columbus: None. M.F. Hirshman: None. R. Middelbeek: None. L.J. Goodyear: None. Emerging research shows that exercise training results in robust and beneficial adaptions to subcutaneous white adipose tissue (scWAT), leading to improved systemic metabolism. The mechanisms for these benefits of exercise on are not fully understood, but we have recently demonstrated that training in mouse scWAT refines nerve connections in scWAT promoting neurite outgrowth (neuritogenesis). Our multi-omics and advanced microscopy data identifies Neuronal Growth Regulator 1 (NEGR1) as a potential player in this process. Here, we determine the role of NEGR1 as a mediator of scWAT neuritogenesis and regulator of systemic metabolism. Exercise training in mice for 11 days significantly increased NEGR1 protein expression by 35% (p<0.05). Next, we directly injected NEGR1 AAV into the inguinal scWAT of untrained male mice for three weeks resulting in a 43% increase in NEGR1 protein (p<0.05). Overexpression of NEGR1 led to an increase in the innervation markers tyrosine hydroxylase (+38%, p<0.01) and synaptophysin (+39%, p<0.01), and remarkably, a 16% decrease in adipocyte cell size (p<0.05), and a 15% reduction in fasting blood glucose levels (p<0.05). This suggests that NEGR1 plays a fundamental role in regulating scWAT morphology and function, adaptations that improve systemic glucose homeostasis. To determine mechanisms for exercise training-induced increases in NEGR1 expression, we used in silico and cell culture experiments and found that NEGR1 is under the regulation of the Peroxisome Proliferator-Activated Receptor gamma (PPARg) transcription factor. Given that numerous natural and synthetic PPARg ligands are lipids, we used targeted lipidomics to identify exercise-induced lipids capable of binding and inducing PPARg expression in inguinal scWAT. We identified 13-oxo-octadecadienoic acid (13-oxo-ODE), an oxylipin derived from linoleic acid, as a potent agonist and inducer of PPARg expression. Exercise training increased 13-oxo-ODE by 3-fold (p<0.05), and 13-hydroxyoctadecadienoic acid (13-HODE), the 13-oxo-ODE precursor was also increased by 3-fold (p<0.01). To validate that 13-oxo-ODE increases NEGR1, adipocytes were incubated with 2μM of 13-oxo-ODE for 48 hours. 13-oxo-ODE increased NEGR1 expression by 27-fold (p<0.0001) and NEGR1 protein by 2-fold (p<0.01). In summary, NEGR1 is a novel exercise-induced molecule that regulates neuronal refinement in scWAT. Our data also suggest that the synthesis of 13-oxo-ODE leads to PPARγ activation that in turn promotes NEGR1 expression in scWAT. NEGR1 has beneficial effects on scWAT that are associated with improved systemic metabolism, making NEGR1 a novel target for treatment of obesity and cardiometabolic diseases. Presentation: 6/1/2024

Exploring the Dual Benefits of Fermented and Non-Fermented Garlic Powder on Growth, Antioxidative Capacity, Immune Responses, and Histology in Gray Mullet (Liza ramada)

This study investigated the effects of dietary garlic powder and fermented garlic powder supplementation at 1% and 2% levels on growth performance, digestive tract efficacy, blood biochemistry, immunity, and antioxidant status of Liza ramada (n = 225 fish; 86.00 ± 0.42 g) over a 60-day period. Fish fed diets supplemented with both forms of garlic at both levels exhibited significantly improved final body weight, weight gain, specific growth rate, and feed conversion ratio compared to the control group. Digestive enzyme activities (amylase, lipase, and protease) were significantly enhanced in all supplemented groups. Blood biochemical analysis revealed reduced glucose levels and increased total protein in garlic-supplemented groups, with no adverse effects on liver or kidney function markers. Immune parameters, including lysozyme activity, bactericidal activity against Streptococcus agalactiae, alternative complement pathway (ACP), and respiratory burst (NBT), were significantly enhanced in garlic-supplemented groups, with fermented garlic showing more pronounced effects. Antioxidant enzyme activities (SOD, CAT, and GPx) were also significantly increased in all supplemented groups, particularly in those fed fermented garlic. No significant differences in survival rates were observed among treatments. The results suggest that both garlic powder and fermented garlic powder supplementation, especially at the 2% level, can effectively improve growth, feed utilization, immune function, and antioxidant status in L. ramada. Fermented garlic generally demonstrated superior effects, indicating its potential as a beneficial feed additive in aquaculture. Based on these findings, it is recommended to incorporate fermented garlic powder at a 2% level in L. ramada diets to optimize growth performance and health status. Further research is warranted to investigate the long-term effects and cost-effectiveness of this supplementation strategy in commercial aquaculture settings.

A-079 Investigation of gut microbial flavonoid catabolites in metabolic diseases

Abstract Background Flavonoids, a secondary metabolite found in plant-based diets, have gained attention in the last decade for their antioxidative properties in high-fat diet induced obesity animal models and human studies. Previous work showed that certain gut microbiota members can metabolize flavonoids into monophenolic acids (MPAs), and some of these MPAs have similar effects to insulin when administered orally. Our objective is to explore the microbiome connection between flavonoid-rich diets and improved metabolic parameters in obesity. We hypothesize that flavonoid-supplemented diets are most effective in the presence of gut microbiota capable of MPA formation and that these bacterial metabolites are the main bioactive compounds responsible for the improved metabolic parameters Methods To investigate our hypothesis, we fed male and female C57BL/6 mice a high-fat control diet (HFD) or the same diet supplemented with 1% MPA or 1% berry extract for 12 weeks. Each group was further divided into subgroups that received regular drinking water (RW) or antibiotic water (ABW) to suppress gut microbial communities. A range of metabolic parameters, such as body weight, lean and fat mass, glucose and insulin tolerance, histological assessment of liver cells, quantification of liver injury biomarkers, transcriptional changes in metabolically active tissues, and glucose and lipid metabolism pathways, were monitored. Additionally, 16s sequencing was performed on the cecal microbial composition of each group. Results Mice on HFD control with RW or ABW showed prominent hepatic steatosis and an increase in liver lipids accumulation demonstrated by a significant decrease in the activation of lipid metabolism pathways. Similarly, mice on HFD with 1% MPA and RW or ABW exhibited a significant reduction in hepatic steatosis and an increase in the activation of the lipid metabolism pathways, regardless of gut microbiota presence. In line with our hypothesis, mice on HFD with 1% berry extract and RW showed a similar reduction in hepatic steatosis to both 1% MPA groups. However, mice on HFD with 1% berry extract and ABW displayed noticeable hepatic steatosis, indicating the loss of the positive effect provided by berry extract metabolites once gut microbiota was depleted by antibiotics. Insulin tolerance test revealed a gut microbial effect as well in the HFD with 1% berry extract, illustrated by a significant reduction in glucose levels after insulin injection and an increase in insulin sensitivity. In contrast, the HFD control mice experienced an increase in glucose levels after insulin injection and insulin resistance. Although there were notable decreases in fasting blood glucose, there were no significant effects on fat and lean mass, insulin, glucagon, or liver injury marker levels. Finally, the mice on HFD with 1% berry extract had significantly more diverse cecal microbial communities than those fed HFD or HFD with 1% MPA. Conclusions Feeding mice a flavonoid-rich diet in the presence of intact gut microbiome can improve metabolic parameters associated with metabolic diseases, potentially preventing, or reversing these diseases. Our findings suggest promising avenues for treatment, such as dietary flavonoid supplementation with concurrent gut microbial probiotic therapy.

The Effect of COVID-19 Lockdown Among Adolescents with Type 1 Diabetes: A Systematic Review and Meta-Analysis.

The aim of this study was to assess how the lockdown of the COVID-19 pandemic had affected the glycaemic control of adolescents aged 10-19 with type 1 diabetes. A comprehensive search of literature was performed in PubMed, Scopus, Web of Science, and ProQuest. Published articles up to September 2022 were included. The Glucose Monitoring Index (GMI) and HbA1c level were defined as outcome variables. Average glucose level was found to be a common variable in both HbA1c levels and GMI; therefore, HbA1c and GMI were converted to average glucose (mg/dL) using appropriate formulas. Studies reported the outcomes in two or three periods (pre-lockdown, lockdown, and post-lockdown) were included in the analysis. A paired wise meta-analysis was performed among the studies that reported all three periods. Homogeneity across studies was assessed using I2 statistic. Fourteen studies were included in the study. The pooled average glucose during the lockdown decreased to 166.9 mg/dL (95% CI, 153.78, 180.02) from 205.793 mg/dL (95% CI, 188.412, 223.173) during the pre-lockdown period, then it increased to 204.23 mg/dL (95% CI, 186.17, 222.29) during the post-lockdown period. A paired wise meta-analysis indicated a reduction in average glucose levels. However, it was not statistically significant, possibly due to the small number of studies that reported data from all three periods. Although the descriptive analysis of our study showed that the lockdown had affected (decreased) the average glucose level among adolescents with type 1 diabetes, this was not statistically significant in the pooled analysis.

Identification of compounds from Origanum compactum and Origanum elongatum using HPLC/UV-ESI-MS and comparative analysis of their antioxidant, antimicrobial, anticoagulant, and antidiabetic properties

The aim was to assess the phytochemical composition, phenolic component levels, and biological properties of the flowering tops of Origanum compactum and Origanum elongatum. The study employed phytochemical assays, spectrophotometric techniques for quantitative analysis of polyphenols, flavonoids, and tannins, and compound identification using HPLC/UV-ESI-MS. The antimicrobial, antioxidant, anticoagulant, and antidiabetic properties were examined both in vitro and in vivo. The results showed that the O. compactum extract had significantly high levels of total polyphenols, measuring 47.368 mg gallic acid equivalents per gram, and flavonoids, measuring 14.839 mg quercetin equivalents per gram. The phytochemical examination of O. compactum revealed that lithospermic acid accounted for 36.82 % of the chemicals detected, followed by salvianolic acid C at 12.57 % and ros-marinic acid at 6.01 %. The main constituents of O. elongatum are salvianolic acid C (14.46 %), luteolin-3-O-glucuronide (13.51 %), salvianolic acid B (12.24 %), rosmarinic acid (7.83 %), and rutin (6.18 %). The results demonstrated different levels of effectiveness against the investigated microorganisms, with the extract from O. compactum exhibiting better activity, particularly against Gram-negative bacteria, certain yeasts, and the fungus Aspergillus niger. The aqueous extracts of both Origanum species demonstrate significant antioxidant activity. O. compactum has a higher total antioxidant capacity (IC50 of 35.083 μg/mL) compared to O. elongatum (IC50 of 77.080 μg/mL). However, O. elongatum has a higher reducing power (35.697 μg/mL) compared to O. compactum (42.563 μg/mL). In vivo evaluations revealed that the aqueous extracts of O. compactum and O. elongatum possess significant antihyperglycemic and anticoagulant properties. The extracts demonstrated a marked reduction in blood glucose levels during the oral glucose tolerance test (OGTT) in Wistar rats and effectively prolonged both prothrombin time (PT) and activated partial thromboplastin time (aPTT), highlighting their ability to inhibit coagulation pathways. Moreover, their comparable efficacy to standard antihyperglycemic medications and absence of severe toxicity, even at high doses, underscore their therapeutic potential for safe and effective treatment applications. Between the two species, O. compactum exhibited superior efficacy in key biological activities such as antioxidant, antimicrobial, and anticoagulant properties, making it a strong candidate for therapeutic applications. This study underscores the value of Origanum species as a rich source of bioactive compounds, offering significant potential in pharmaceuticals, nutraceuticals, and agri-food industries. The findings pave the way for further exploration of their diverse applications.

Hypoglycemic activity of Garcinia mangostana L. extracts on diabetes rodent models: A systematic review and network meta-analysis.

Diabetes mellitus is a significant global health issue, and alternative treatments from natural products like Garcinia mangostana L. [Clusiaceae] or GM are being explored for their potential benefits. This study focused on evaluating the hypoglycemic effects of GM on diabetic rodent models. A comprehensive search was conducted in PubMed, Scopus, and Embase for studies reporting blood glucose levels within 2weeks as the primary outcome and changes in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) as secondary outcomes. A network meta-analysis (NMA) was performed to determine the pooled effectiveness of each intervention, estimating the weighted mean difference (WMD) and 95% confidence interval (CI) from both direct and indirect evidence. The surface under the cumulative ranking curve (SURCA) was used to rank the interventions. Ten articles were identified, with nine included for quantitative analysis. All GM extracts showed greater effectiveness than the control in decreasing blood glucose levels within 2weeks. GM at 200mg/kg (GM200) was the top-ranked extract for reducing glucose levels beyond 2weeks and increasing HDL-C levels. The ethanol extract of GM at 200mg/kg (GME200) was the most effective for blood glucose reduction within 2weeks and for TC and TG reductions. The methanol extract of GM at 200mg/kg (GMM200) was the top-ranked extract for LDL-C reductions. GM and its extracts demonstrated significant hypoglycemic activity and improvements in lipid profiles in diabetic rodent models, highlighting their potential as therapeutic agents for the prevention and treatment of diabetes mellitus. Further research in human trials is warranted to confirm these findings and establish clinical applications. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023426254.

Exercise intensities and metabolic health: Targeting blood glucose, insulin, and C-peptide levels in adults with prediabetes in the postprandial state

ObjectiveExercise improves postprandial glycemia and insulin sensitivity in individuals with prediabetes, but the optimal intensity for this metabolic regulation remains unclear. The current study explored the impact of various exercise intensities on blood glucose, insulin, and C-peptide levels in prediabetic individuals to identify the optimal intensity for improving these metabolic indicators. MethodsIn this crossover study, 25 individuals with prediabetes participated in exercise sessions at four different intensities 50 %, 60 %, 70 %, and 80 % of their predicted maximum heart rate using a treadmill. Each session lasted 30 min, including a 5-min warm-up and 5-min cool-down period. Blood samples were collected at four time points: during fasting, immediately before exercise, and 30 and 60 min post-exercise. These samples were analyzed for glucose, insulin, and C-peptide levels. The effects of exercise intensity on these parameters were evaluated using repeated measures analysis of variance (ANOVA), with post hoc tests conducted to determine specific differences between the intensities. ResultsThe participants had an average age of 34.88 years, mean height of 170 cm, and body mass index of 30.34 kg/m2. A significant reduction in insulin and glucose levels post-exercise was observed at 70 % intensity (p ≤ 0.001). Despite high fasting blood glucose levels (110–115 mg/dL), significant reductions were noted at 30 and 60 min post-exercise (p ≤ 0.001). Insulin levels approached near baseline at 70 % intensity, from fasting (26.74 ± 20.83) to 60 min post-exercise (28.47 ± 20.79), indicating a positive response at this intensity. C-peptide levels also showed significant changes, with 70 % intensity exercise bringing them closest to fasting levels by 60 min post-exercise. ConclusionThis study highlights the importance of exercise intensities in enhancing metabolic parameters in individuals with prediabetes. Specifically, 70 % of the predicted maximum heart rate was beneficial, optimizing insulin sensitivity and potentially reducing the risk of progressing from prediabetes to diabetes.

Biochemical characterization of green zinc nanoparticles fabricated by Stevia rebaudiana aqueous extract and its nephroprotective effects against streptozotocin-induced nephropathy in mice: A histopathological study

The development and creation of novel therapeutic supplements and medications with exceptional efficacy in treating nephropathy is a top priority for both developed and developing nations. The antioxidant, nephroprotective, and cytotoxicity effects of green synthesized zinc nanoparticles (ZnNPs) containing Stevia rebaudiana aqueous extract were assessed in this study. The combination of Stevia rebaudiana aqueous extract with Zn nitrate solution resulted in the Zn nanoparticles production. The characteristics of Zn nanoparticles were determined using transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray crystallography (XRD), ultraviolet–visible spectroscopy (UV–Vis) and field emission scanning electron microscopy (FESEM). The synthesized nanoparticles typically ranged in size from 20 to 30 nm. These nanoparticles displayed a crystalline structure and maintained a uniform shape. To induce diabetes, 60 mg/kg of streptozotocin was administered intraperitoneally in 50 mice (n = 10). The treatment groups received glibenclamide (0.5 mg/kg) and 100 and 200 μg/kg of Zn nanoparticles through gavage for 25 days. Additionally, there was a positive control group for comparison (treated-diabetic). On the final day, serum levels of creatinine, urea, and blood glucose were determined in the samples. Following tissue processing, 5 μm sections of kidneys were stained with periodic acid Schiff (PAS) for subsequent stereological and histopathological analysis. The groups treated with ZnNPs exhibited a notable reduction (p < 0.05) in urea and blood glucose levels (about 190 mg/dL) when compared to the diabetic group (about 500 mg/dL) that did not receive treatment. Furthermore, the treatment with a high dose of ZnNPs resulted in a significant decrease (p < 0.05) in kidney weight and volume (including vessels, interstitial tissues, collecting ducts, loop of Henle, and distal and proximal tubules), and kidney structures length (including vessels, collecting ducts, loop of Henle, and distal and proximal tubules) (p > 0.05). Based on the findings, ZnNPs can control urea and blood glucose levels while preventing kidney damage in streptozotocin-induced diabetic animals. This research proposes utilizing zinc nanoparticles synthesized from Stevia rebaudiana as a supplementary treatment for diabetes and kidney protection in developing nations.

Colonic targeting insulin-loaded trimethyl chitosan nanoparticles coated pectin for oral delivery: In vitro and In vivo studies

Colon-targeted delivery offers several benefits for oral protein delivery, such as low proteolytic enzyme activity, natural pH, and extended residence time, which improve the bioavailability of the encapsulated protein. Therefore, we hypothesize that developing a novel colonic nanocarrier system based on modified chitosan, which enhances solubility at natural pH and is coated with a colon-degradable polymer, will provide an effective delivery system for oral insulin. This study aims to synthesize insulin-loaded pectin-trimethyl chitosan nanoparticles (Ins-P-TMC-NPs) as an oral insulin delivery system and evaluate their efficacy both in vitro and in streptozotocin-induced diabetic male rats. N-trimethyl chitosan (TMC), synthesized via a methylation method, was used to prepare insulin-TMC nanoparticles coated with pectin via the ionic gelation method. The nanoparticles were characterized for their physicochemical properties, cumulative release profile, and surface morphology. In vitro biological cytotoxicity and cellular uptake of the nanoparticles were evaluated against HT-29 cells using an MTT assay and fluorescent microscopy, respectively. The in vivo blood glucose-lowering effect was assessed in diabetic male Sprague–Dawley rats, with in vivo toxicity evaluated in the liver, spleen, duodenum, pancreas, and kidney through histological studies (H&E staining). The results showed that Ins-P-TMC-NPs were spherical, with an average size of 379.40 ± 40.26 nm, a polydispersity index of 24.10 ± 1.03 %, a zeta potential of +17.20 ± 0.52 mV, and a loading efficiency of 83.21 ± 1.23 %. Compared to uncoated TMC nanoparticles, Ins-P-TMC-NPs reduced insulin loss in simulated gastrointestinal fluid by approximately 67.23 ± 0.97 % and provided controlled insulin release in simulated colonic fluid. In vitro bioactivity studies revealed that Ins-P-TMC-NPs were non-toxic, with cell viability of 91.12 ± 0.91 %, and exhibited high cellular uptake in the HT-29 cell line with a fluorescence intensity of 37.80 ± 2.40. Furthermore, in vivo studies demonstrated a sustained reduction in blood glucose levels after oral administration, peaking after 8 h with a glucose reduction of 87 ± 1.03 %. Histological sections showed no signs of toxicity. Overall, the developed colon-targeted oral insulin delivery system shows great potential as a candidate for oral insulin administration.

Evaluation of the Hypoglycemic and Hypolipidemic Potential of Extract Fraction of Quercus baloot Griff Seeds in Alloxan-induced Diabetic Mice.

The discovery and development of new phytomedicines can be greatly aided by plants because of their tremendous therapeutic benefits, efficiency, cost-effectiveness, lack of side effects, and cheaper therapies. In this regard, Quercus baloot, generally known as oak, is used in folkloric medicine for treating and preventing various human disorders, including diabetes. For this purpose, the present study aimed to evaluate crude methanolic extract and various fractions of Quercus baloot for antihyperlipidemic and antihyperglycemic potential followed by the analysis of active compounds. The hypoglycemic and hypolipidemic activity was evaluated in Swiss male Albino mice by administering an oral dose of 150-300 mg/kg of Q. baloot extracts in alloxan induced diabetic mice for 14 days. The results revealed that crude methanolic extract at a dose of 300 mg/kg exhibited a significant reduction in the blood glucose level (198.50 ± 1.99 mg/dl) at day 14 and the same treatment significantly increased the body weight (31.26 ± 0.27 g) at day 14 in comparison to the control group. Moreover, the biochemical parameters were investigated which presented an increase in high-density lipids (HDL) (30.33 ± 0.33 mg/dl), whereas low-density lipids (LDL) showed a significant decrease (105.66 ± 0.26 mg/dl). Additionally, triglyceride levels 104.83 ± 0.70 mg/dl, and total cholesterol 185.50 ± 0.76 mg/dl are significantly decreased. In serum biochemical analysis creatinine and hepatic enzyme markers, like serum glutamate pyruvate transaminase (32.00 ± 0.36 U/mg), serum glutamate oxaloacetate transaminase (34.33 ± 0.61 U/mg), and alkaline phosphatase (157.00 ± 0.73 U/mg), were significantly reduced by the crude methanolic extract at a dose of 300 mg/kg as compared to the control group. The antioxidant enzymes like Superoxide dismutase (4.57 ± 0.011), peroxidases dismutase (6.53 ± 0.014, and catalase (8.38 ± 0.014) at a dosage of 300 mg/kg of methanolic extract exhibited a significant increase. The histopathological study of the diabetic heart, liver, and pancreas showed substantial restoration of damaged tissues in the methanolic extract 150 and 300 mg/kg treated group, which supports the effectiveness of Q. baloot seeds. The gas chromatography-mass spectrometry analysis of methanolic extract identified 10 antidiabetic active compounds in the Q. baloot seeds, validating the antihyperglycemic activity. Thus, methanolic crude extract at the doses 150 and 300 mg/kg of Q. baloot showed significant antihyperlipidemic and antihyperglycemic activities, which validate the folkloric utilization of Q. baloot as a remedy in diabetes. In conclusion, the 300 mg/kg methanolic extract of Q. baloot has notable hypoglycemic and hypolipidemic potential, supporting the plant's traditional medicinal usage in the treatment of diabetes and its complications. Further studies are needed for the purification, characterization, and structural clarification of bioactive compounds.

Cardiorenal Benefit of Tirzepatide in Type 1 Diabetes: A Case Report

Abstract Patients with type 1 diabetes (T1D) who are obese are at risk of cardiovascular disease, renal diseases, and other complications. Unfortunately, there is currently no cure for T1D, necessitating individuals with this condition to rely on lifelong insulin therapy. Tirzepatide, a dual-acting glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist, has recently been approved for treating type 2 diabetes. We report the case of a 38-year-old male who presented with T1D, stage 2 chronic kidney disease, obesity, and other comorbidities. He was prescribed tirzepatide 2.5 mg initially, followed by titration up to 5 mg. A significant reduction in blood glucose levels, weight, and microalbumin levels was observed. Additionally, the systolic blood pressure level was also seen to improve. These results highlight new indications of tirzepatide in managing T1D and obesity. However, further studies are warranted to explore its efficacy and safety in patients with T1D.

Evaluation of a mucoadhesive auto-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration

This study investigated the potential of self-nanoemulsifying drug delivery systems (SNEDDS) to optimize the oral bioavailability of insulin. Insulin complexes with phospholipids and enzymatically-modified phospholipids were developed and incorporated into the SNEDDS using Lauroglycol FCC as the oily phase and Cremophor EL and Labrafil M1944CS as the surfactant and co-surfactant, respectively. Additionally, mucoadhesive polysaccharides (sodium alginate and guar gum) were added further to enhance the bioavailability of insulin in these systems. The objective was to increase the bioavailability and bioactivity of an insulin-modified phosphatidylcholine complex by incorporating mucoadhesives into the SNEDDS. After polymer inclusion, the resulting nanoemulsions exhibited droplet diameters ranging from 57 to 83 nm. Cytotoxicity and apparent permeability tests were conducted on Caco-2 and NIH 3 T3 cell lines, revealing that toxicity was related to the concentrations of insulin and surfactant in the nanosystems—formulations containing guar gum as a mucoadhesive showed better tolerance to cell death in the Caco-2 line. In a murine diabetes model, the SNEDDS were observed to reduce glucose levels by up to 61.63 %, with a relative bioavailability of 2.25 % compared to subcutaneously administered insulin. These results suggest that SNEDDS incorporating mucoadhesives could represent a promising strategy for improving oral insulin delivery.