Disruption Of Glucose Metabolism Research Articles

Exposure to 6-PPD quinone disrupts glucose metabolism associated with lifespan reduction by affecting insulin and AMPK signals in Caenorhabditis elegans

Glucose metabolism plays an important role for formation of normal physiological state of organisms. However, association between altered glucose metabolism and toxicity of 6-PPD quinone (6-PPDQ) remains largely unknown. In 1–100 μg/L 6-PPDQ exposed Caenorhabditis elegans, we observed increased glucose content. After 6-PPDQ exposure (1–100 μg/L), expressions of F47B8.10 and fbp-1 governing gluconeogenesis were increased, and expressions of hxk-1, hxk-3, pfk-1.1, pyk-1, and pyk-2 governing glycolysis were decreased. Under 6-PPDQ exposure condition, glucose content could be changed by RNAi of F47B8.10, hxk-1, and hxk-3, key genes for gluconeogenesis and glycolysis. In 6-PPDQ exposed nematodes, RNAi of daf-16 and aak-2 elevated glucose content, increased expressions of F47B8.10 and/or fbp-1, and decreased expressions of hxk-1, hxk-3, and/or pfk-1.1. Additionally, lifespan and locomotion during aging were increased by RNAi of F47B8.10 and decreased by RNAi of hxk-1 and hxk-3 in 6-PPDQ exposed nematodes. Moreover, after 6-PPDQ exposure, RNAi of F47B8.10 decreased expressions of insulin peptide genes (ins-7 and daf-28) and insulin receptor gene daf-2 and increased expressions of daf-16 and aak-2. In 6-PPDQ exposed nematodes, RNAi of hxk-1 and hxk-3 further increased expressions of ins-7, daf-28, and daf-2 and decreased expressions of daf-16 and aak-2. Our results demonstrated important association between altered glucose metabolism and toxicity of 6-PPDQ in inducing lifespan reduction in organisms.

Obstructive sleep apnea: Overlooked comorbidity in patients with diabetes

In this review article, we explore the interplay between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM), highlighting a significant yet often overlooked comorbidity. We delve into the pathophysiological links between OSA and diabetes, specifically how OSA exacerbates insulin resistance and disrupts glucose metabolism. The research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related complications. Emphasizing the importance of comprehensive management, including weight control and positive airway pressure therapy, the study advocates integrated approaches to improve outcomes for patients with T2DM and OSA. This review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

Intergenerational Impact of Parental Zinc Deficiency on Metabolic and Redox Outcomes in Drosophila melanogaster.

Zinc deficiency is a common nutritional disorder with detrimental health consequences. Whether parental zinc deficiency induces intergenerational effects remains largely unknown. We investigated the effects of a combined maternal and paternal zinc deficiency on offspring's metabolic outcomes and gene expression changes in Drosophila melanogaster. The parent flies were raised on zinc-deficient diets throughout development, and their progeny were assessed. Offspring from zinc-deprived parents exhibited a significant (p < 0.05) increase in body weight and whole-body zinc levels. They also displayed disrupted glucose metabolism, altered lipid homeostasis, and diminished activity of antioxidant enzymes. Gene expression analysis revealed significant (p < 0.05) alterations in zinc transport genes, with increases in mRNA levels of dZIP1 and dZnT1 for female and male offspring, respectively. Both sexes exhibited reduced dZnT35C mRNA levels and significant (p < 0.05) increases in the mRNA levels of DILP2 and proinflammatory markers, Eiger and UPD2. Overall, female offspring showed higher sensitivity to parental zinc deficiency. Our findings underscore zinc's crucial role in maintaining health and the gender-specific responses to zinc deficiency. There is the need for further exploration of the underlying mechanisms behind these intergenerational effects.

Role of polymeric immunoglobulin receptor in glucose metabolism

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fundación La Caixa 2022 HR22-0253. Comunidad de Madrid P2022/BMD-7333 INMUNOVAR-CM Background Type 2 diabetes and obesity are leading causes of death and disability worldwide, being both risk factors for cardiovascular disease. Intestinal immune system is being shown to have a key role in insulin resistance (IR). Polymeric immunoglobulin receptor (PIGR) is a transmembrane protein which facilitates the transcytosis of the soluble polymeric isoforms of immunoglobulin A (IgA) and is widely expressed in mucosal epithelial cells. IgA levels are reduced in obesity and the loss of IgA in mice worsens insulin resistance and increases inflammation in adipose tissue. However, the specific role of PIGR in IR has not been fully elucidated. Aim To analyze the role of PIGR in systemic glucose metabolism. Methods To determine the impact of global silencing of Pigr on whole-body glucose metabolism, we metabolically characterized the Pigr-/- female mouse 60% fat diet (HFD). We performed glucose and insulin tolerance tests. In vivo and ex vivo adiposity was measured by dual x-ray absorptiometry (DXA) and adipose tissue depots weight, fasting glucose and insulin plasma levels were determined at endpoint. Circulating IgA levels were measured by ELISA and IgA deposition in liver and adipose tissue of control and Pigr-/- mice was determined by western blot and immunohistochemistry. Results As previously described, we show that IgA serum levels were highly increased in Pigr -/- mice. Besides, we demonstrate that IgA deposition in liver and adipose tissue was increased in these mice. We demonstrate that global deletion of Pigr results in whole-body glucose intolerance and IR mice fed HFD. Fasting glucose levels (169.24±24.49 mg/dl in Pigr -/- mice vs 142±27mg/dl in control mice) and fasting insulin levels (1.27±0.42 ng/ml in Pigr -/- mice vs 0.92±0.37 ng/ml in control mice) were significantly increased in Pigr -/- mice fed HFD for 17 weeks. No differences were found in lipid profile levels (triglycerides, HDL-c, VLDL+LDL-c and NEFA). Interestingly, Pigr-/- mice show significant increased adiposity (46±4.11 % adiposity vs 50.6±4.9 in control) measured by DXA, which results in a significant increase in body weight (BW), compared to control (BW gain over 20 weeks on HFD: 21.85± 3.06 gr in Pigr -/- mice vs 17.93±2.1 gr). mRNA expression of the β isoform of carbohydrate responsive-element binding protein (ChREBPβ) is significantly reduced (0.5 folds vs control group) in Pigr -/- adipose tissue, which might link the whole-body metabolic phenotype to ChREBP-dependent glucose sensing by adipose tissue. Conclusion Global Pigr deletion results in whole-body glucose intolerance and IR in female mice fed HFD. Our results suggest cell-intrinsic mechanisms of Pigr deletion as well as extracellular components (increased IgA serum levels and deposition in tissues) as potential triggers of systemic glucose metabolism disruption. Management of PIGR levels might be key for glucose-metabolism-related pathologies.

Hypoxia-induced TRPM7 promotes glycolytic metabolism and progression in hepatocellular carcinoma

BackgroundHypoxia disrupts glucose metabolism in hepatocellular carcinoma (HCC). Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) plays an ontogenetic role. Thus, we aimed to explore the regulation of TRPM7 by hypoxia-induced factor (HIF) and its underlying mechanisms in HCC. Methodshypoxia was induced in multiple HCC cells using 1% O2 or CoCl2 treatment, and subsequently blocked using siRNAs targeting HIF-1α or HIF-2α as well as a HIF-1α protein synthesis inhibitor. The levels of HIF-1α and TRPM7 were assessed using quantitative PCR (qPCR) and Western blot analysis. Chromatin immunoprecipitation (ChIP) and luciferase assays were performed to observe the regulation of TRPM7 promoter regions by HIF-1α. A PCR array was utilized to screen glucose metabolism-related enzymes in HEK293 cells overexpressing TRPM7 induced by tetracycline, and then verified in TRPM7-overexpressed huh7 cells. Finally, CCK-8, transwell, scratch and tumor formation experiments in nude mice were conducted to examine the effect of TRPM7 on proliferation and metastasis in HCC. ResultsExposure to hypoxia led to increase the levels of TRPM7 and HIF-1α in HCC cells, which were inhibited by HIF-1α siRNA or enhanced by HIF-1α overexpression. HIF-1α directly bound to two hypoxia response elements (HREs) in the TRPM7 promoter. Several glycolytic metabolism-related enzymes, were simultaneously upregulated in HEK293 and huh7 cells overexpressing TRPM7 during hypoxia. In vitro and in vivo experiments demonstrated that TRPM7 promoted the proliferation and metastasis of HCC cells. ConclusionsTRPM7 was directly transcriptionally regulated by HIF-1α, leading to glycolytic metabolic reprogramming and the promotion of HCC proliferation and metastasis in vitro and in vivo. Our findings suggest that TRPM7 might be a potential diagnostic indicator and therapeutic target for HCC.

Phenotypes of streptozotocin-induced gestational diabetes mellitus in mice.

Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors increase GDM risk, a lack of suitable models impedes a comprehensive understanding of its pathology. To address this, we administered streptozotocin (STZ, 75 mg/kg) to C57BL/6N mice for two days before pregnancy, establishing a convenient GDM model. Pregnant mice exposed to STZ (STZ-pregnant) were compared with STZ-injected virgin mice (STZ-virgin), citrate buffer-injected virgin mice (CB-virgin), and pregnant mice injected with citrate buffer (CB-pregnant). STZ-pregnant non-obese mice exhibited elevated blood glucose levels on gestational day 15.5 and impaired glucose tolerance. They also showed fewer normal fetuses compared to CB-pregnant mice. Additionally, STZ-pregnant mice had the highest plasma C-peptide levels, with decreased pancreatic islets or increased alpha cells compared to CB-pregnant mice. Kidneys isolated from STZ-pregnant mice did not display histological alterations or changes in gene expression for the principal glucose transporters (GLUT2 and SGLT2) and renal injury-associated markers. Notably, STZ-pregnant mice displayed decreased gene expression of insulin-receiving molecules (ISNR and IGFR1), indicating heightened insulin resistance. Liver histology in STZ-pregnant mice remained unchanged except for a pregnancy-related increase in lipid droplets within hepatocytes. Furthermore, the duodenum of STZ-pregnant mice exhibited increased gene expression of ligand-degradable IGFR2 and decreased expression of GLUT5 and GLUT12 (fructose and glucose transporters, respectively) compared to STZ-virgin mice. Thus, STZ-pregnant mice displayed GDM-like symptoms, including fetal abnormalities, while organs adapted to impaired glucose metabolism by altering glucose transport and insulin reception without histopathological changes. STZ-pregnant mice offer a novel model for studying mild onset non-obese GDM and species-specific differences in GDM features between humans and animals.

Automated Multi-Injection Gas Chromatography-Photoionization Detection (AMI-GC-PID) for Qualitative and Quantitative Determination of Urinary Acetone

Acetone is produced from fat metabolism which is increased in diabetic patients due to the disruption of glucose metabolism. Therefore, urinary acetone is expected to be a biomarker for noninvasive diagnosis of diabetes. Although several techniques have been developed for urinary acetone, none meet the clinical needs of automated multi-injection for numerous samples. In this study, we developed automated multi-injection gas chromatography-photoionization detection (AMI-GC-PID) to determine urinary acetone. First, we optimized the sample preprocessing during urine collection and storage before detection and established a standard protocol. The urine was immediately sealed in headspace bottles, stored at 20 °C for 1 h, and equilibrated for 20 min at 80 °C before analysis. Next we evaluated the repeatability of the method and the influence of the urine matrix. The relative standard deviations (RSDs) of the intra-day (nine measurements) and inter-day (three days) measurements were less than 5%. The recovery rate was 97.4% ± 4.6%. AMI-GC-PID was applied to determine urinary acetone in 44 diabetic patients and 29 healthy subjects. The median concentration of urinary acetone was much higher in diabetic patients than in healthy controls (2019 μg/L compared 699 μg/L). The results show that AMI-GC-PID possesses suitable analytical figures of merit for urinary acetone with broad applications in the noninvasive diagnosis of diabetes.

Short Sleep Duration Disrupts Glucose Metabolism: Can Exercise Turn Back the Clock?

Short sleep duration is prevalent in modern society and may be contributing to type 2 diabetes prevalence. This review will explore the effects of sleep restriction on glycemic control, the mechanisms causing insulin resistance, and whether exercise can offset changes in glycemic control. Chronic sleep restriction may also contribute to a decrease in physical activity leading to further health complications.

Promising Phytoconstituents in Diabetes-related Wounds: Mechanistic Insights and Implications.

The onset of diabetes mellitus (DM), a metabolic disorder characterized by high blood glucose levels and disrupted glucose metabolism, results in 20% of people with diabetes suffering from diabetes-related wounds worldwide. A minor wound, such as a cut or abrasion, can lead to infections and complications in diabetic patients. We must understand the mechanism/s contributing to this delayed wound healing to develop effective prevention strategies. The potential benefits of bioactive phytochemicals for diabetic wound healing have been reported in numerous studies. A bioactive compound may have multiple actions, including antioxidants, antiinflammatory, antimicrobial, and angiogenesis. Compounds derived from these plants have shown promising results in wound healing, inflammation reduction, collagen synthesis, and neovascularization improvement. Consequently, this review provides an update to our understanding of how phytoconstituents promote wound healing in diabetics. A thorough literature review was conducted on diabetes, wound healing, and phytoconstituents for this study. Only English publications until June 2023 were included in the search, which used multiple search engines and the main keywords. Summing up, phytochemical-based interventions might improve the quality of life for diabetics by improving wound healing. However, to fully understand the efficacy and safety of these phytochemicals in managing diabetic wounds, more research and clinical trials are needed.

Cerebral Glucose Metabolism following TBI: Changes in Plasma Glucose, Glucose Transport and Alternative Pathways of Glycolysis-A Translational Narrative Review.

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism. After TBI, the brain undergoes dynamic changes in brain glucose transport, including alterations in glucose transporters and kinetics, and disruptions in the blood-brain barrier (BBB). In addition, cerebral glucose metabolism transitions from a phase of hyperglycolysis to hypometabolism, with upregulation of alternative pathways of glycolysis. Future research should further explore optimal, and possibly personalised, glycaemic control targets in TBI patients, with GLP-1 analogues as promising therapeutic candidates. Furthermore, a more fundamental understanding of alterations in the activation of various pathways, such as the polyol and lactate pathway, could hold the key to improving outcomes following TBI.

Prenylated flavonoid fractions from Glycyrrhiza glabra alleviate insulin resistance in HepG2 cells by regulating the ERK/IRS-1 and PI3K/Akt signaling pathways.

Insulin resistance (IR) is a key factor in the pathogenesis of disrupted glucose metabolism. Although the extract of Glycyrrhiza glabra has shown significant hypoglycemic activity, its bioactive components remain to be identified, and their mechanisms of action, especially on hepatocyte glucose metabolism, are yet to be explored. In the present study, the primary compounds from Glycyrrhiza glabra [named prenylated flavonoid fractions (PFFs)] have been identified and their chemical structures have been elucidated. The therapeutic effects of PFFs extracted from G. glabra on glucose metabolism disorders and IR in high insulin-induced insulin-resistant HepG2 (IR-HepG2) cells have been determined. Glabridin (GLD) was used as a control. The results indicated that, similar to GLD, PFFs increased glucose consumption, glucose uptake, and translocation of glucose transporter 4 to the plasma membrane in IR-HepG2 cells. In addition, they enhanced the activities of glycogen synthase, glucokinase, and pyruvate kinase, while reducing the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Furthermore, they activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and suppressed the extracellular signal-regulated kinase/insulin receptor substrate-1 (ERK/IRS-1) pathway. These findings suggest that, similar to GLD, PFFs can alleviate impaired glucose metabolism and alleviate IR in IR-HepG2 cells.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.The authors and their affiliations have been confirmed as correct.

The relation of C-reactive protein and impaired fasting glucose: Could it be a predictor for prediabetic state?

The rate of cardiovascular disease is increasing in developed countries progressively with estimates predicting 22 million by 2030. Based on these cardiovascular events lies atherosclerosis, a condition intricately linked to chronic inflammatory processes. Among fundamental clinical biomarkers, C-reactive protein (CRP) stands out as a backbone of inflammatory activity. Notably, the excessive production of CRP, often linked with obesity, plays a pivotal role in the dysregulation of triglyceride apo B-100 fractional catabolism, thus emerging as a significant cardiovascular risk factor. Apart from atherosclerotic processes, the interplay between high CRP levels and impaired fasting glucose (IFG) is also gaining recognition as a messenger of disrupted glucose metabolism, potentially ushering in the onset of a prediabetic state. Our retrospective analysis scrutinized the biochemical data - namely low-density lipoprotein cholesterol (LDL-C), triglycerides, fasting blood sugar, and CRP levels-of 3500 patients from an internal medicine outpatient clinic seen from August 2006 to May 2007. Our objective was to dissect the correlations among these parameters. Exclusion criteria were omitting individuals with acute or chronic inflammation, known inflammatory diseases, diagnosed diabetes, coronary artery disease, lipid metabolism disorders, those on lipid-lowering agents, and anyone outside the age bracket of 18-65 years. This study was conducted in strict adherence to the ethical principles outlined in the Declaration of Helsinki. As a result of our study, the ratio of CRP levels above 0.8 was significantly higher in patients with IFG according to the World Health Organization criteria (6.1-6.9 mmol/L or 109-124 mg/dL) than in individuals with normal fasting glucose (70-108 mg/dL). (19.7%, 17.2%, respectively) (p<0.001). In addition, the ratio of CRP levels above 0.8 was also higher in patients with triglyceride levels between 151 and 199 mg/dL) and over 500 mg/dL. (23.2%, 24.1%, respectively) (p<0.012). However, the relationship between CRP levels and LDL-C total cholesterol was not statistically significant (p>0.05). This retrospective study suggests the imperative for a proactive approach in the clinical evaluation of patients exhibiting elevated CRP, especially in the context of preemptive management of prediabetes. In light of these findings, we think that elevated CRP may be a warning sign for prediabetic status and may be useful in early diagnosis.

Pulmonary tuberculosis and diabetes mellitus: Epidemiology, pathogenesis and therapeutic management (Review).

The dual burden of pulmonary tuberculosis (PTB) and diabetes mellitus (DM) is a major global public health concern. There is increasing evidence to indicate an association between PTB and DM. DM is associated with immune dysfunction and altered immune components. Hyperglycemia weakens the innate immune response by affecting the function of macrophages, dendritic cells, neutrophils, and natural killer cells, and also disrupts the adaptive immune response, thus promoting the susceptibility of PTB in patients with DM. Antituberculosis drugs often cause the impairment of liver and kidney function in patients with PTB, and the infection with Mycobacterium tuberculosis weaken pancreatic endocrine function by causing islet cell amyloidosis, which disrupts glucose metabolism and thus increases the risk of developing DM in patients with PTB. The present review discusses the association between PTB and DM from the perspective of epidemiology, pathogenesis, and treatment management. The present review aims to provide information for the rational formulation of treatment strategies for patients with PTB-DM.

A Comprehensive Review of the Effects of Glycemic Carbohydrates on the Neurocognitive Functions Based on Gut Microenvironment Regulation and Glycemic Fluctuation Control.

Improper glycemic carbohydrates (GCs) consumption can be a potential risk factor for metabolic diseases such as obesity and diabetes, which may lead to cognitive impairment. Although several potential mechanisms have been studied, the biological relationship between carbohydrate consumption and neurocognitive impairment is still uncertain. In this review, the main effects and mechanisms of GCs' digestive characteristics on cognitive functions are comprehensively elucidated. Additionally, healthier carbohydrate selection, a reliable research model, and future directions are discussed. Individuals in their early and late lives and patients with metabolic diseases are highly susceptible to dietary-induced cognitive impairment. It is well known that gut function is closely related to dietary patterns. Unhealthy carbohydrate diet-induced gut microenvironment disorders negatively impact cognitive functions through the gut-brain axis. Moreover, severe glycemic fluctuations, due to rapidly digestible carbohydrate consumption or metabolic diseases, can impair neurocognitive functions by disrupting glucose metabolism, dysregulating calcium homeostasis, oxidative stress, inflammatory responses, and accumulating advanced glycation end products. Unstable glycemic status can lead to more severe neurological impairment than persistent hyperglycemia. Slow-digested or resistant carbohydrates might contribute to better neurocognitive functions due to stable glycemic response and healthier gut functions than fully gelatinized starch and nutritive sugars.

Associations of Glucometabolic Indices with Aortic Stiffness in Patients Undergoing Peritoneal Dialysis with and without Diabetes Mellitus

Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (β = 0.52, 95% confidence interval [CI] = 0.01–1.03, p = 0.046), high HOMA-IR (β = 0.60, 95% CI = 0.12–1.08, p = 0.015), and a high PD glucose load (β = 0.58, 95% CI = 0.08–1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness.

Tetraarsenic tetrasulfide triggers ROS-induced apoptosis and ferroptosis in B-cell acute lymphoblastic leukaemia by targeting HK2

PurposeAcute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children. Despite cure rates of higher than 85 %, refractory or relapsed ALL still exhibits a bleak prognosis indicative of the dearth of treatment modalities specific for relapsed or refractory ALL. Prior research has implicated metabolic alterations in leukemia pathogenesis, and literature on the therapeutic efficacy of arsenic compounds targeting metabolic pathways in B-cell acute lymphoblastic leukemia (B-ALL) cells is scarce. MethodsA compound extracted from realgar, tetraarsenic tetrasulfide (As4S4), and its antitumor effects on B-ALL were experimentally examined in vitro and in vivo. ResultsAs4S4 apparently targets B-ALL cells by inducing specific cellular responses, including apoptosis, G2/M arrest, and ferroptosis. Interestingly, these effects are attributed to reactive oxygen species (ROS) accumulation, and increased ROS levels have been linked to both the mitochondria-dependent caspase cascade and the activation of p53 signaling. The ROS scavenger N-acetylcysteine (NAC) can counteract the effects of As4S4 treatment on Nalm-6 and RS4;11 cells. Specifically, by targeting Hexokinase-2 (HK2), As4S4 induces alterations in mitochondrial membrane potential and disrupts glucose metabolism, leading to ROS accumulation, and was shown to inhibit B-ALL cell proliferation in vitro and in vivo. Intriguingly, overexpression of HK2 can partially desensitize B-ALL cells to As4S4 treatment. ConclusionTetraarsenic tetrasulfide can regulate the Warburg effect by controlling HK2 expression, a finding that provides both new mechanistic insight into metabolic alterations and pharmacological evidence for the clinical treatment of B-ALL.

DEHP and DBP, common phthalates, induce glucose metabolism disorders in rats via oxidative damage of PI3K/Akt/GLUT4 signaling

Phthalic acid esters (PAEs) are environmental endocrine disruptors thought to interfere with glucose metabolism in humans. Most of the related research has focused on population epidemiological studies, with the underlying mechanisms remaining unresolved. Using an in vivo animal model, we examined the effects of oral administration of two commonly used PAEs [di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP)] on glucose homeostasis and insulin secretion. DEHP (750 mg/kg, 1/40 LD50), DBP (500 mg/kg, 1/40 LD50), and DEHP (750 mg/kg) + DBP (500 mg/kg) exert an influence on glucose metabolism and elicit a reduction in insulin sensitivity in rats. Furthermore, these substances induce detrimental effects on the structure and functionality of pancreatic β-cells. DEHP and/or DBP triggered an increase in plasma malondialdehyde (MDA) and reduction in superoxide dismutase (SOD) activity; a reduction in the phosphorylation of phosphatidyl inositol 3 kinase (PI3K) and phospho-protein kinase B (p-Akt473) proteins; an increase in the relative expression of Bax, Caspase-8, cleaved-Caspase-9, and cleaved-Caspase-3; and a reduction in the relative expression of Bcl-2-related Bax in pancreatic tissue and of gastrocnemius glucose transporter 4 (GLUT4) in the gastrocnemius muscle. Based on these findings, these PAEs can disrupt glucose metabolism, possibly via oxidative damage of the PI3K/Akt/GLUT4 pathway; this damage induces pancreatic β-cell apoptosis, affects pancreatic β-cell function, and affects glucose metabolism and insulin resistance in rats. To the best of our knowledge, this study was the first to show that the combined effect of the two PAEs affects glucose metabolism and insulin resistance in rats that is significantly higher than the effects of each PAE. Thus, safety standards and studies do not consider this effect as a significant oversight when blending PAEs. We assert that this must be addressed and corrected for establishing more impactful and safer standards.

P-coumaric acid ameliorates Aβ25–35-induced brain damage in mice by modulating gut microbiota and serum metabolites

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aβ25–35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aβ25–35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aβ25–35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aβ25–35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aβ25–35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.

Promoting Diabetes Self-Management in a Psychiatric Hospital.

Type 2 diabetes and psychiatric illnesses have a bidirectional association, influencing each other in direct but independent ways. People with psychiatric illnesses are more likely than the general population to develop type 2 diabetes, in part because antipsychotic medications affect the metabolic system, disrupting glucose metabolism, and also because they lack diabetes self-management education and self-care skills. This study assessed the effectiveness of diabetes self-management education and support (DSMES) in patients with mental illness and diabetes using the Diabetes Self-Management Questionnaire. Analysis of paired responses to the pre- and post-DSMES survey questions showed a statistically significant increase in diabetes self-management knowledge after participation in the education sessions. These results emphasized the importance of DSMES in strengthening patients' knowledge and skills, with additional support from their psychiatrist and medical team.

Effects of High Dietary Carbohydrate Levels on Growth Performance, Enzyme Activities, Expression of Genes Related to Liver Glucose Metabolism, and the Intestinal Microbiota of Lateolabrax maculatus Juveniles

The present study was conducted to investigate the effects of high dietary carbohydrate levels on growth performance, enzyme activities, and gene expressions related to liver glucose metabolism and the intestinal microbiota of Lateolabrax maculatus juveniles. Two experimental diets with levels of carbohydrates (20% and 30%, named the NCD group and the HCD group, respectively) were designed to feed L. maculatus (initial weight 9.45 ± 0.03 g) for 56 days. The results showed that, compared with the NCD group, the condition factor (CF) was significantly elevated in the HCD group (p &lt; 0.05). The plasma advanced glycosylation end products (AGEs), glycated serum protein (GSP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glutamate aminotransferase (AST) were significantly higher in the HCD group than those in the NCD group (p &lt; 0.05). The intestinal lipase, chymotrypsin, and α-amylase in the HCD group were significantly higher than those in the NCD group (p &lt; 0.05). The liver superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and catalase (CAT) were significantly lower in the HCD group than in the NCD group (p &lt; 0.05). The liver malondialdehyde (MDA) and hexokinase (HK) levels were significantly higher than those in the NCD group (p &lt; 0.05). In the histopathological findings, liver cells in the HCD group appeared to have many vacuoles, and the number of lipid droplets increased. Compared with the NCD group, the relative expression of liver glucokinase (GK) and glycogen synthetase kinase-3 (GSK3β) genes in the HCD group was significantly increased (p &lt; 0.05), while the relative expression of phosphoenolpyruvate carboxykinase (PEPCK) and glycogen phosphorylase (GP) genes in the HCD group was significantly reduced (p &lt; 0.05). High-throughput 16S rRNA gene sequencing showed that high dietary carbohydrate intake changed the composition and structure of the intestinal microbiota. At the phylum level of the intestinal microbiota, high dietary carbohydrates decreased the relative abundance of Firmicutes and increased the relative abundance of Proteobacteria and Bacteroidetes. At the genus level of the intestinal microbiota, high carbohydrates decreased the relative abundance of Bacillus and increased the relative abundance of Photobacterium and Paraclostridium. From the results of this experiment on L. maculatus, high carbohydrates led to increased condition factor and liver glycogen, lipid deposition, decreased antioxidant capacity of the liver, increased relative abundance of harmful intestinal microorganisms, and disrupted glucose metabolism.