Glucose Stress Research Articles

Effect of aqueous extract of Mondia whitei fruits on high sucrose-induced oxidative stress in Drosophila melanogaster

Background/Aim: High sugar intake plays an important role in oxidative stress, which has been linked to development of diseases like diabetes. In this study, the effect of aqueous extract of Mondia whitei (AEMW) fruits on high sucrose-induced oxidative stress in Drosophila melanogaster was investigated. Materials and Methods: Adult flies (1 – 3 days old) were exposed to graded doses of AEMW for 12 days to determine the safe dose. Based on this, new flies were grouped into 5 (n = 5; 40 flies per vial). Group 1 served as control and were fed with basal diet, and group 2 with basal diet containing 30% sucrose. Groups 3 and 4, in addition to diet containing 30 % sucrose, were exposed to 0.25 and 0.5 mg AEMW/g diet, respectively, and group 5 flies were exposed to diet containing 0.5 mg AEMW/g diet only. Treatment lasted for 7 days. Biochemical assays such as glucose level, markers of antioxidant and oxidative stress were carried out to assess the effect of high sucrose and/or AEMW on flies. Results: Doses of AEMW up to 0.5 mg/g diet was safe for the flies. High sucrose diet significantly (p < 0.05) increased the level of glucose and oxidative stress markers, and reduced the levels of antioxidant parameters when compared to the control. These changes were prevented by the doses of AEMW. Conclusion: It can be concluded that AEMW possesses anti-hyperglycemic and antioxidant properties, and could be suggested to act against oxidative stress induced by high sucrose in fruit flies.

Exploration and comparison of stress hyperglycemia-related indicators to predict clinical outcomes in patients with spontaneous intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a prevalent hemorrhagic stroke characterized by a significant fatality rate and severe neurological impairments. Stress hyperglycemia has been confirmed to have a significant prognostic role in a range of diseases. However, studies on the association between stress hyperglycemia and the outcome of ICH have not currently been reported. Critically ill patients diagnosed with ICH in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were included in our study. Logistic regression and Cox regression were used to analyze the correlation between stress hyperglycemia and the outcome of ICH. The predictive ability of different glucose metrics was demonstrated by the receiver-operating characteristic (ROC) curve and was further compared by the integrated discrimination improvement (IDI) index. A total of 880 ICH patients in the MIMIC-IV database were included in this study. In logistic regression and Cox regression, blood glucose level (BGL), glycemic gap (GG), and stress hyperglycemia ratio (SHR) were independent predictors of unfavorable outcomes in ICH after adjustment for other confounders. The IDI results indicated that the 5-day maximum stress hyperglycemia ratio had better predictive performance than glycemic gap and blood glucose level in-hospital mortality and 1-year mortality, and the predictive performance of the 5-day maximum stress hyperglycemia ratio was better than that of stress hyperglycemia ratio measured at admission. In the age-stratified subgroup analysis, the 5-day maximum stress hyperglycemia ratio was more sensitive in predicting long-term outcomes in the young subgroup than in the elderly subgroup. The 5-day maximum stress hyperglycemia ratio is strongly correlated with an elevated risk of mortality in ICH patients and displays a better predictive ability than glycemic gap and blood glucose level in the short/long-term prognosis of ICH.

Abstract 4140181: Mechanisms of SGLT-2 Inhibitor Empagliflozin in Attenuating Intramitochondrial Stress and Restoring Mitochondrial Function in Hyperglycemic Cardiomyocyte

Systemic hyperglycemia causes tissue damage and triggers cardiovascular disease (CVD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a novel class of glucose-lowering agents that have shown unexpected benefits in clinical trials for the treatment of CVDs. We aim to investigate the underlying mechanisms of how SGLT-2 inhibitors alleviate CVDs associated with elevated glucose stress. iPSC-derived cardiomyocytes (iPSC-CM) were incubated with high glucose concentrations for 72 hours. Mitochondrial function in these cardiomyocytes was assessed by flow cytometry with JC-1 staining and ATP luminescence assay. Intracellular reactive oxygen species (ROS) and intramitochondrial calcium stress were measured using CellROX, MitoSOX, and Rhod-2 AM staining. Patch clamp was employed to determine ion current changes in the cardiomyocytes. Mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were determined using the Seahorse XFe96 analyzer. In addition, qPCR, Western blot, and DM mouse heart histological analysis were performed to assess the regulation of associated molecules. The results indicated that exposure to a high glucose environment caused cardiomyocyte injury and impaired mitochondrial biosynthesis. Empagliflozin exhibited a beneficial effect on mitochondrial function by reducing ROS production and calcium deposition. It also mitigated the reduction in respiratory OCR of cardiomyocytes induced by high glucose incubation. Furthermore, molecular analysis revealed that Empagliflozin attenuated the dysregulation of mitochondrial calcium channels and biosynthesis by reducing associated gene expression, including Bcl2 , Mfn1 , Mx2 , Oas1 , Ant3 , Mcu , Micu1 , Vdac1 , Ryr2 , and Cypd-ppid . Histological analysis of DM mouse hearts demonstrated that reduced MFN2 and ZBP1 were target molecules for hyperglycemia-induced reduction of calcium channel currents in cardiomyocytes and could be restored by Empagliflozin treatment. This study concludes that high glucose stress diminishes mitochondrial calcium channel regulators MFN2 and ZBP1 in cardiomyocyte, which reduces calcium channel currents and leads to sensitization of cardiomyocyte to arrhythmogenesis, resulting in VT/VF. It provides experimental evidence for the clinical efficacy of Empagliflozin in ameliorating CVDs and managing diabetes-related CVDs.

Abstract 4125587: Vasomotor function and its regulation by perivascular adipose tissue in metabolic syndrome vary depending on severity and combination of metabolic parameters

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates arterial tone by releasing vasorelaxing/vasocontracting factors, the effects of PVAT on vasomotor function have been heterogeneously reported. Various PVAT functions can result from the severity or combination of metabolic parameters in MetS. Therefore, we compared the effects of mesenteric arterial PVAT on the nitric oxide-dependent vasorelaxation response among the three metabolic syndrome (MetS) model strains. We compared male OLETF, Zucker fatty (ZF), and SHRSPZF (SPZF) rats aged 20 weeks to lean controls, LETO, ZF +/+ , and Wistar-Kyoto (WKY) rats. To determine the effects of PVAT on vasodilators, we used organ bath techniques to assay nitroprusside-induced relaxation of isolated mesenteric arterial ring preparations with intact or removed PVAT. The waist circumference to length ratio in OLETF and ZF rats was higher than that in SPZF rats, and the systolic blood pressure was higher in SPZF rats than in the other groups. In the serum, there was no significant difference in triglyceride levels. Still, glucose and thiobarbituric acid reactive substance levels were higher in OLETF and SPZF rats than in ZF rats. Relaxation in ZF rats did not change compared to that in ZF +/+ rats and the presence of PVAT. In contrast, relaxation in OLETF rats was lower than in LETO rats, and there was no difference between the presence and absence of PVAT. However, relaxation in SPZF rats was lower than in WKY rats, and relaxation increased to the same level as in WKY rats in the presence of PVAT. This study unveils novel insights, suggesting that high serum glucose and oxidative stress cause arterial dysfunction, whereas high blood pressure induces PVAT functional changes. These findings underscore the complex interplay between metabolic disorders and vascular health, potentially paving the way for more targeted interventions in patients with MetS.

Improving diabetic wound healing: The therapeutic potential of allulose supplement in diabetic skin tissue repair and inflammation modulation

The increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide presents significant challenges in the management of impaired tissue repair in diabetic skin wounds, which has emerged as a critical health concern. Addressing this issue while minimizing adverse effects remains crucial. Allulose has been shown to exhibit hypolipidemic and anti-inflammatory properties, alleviating obesity and atherosclerosis by improving insulin resistance and impaired glucose tolerance. However, its underlying effects and mechanisms in repairing diabetic skin damage remain poorly understood. In this study, we demonstrated that oral administration of allulose remarkably ameliorated T2DM-compromised skin tissue wound associated with the stimulation of skin granulation, surrounding tissue formation, and activated fibroblasts, under high-fat diet (HFD) feeding condition. In addition, administration partially promoted collagen deposition, reduced M1 macrophage polarization, facilitated neovascularization, and mitigated tissue inflammation in the T2DM rats upon HFD feeding. Moreover, allulose could significantly alleviate high glucose stress condition-induced inflammatory response, correlative with modulation of p38/NLRP3/Caspase-1 signaling. In addition, allulose could also ameliorate high glucose stress-compromised cell viability and proliferative capacity, related to stimulation of mTOR pathway in part. Taken together, our study revealed that T2DM compromised some certain factors which are crucial for skin tissue healing and wound repair upon HFD condition. The work highlighted the potential beneficial effects of orally administered allulose for healing diabetic skin wounds and supported a novel strategy for managing diabetes patients adjunctively with allulose dietary supplement.

Unraveling the mechanism of Ligilactobacillus salivariusAR612 in response to glucose stress from the insights of genome and transcriptome analysis

Unraveling the mechanism of <em>Ligilactobacillus salivarius</em>AR612 in response to glucose stress from the insights of genome and transcriptome analysis

Ambrisentan reverses the prosenescent and anti-autophagic effect of high glucose on human pulmonary artery endothelial cells exposed to hypoxia

Abstract Background Cardiovascular (CV) comorbidities (systemic hypertension, hyperlipidemia, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease) are associated with reduced treatment response to specific drugs for group 1 pulmonary arterial hypertension (PAH). Often this epidemiological evidence is the result of misdiagnosis of group 2 PH associated with left heart disease, but it can also be explained as the intrinsic loss of the ability of pulmonary endothelial cells to respond to specific antiremodeling drugs. Aims To evaluate the impact of high glucose and hyperosmolar stress on the responsiveness of human pulmonary artery endothelial cells (hPAECs) to the endothelin receptor antagonist ambrisentan in terms of senescence, autophagic activity, viability and expression of some microRNAs involved in pulmonary arterial remodeling. Methods We incubated hPAECs with high glucose (HG, 30.5 mM) or high mannitol (HM, 25 mM), with/without ambrisentan (0.02 nM) in normoxia (N) or hypoxia (H) for 24 h and tested them for cell viability (MTT assay), protein and miRNA levels, autophagy and senescence (β-Gal assay) in vitro. Results H induced cell death as compared to N (752 ± 44 vs 701 ± 45 Abs units, p = 0.03). H reduced autophagy (Figure 1A-C) and induced senescence (Figure 1D), an effect further potentiated by HG and HM. Treatment with A in N and H significantly reversed the effect of HG but not HM on autophagy (Figure 1A-C) and senescence (Figure 1D). H increased the abundance of antiapoptotic miR124-3, compared to N in vehicle (V)-treated hPAEC (p=0.008) (Figure 2A), and induced a similar effect on antiapoptotic and proliferative miR191-3p, although not statistically significant (Figure 2B). In N, A potentiated the expression of both miR124-3p (p=0.007) and miR191-3p (p=0.02) in HG-treated hPAEC, and only miR191-3p in HM-treated hPAEC (p=0.01). A induced a similar effect on miR191-3p in hPAEC exposed to H+HG (p=0.02), with a non-statistically significant trend on miR124-3p. Conclusions In hPAEC exposed to H, A retains its pro-autophagic and antisenescent effects in an in vitro model mimicking diabetes. miR124-3p and miR191-3p may act as biomarkers of disease and treatment response to specific drugs in patients with PAH.Figure 1:autophagy and senescenceFigure 2:miRNA expression

Effectiveness of psychoeducation interventions for pregnant women with gestational diabetes mellitus: an integrative review

BackgroundGestational diabetes mellitus occurs in approximately 15–17% of pregnant women worldwide and causes high mortality and morbidity for mothers and infants. Pregnant women who are newly diagnosed with gestational diabetes mellitus experience higher levels of stress and anxiety than pregnant women without this condition. Thus, it is important to identify effective interventions to help pregnant women cope with the additional stress and anxiety associated with pregnancy-related complications.AimThis integrative review aimed to synthesise evidence on the effects of educational interventions for pregnant women with gestational diabetes mellitus regarding knowledge, self-efficacy, self-care behaviour, anxiety, depression, and birth outcomes.MethodsAn integrative review of articles published between 2009 and 2024, written in English and Arabic. The review followed the Whittemore and Knafl’s 5-stage process framework.ResultsFrom the 922 abstracts identified using search terms, 16 articles were eligible for this review. Psychoeducational interventions were provided for (1) informational support: information about gestational diabetes mellitus, diabetes mellitus, blood glucose monitoring, exercise management, diet management, and stress; (2) motivational support: setting individual goals, enhancing health behaviours, and motivational messages; (3) emotional support: expression of feelings, enforcement of self-management, and sharing of experiences; and (4) relaxation techniques: breathing exercises, meditation, and mindfulness. In this review, only two studies entirely focused on reducing stress and anxiety through cognitive-behavioural stress management training and mindfulness training. The effects of the interventions on self-efficacy, knowledge, depression, anxiety, and birthing outcomes were inconsistent due to variations in intervention designs and duration. However, consistent positive outcomes were found in self-care behaviours.ConclusionThis integrative review found informational and motivational support were frequently used by pregnant women. In contrast, emotional support and relaxation techniques were rarely used. Psychoeducational interventions may enhance self-care behaviours, improve self-efficacy, and reduce stress and depression for women with gestational diabetes mellitus. Nurses and midwives play an essential role in providing holistic care through comprehensive psychoeducational interventions for pregnant women.

ARID1A recruits GATA2 to regulate the senescence of trophoblast cells under high-glucose condition

IntroductionGestational diabetes mellitus (GDM) is a common complication during pregnancy. The hyperglycemic stimulation of gestational diabetes inhibits the invasion of the placental trophoblast cells. Some studies have indicated that the senescence of trophoblast cells weakens their invasive capacity, while the mechanism of trophoblast cells senescence in GDM remain elusive. MethodsWe performed western blotting and Immunohistochemical staining to investigate AT-Rich Interaction Domain 1A (ARID1A) expression in GDM placental tissues. 5 mM and 30 mM glucose treated HTR-8/SVneo cells to simulate normal glucose (NG) stress and high glucose (HG) stress. Cell proliferation capacity was investigated by CCK8 assay and cell cycle assay. SA-β-gal was used to detect cellular senescence. Chip-seq characterized the binding site of ARID1A to CDKN1A. In conjunction with bioinformatics analysis, co-immunoprecipitation assays, Chip-qPCR and luciferase reporter assays were performed to prove ARID1A recruits GATA2 to CDKN1A. ResultsWe found that ARID1A has a higher expression levels in GDM placental tissues compared to the control. ARID1A overexpression suppressed cell proliferation, induced cell cycle arrest and promoted cell senescence. Conversely the inhibition of ARID1A significantly rescues HG induced senescence of trophoblast cells. To further characterize the mechanism by which ARID1A regulate the transcription of CDKN1A, co-immunoprecipitation assays, Chip-qPCR and luciferase reporter assay indicate that ARID1A recruits GATA2 to regulate the transcriptional activity of CDKN1A. DiscussionOur study uncovers a ARID1A mediated regulatory mechanism in GDM trophoblast cell senescence and suggests that targeting the placental ARID1A might provide new diagnostic and therapeutic strategies for GDM.

7725 Could COVID-19 Be the Trigger for Type 1 Diabetes?

Abstract Disclosure: E. Ahsan: None. F.F. Foo: None. A. Ravin: None. M. Akula: None. K. Hu: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. Introduction: COVID-19 disrupts glucose homeostasis, which may result in hyperglycemia and new-onset diabetes mellitus. It has been hypothesized to be caused by an increased inflammatory response, increased insulin resistance, and a degree of acute viral pancreatic damage. A meta-analysis showed that the incidence of new-onset diabetes was found to be as high as 14.4% (95% CI: [5.9%-25.8%]). Here, we report a case of COVID-19-induced diabetes to spread awareness among healthcare providers and encourage early detection to prevent long-term complications. Clinical Case: A 54-year-old African American female with a past medical history of hyperlipidemia, obesity, and hypothyroidism presented to our endocrinology office for evaluation and management of diabetes mellitus (DM). She presented with symptoms of 66-pound weight loss, polydipsia, polyphagia, and polyuria. Her labs on diagnosis were significant for blood glucose of 550 mg/dl (70-100 mg/dl), hemoglobin A1c &amp;gt;15.5% (&amp;lt;5.7%), and bicarbonate 23 mmol/L (20-31 mmol/L). She started on insulin and then switched to semaglutide after six months. Her fasting glucose on the follow-up visit was 103 mg/dl, the anti-glutamic acid decarboxylase 65 (GAD-65) antibody was 8,558.9 units/ml (&amp;lt;5 units/ml), C peptide was 1.9 ng/ml (0.5-2ng/ml), and Islet Antigen-2 (IA-2) autoantibody was &amp;lt;7.5 U/ml (0-7.49 U/ml). Despite positive antibodies, her C-peptide suggested enough beta-cell function, and she was switched from insulin to semaglutide. The patient was diagnosed with autoimmune diabetes, which may be from the COVID-19 infection, and was educated about regular follow-up and new medications like teplizumab that may help prevent the progression to needing insulin. Clinical Lesson: The exact mechanism of new-onset COVID-19-induced diabetes is still unknown. However, multiple risk factors are theorized to play a role in COVID-induced DM. These include defects in insulin production and glucose clearance, obesity, stress hyperglycemia, insulin resistance, and steroid therapy. Our patient had a history of obesity but no history of diabetes, steroid use, or any personal or family history of autoimmune processes. Compared to COVID-19 patients with normoglycemia or hyperglycemia, patients with preexisting diabetes and newly diagnosed diabetes experienced more severe complications, such as shock, ARDS, acute kidney injury, hypoalbuminemia, and severe COVID-19 complications. Additional research is required to investigate the various pathophysiologies and treatment options, including new medications that may prevent the disease's further progression. Diabetes caused by COVID-19 should be treated cautiously, and prompt diagnosis and care are essential to preventing further complications. Presentation: 6/3/2024

Endothelial cell senescence contributes to pathological retinal angiogenesis

AbstractBackgroundPathological retinal neovascularization is marked by microvascular lesions manifested initially as endothelial cell dysfunction and metabolic disturbances. However, the regulatory mechanism guiding retinal vascular endothelial cell function remian controversial.Main bodyPrevious studies have demonstarted that high glucose or oxidative stress can induce premature senescence in endothelial cells, triggering inflammatory responses within the vascular system and promoting the secretion of pro‐inflammatory factors, ultimately leading to pathological angiogenesis. Endothelial cell senescence has thus become a key target for anti‐angiogenic therapies.ConclusionThis review delves into current research on the mechanisms driving senescence‐induced retinal angiogenesis and highlights potential target protein pathways, aiming to provide insights for future investigations.

The Effects of Music Therapy on Self-Management, Depression, and Stress in Patients with Type 2 Diabetes Mellitus

Background: Among type 2 diabetes patients hospitalized for blood sugar control, stress and depression are high and have a negative effect on blood sugar control. Therefore, this study sought to determine whether listening to music helps reduce stress and depression and affects blood sugar control.Methods: This is a randomized, controlled, pre- and post-design study conducted from April 2017 to September 2019 in patients with type 2 diabetes hospitalized for blood glucose control at Kyung Hee University Hospital at Gangdong. After diabetes education was provided to both the control and experimental groups, the experimental group listened to music for 30 minutes a day with a tablet PC and the control group was prohibited from listening to music during the study period. Stress was evaluated using the PAID (Problem Areas in Diabetes) scores, depression using the CES-D (Center for Epidemiologic Studies Depression) scale, and self-management using the SDSCA (Summary of Diabetes Self-Care Activities) questionnaire.Results: A total of 59 patients (41.5 ± 12.6 years, 75.0% male) were enrolled and randomized into the control group (n = 28) and experimental group (n = 31). Music therapy had no statistically significant relationship with blood sugar (&lt;i&gt;P&lt;/i&gt; = 0.887), depression (&lt;i&gt;P&lt;/i&gt; = 0.248), stress (&lt;i&gt;P&lt;/i&gt; = 0.994), or self-management (&lt;i&gt;P&lt;/i&gt; = 0.959). However, in both groups, blood glucose control, stress, and self-management were all significantly improved at discharge compared to at the beginning of hospitalization (&lt;i&gt;P&lt;/i&gt; = 0.031).Conclusion: It was confirmed that intensive medical treatment and diabetes education for hospitalized patients with type 2 diabetes improved not only blood glucose control but also depression, stress, and self-management, regardless of listening to music.

Relationship of paraoxonase-1 and paraoxonase-3 with routine laboratory tests and oxidative stress in type 2 diabetes mellitus

Abstract Objectives We aimed to investigate the relationship between serum paraoxonase-1 (PON1) and paraoxonase-3 (PON3) levels and activities with hemoglobin A1c (HbA1c), serum fasting blood glucose, lipid profile, and oxidative stress in patients with type 2 diabetes mellitus (T2DM). Also, we aimed to examine PON1 and PON3 levels and activities in these patients according to the HbA1c goal in diabetes treatment and PON1192 phenotypes. Methods One hundred forty-one volunteers diagnosed with T2DM participated in this study. Serum PON1 and PON3 levels and activities, total oxidant status (TOS), and total antioxidant status (TAS) were measured. PON1192 phenotypes were determined by using PON1 activities. Also, HbA1c, serum fasting blood glucose, and lipid profile results, which were measured for routine examination on the same day as sample collection, were used for this study. Results There was a positive relationship between arylesterase and lactonase activities and high-density lipoprotein cholesterol (HDL-C), between lactonase activity and TAS, and a negative relationship between PON1 level and TAS in patients with T2DM. Our study also showed that PON3/HDL-C was higher in patients with HbA1c levels ≥7 %. Lactonase activities were higher in patients with PON1Q192Q and PON1Q192R phenotypes than in patients with PON1R192R phenotypes. Conclusions PON1 and PON3 levels and activities alone could not be associated with immediate or long-term blood glucose levels in patients with T2DM. Higher PON3/HDL-C in patients with HbA1c levels ≥7 % may show a protective role of PON3 in defense against higher glucose levels. Also, we found that the PON1192 phenotype can affect serum lactonase activity.

Therapeutic potential of aquatic Stevia extract in alleviating endoplasmic reticulum stress and liver damage in streptozotocin-induced diabetic rats.

Misfolded proteins accumulate in the liver due to endoplasmic reticulum stress (ERS) caused by high blood glucose levels in diabetes. This triggers the unfolded protein response (UPR), which if persistently activated, results in cellular dysfunction. Chronic ER stress increases inflammation, insulin resistance, and apoptosis. There is growing interest in using native plants and traditional medicine for diabetes treatment. The stevia plant has recently gained attention for its potential therapeutic effects. This study investigates the protective effects of aquatic stevia extract on liver damage, ER stress, and the UPR pathway in streptozotocin (STZ)-induced diabetic rats. Rats were randomly divided into four groups: a control group that received 1ml of water; a diabetic group induced by intraperitoneal injection of STZ (60mg/kg); a diabetic group treated with metformin (500mg/kg); and a diabetic group treated with aquatic extracts of stevia (400mg/kg). After 28 days, various parameters were assessed, including inflammatory markers, oxidative stress indices, antioxidant levels, gene expression, stereology, and liver tissue pathology. Compared to the diabetic control group, treatment with stevia significantly decreased serum glucose, liver enzymes, inflammatory markers, and oxidative stress while increasing body weight and antioxidant levels. Additionally, stevia extract manipulated UPR gene expression and reduced apoptosis pathway activation. Histological examination revealed improved liver tissue morphology in stevia-treated diabetic rats. These findings suggest that aquatic stevia extract mitigates ER stress in diabetic rats by modulating the IRE-1 arm of the UPR and apoptosis pathways, highlighting its potential therapeutic benefits for diabetes-related liver complications.

Genetic support of causal association between lipid and glucose metabolism and stress urinary incontinence in women: a bidirectional Mendelian randomization and multivariable-adjusted study.

Stress urinary incontinence (SUI) is a common condition characterized by urethral sphincter failure and urine leakage. Its prevalence in women is higher than in men, and estimates of crude prevalence rates vary widely due to factors such as research methodologies, study populations, and underreporting by patients. This variability hinders research and impacts patient diagnosis, treatment, and quality of life. The complex etiology of SUI is not fully understood, and previous studies have primarily focused on non-invasive indicators. While emerging observational research suggests a correlation between SUI in women and abnormalities in lipid and blood metabolism, the underlying biological mechanisms and causal relationships require further investigation. This study aims to explore the causalities between SUI in women and lipid and blood metabolism. Using bidirectional univariate Mendelian randomization (MR), we investigated the causal association between SUI liability in women (case/control = 5,924/399,509) from UK Biobank and lipid and glucose metabolism, indicated by total cholesterol (TC, N = 61,166), low-density lipoproteins (LDL, N = 58,381), high-density lipoproteins (HDL, N = 60,812), triglycerides (TG, N = 60,027), fasting glucose (FG, N = 19,745), and fasting insulin (FI, N = 38,238) from ENGAGE consortium. To account for potential confounding effects, multivariable MR (MVMR) analyses were performed, adjusting for body mass index (BMI) and separately among lipid and glucose metabolism. We found that increased genetically proxied TC, LDL, and HDL levels were associated with an elevated risk of SUI in women (OR: 1.090-1.117, all P < 0.05), These associations were further supported by MVMR analyses with adjustment for BMI (OR: 1.087-1.114, all P < 0.05). Conversely, increased FG and FI were associated with reduced SUI reliability in women (OR: 0.731-0.815, all P < 0.05). When adjusting among lipid and glucose metabolism, only HDL and FI demonstrated causal effects. Reverse MR analyses provided no genetic evidence supporting the causal effect of SUI in women on lipid and blood metabolism (all P > 0.05). Our results reported that increased TC, LDL, and HDL are linked to higher SUI susceptibility in women, while higher FG and FI levels have a protective effect. In overweight/obese women with metabolic abnormalities, the positive associations between TC, LDL, and HDL levels and SUI indicate a higher risk.

The effects of spirulina (Arthrospira platensis) supplementation on serum fasting blood glucose, lipid parameters, and oxidative stress markers in male rats with type 2 diabetes

Background. Some studies have shown that Spirulina has biological properties exerting beneficial effects on human health. This study aimed to evaluate the effects of Spirulina supplementation on serum glucose, lipid parameters, and oxidative stress markers in male rats with streptozotocin/nicotinamide–induced T2DM. Methods. In this experimental study, rats with diabetes were divided into six groups: healthy control, diabetic control, diabetic-metformin, diabetic-Spirulina 100 mg/dL, diabetic-Spirulina 200 mg/dL, and healthy control-Spirulina 200 mg/d. At the end of the study (28 days), the blood samples were collected, and the fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined. Results. Significant reductions (P&lt;0.001) were found in serum level of FBG in Metformin and Spirulina 100 mg/kg compared with diabetic control group. The groups were different regarding the serum levels of HDL-C post-intervention. ANOVA analysis also showed significant differences between the Spirulina 100 mg/kg or Metformin group and diabetic control group regarding the serum level of MDA (P&lt;0.05). Conclusion. Spirulina at a dose of 100 mg/kg may have contributed to controlling the fasting blood glucose and oxidative stress. Practical Implications. Our study results suggested that Spirulina, as a promising agent, at lower doses may have been considered as a functional food for the management of diabetes mellitus.

Hyperglycemic environments directly compromise intestinal epithelial barrier function in an organoid model and hyaluronan (∼35 kDa) protects via a layilin dependent mechanism

BackgroundMetabolic syndrome and diabetes in obese individuals are strong risk factors for development of inflammatory bowel disease (IBD) and colorectal cancer. The pathogenic mechanisms of low-grade metabolic inflammation, including chronic hyperglycemic stress, in disrupting gut homeostasis are poorly understood. In this study, we sought to understand the impact of a hyperglycemic environment on intestinal barrier integrity and the protective effects of small molecular weight (35 kDa) hyaluronan on epithelial barrier function. MethodsIntestinal organoids derived from mouse colon were grown in normal glucose media (5 mM) or high glucose media (25 mM) to study the impact of hyperglycemic stress on the intestinal barrier. Additionally, organoids were pretreated with 35 kDa hyaluronan (HA35) to investigate the effect of hyaluronan on epithelial barrier under high glucose stress. Immunoblotting as well as confocal imaging was used to understand changes in barrier proteins, quantitative as well as spatial distribution, respectively. Alterations in barrier function were measured using trans-epithelial electrical resistance and fluorescein isothiocyanate flux assays. Untargeted proteomics analysis was performed to elucidate mechanisms by which HA35 exerts a protective effect on the barrier. Intestinal organoids derived from receptor knockout mice specific to various HA receptors were utilized to understand the role of HA receptors in barrier protection under high glucose conditions. ResultsWe found that high glucose stress decreased the protein expression as well as spatial distribution of two key barrier proteins, zona occludens-1 (ZO-1) and occludin. HA35 prevented the degradation or loss of ZO-1 and maintained the spatial distribution of both ZO-1 and occludin under hyperglycemic stress. Functionally, we also observed a protective effect of HA35 on the epithelial barrier under high glucose conditions. We found that HA receptor, layilin, was involved in preventing barrier protein loss (ZO-1) as well as maintaining spatial distribution of ZO-1 and occludin. Additionally, proteomics analysis showed that cell death and survival was the primary pathway upregulated in organoids treated with HA35 under high glucose stress. We found that XIAP associated factor 1 (Xaf1) was modulated by HA35 thereby regulating apoptotic cell death in the intestinal organoid system. Finally, we observed that spatial organization of both focal adhesion kinase (FAK) as well as F-actin was mediated by HA35 via layilin. ConclusionOur results highlight the impact of hyperglycemic stress on the intestinal barrier function. This is of clinical relevance, as impaired barrier function has been observed in individuals with metabolic syndrome. Additionally, we demonstrate barrier protective effects of HA35 through its receptor layilin and modulation of cellular apoptosis under high glucose stress.

Research on the role of exosomes secreted by immortalized adipose-derived mesenchymal stem cells differentiated into pericytes in the repair of high glucose-induced retinal vascular endothelial cell damage

Diabetic retinopathy, a leading cause of vision impairment, is marked by microvascular complications in the retina, including pericyte loss, a key indicator of early-stage disease. This study explores the therapeutic potential of exosomes derived from immortalized adipose-mesenchymal stem cells differentiated into pericyte-like cells in restoring the function of mouse retinal microvascular endothelial cells damaged by high glucose conditions, thereby contributing to the understanding of early diabetic retinopathy intervention strategies. To induce immortalized adipose-mesenchymal stem cells differentiation into pericyte-like cells, the study employed pericyte growth supplement. And confirmed the success of cell differentiation through the detection of α-smooth muscle actin and neural/glial antigen 2 expression by Western blot and immunofluorescence. Exosomes were isolated from the culture supernatant of immortalized adipose-mesenchymal stem cells using ultracentrifugation and characterized through Western blot for exosomal markers (CD9, CD81, and TSG101), transmission electron microscopy, and nanoparticle tracking analysis. Their influence on mouse retinal microvascular endothelial cells under high glucose stress was assessed through various functional assays. Findings revealed that exosomes, especially those from pericyte-like immortalized adipose-mesenchymal stem cells, were efficiently internalized by retinal microvascular endothelial cells and effectively counteracted high glucose-induced apoptosis. These exosomes also mitigated the rise in reactive oxygen species levels and suppressed the migratory and angiogenic properties of retinal microvascular endothelial cells, as demonstrated by Transwell and tube formation assays, respectively. Furthermore, they preserved endothelial barrier function, reducing hyperglycemia-induced permeability. At the molecular level, qRT-PCR analysis showed that exosome treatment modulated the expression of critical genes involved in angiogenesis (VEGF-A, ANG2, MMP9), inflammation (IL-1β, TNF-α), gap junction communication (CX43), and cytoskeletal regulation (ROCK1), with the most prominent effects seen with exosomes from pericyte-like immortalized adipose-mesenchymal stem cells. High glucose increased the expression of pro-angiogenic and pro-inflammatory markers, which were effectively normalized post-exosome treatment. In conclusion, this research highlights the reparative capacity of exosomes secreted by pericyte-like differentiated immortalized adipose-mesenchymal stem cells in reversing the detrimental effects of high glucose on retinal microvascular endothelial cells. By reducing apoptosis, oxidative stress, inflammation, and abnormal angiogenic behavior, these exosomes present a promising avenue for therapeutic intervention in early diabetic retinopathy. Future studies can focus on elucidating the precise molecular mechanisms and exploring their translational potential in vivo.

The association between triglyceride -glucose index and stress urinary incontinence in adult American women: A population-based study.

This investigation seeks to determine the triglyceride glucose (TyG) index's link to stress urinary incontinence (SUI) in American females of adult age. The investigation relied on data acquired via the National Health and Nutrition Examination Survey (NHANES) conducted over the period from 2011 to 2018. The independent relationship between TyG index and SUI was tested using multivariate logistic regression analysis. We applied a smooth curve fitting approach to analyze the interrelation of them. In addition, subgroup analysis was conducted and interaction experiments were conducted. Among 4459 female participants aged 20 and above, TyG index and SUI demonstrated a favorable correlation. Model 3 indicated that with every single-unit rise in the TyG index, the incidence of SUI increases by 18% [1.18 (1.01, 1.38)]. In contrast to individuals in the lowest tertile, subjects within the highest tertile of the TyG index exhibited a 68% increase in SUI incidence [1.68 (95% CI: 1.26, 2.23), 0.0004]. By using smooth curve fitting, a nonlinear positive evidence of an interconnection of the TyG index to SUI was identified. Women exhibiting increased TyG index levels are at a heightened risk of SUI. TyG index displays a stronger correlation than that observed with BMI. According to our findings, the TyG index is viewed as a potential tool for identifying SUI in women, and monitoring the value of TyG index may be helpful for predicting the occurrence of SUI.

From waste to wonder: exploring the hypoglycemic and anti-oxidant properties of corn processing by-products.

Introduction: The industrial processing of corn (Zeamays L.) generates by-products such as corn silk, straw peels, and straw core, which contribute to adverse environmental impacts. Our study aimed to investigate sustainable approaches for mitigating these effects by evaluating the hypoglycemic potential and mechanisms of ethyl acetate fractions derived from these corn derivatives. Methods: We employed glucose consumption assays, high glucose stress tests, UPLC-QE-Orbitrap-MS analysis, molecular docking, and simulations to assess their components and efficacy. Antioxidant capacities were evaluated using DPPH, FRAP, ABTS, and •OH scavenging assays. Results: Notably, the ethyl acetate fraction extracted from straw peels (SPE) exhibited a high concentration of flavonoids and phenolic compounds along with pronounced hypoglycemic activity and antioxidant capacity. SPE significantly enhanced glucose consumption in insulin-resistant HepG2 cells while protecting HUVECs against damage caused by high glucose levels. Molecular docking analyses confirmed the interaction between active compounds and α-glucosidase as well as α-amylase, while molecular dynamic simulations indicated stability at their binding sites. Discussion: In conclusion, the hypoglycemic and antioxidative properties observed in corn by-products such as straw peels, corn silk, and straw core can be attributed to the inhibition of α-glucosidase and α-amylase activities, coupled with their rich phenolic and flavonoid content. These findings highlight the potential of these by-products for applications in healthcare management and their sustainable utilization, demonstrating significant value in the use of agricultural residues.