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Background: Recent studies indicated that bioactive lipids of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) predict unhealthy metabolic phenotypes, but results remain inconsistent. To fill this knowledge gap, we investigated whether essential trace elements affect PC-Lyso PC remodeling pathways and the risk of insulin resistance (IR)., Methods: Anthropometric and blood biochemical data (glucose, insulin, and lipoprotein-associated phospholipase A2 (Lp-PLA2)) were obtained from 99 adults. Blood essential/probably essential trace elements and lipid metabolites were respectively measured by inductively coupled plasma mass spectrometry (ICP-MS), and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)., Result and Conclusion: Except for LysoPC (O-18:0/0:0), an inverse V shape was observed between body weight and PC and LysoPC species. A Pearson correlation analysis showed that essential/probably-essential metals (Se, Cu, and Ni: r=-0.4∼-0.7) were negatively correlated with PC metabolites but positively correlated with LysoPC (O-18:0/0:0) (Se, Cu, and Ni: r=0.85-0.64). Quantile-g computation showed that one quantile increase in essential metals was associated with a 2.16-fold increase in serum Lp-PLA2 (β=2.16 (95 % confidence interval (CI): 0.34, 3.98), p=0.023), which are key enzymes involved in PC/Lyso PC metabolism. An interactive analysis showed that compared to those with the lowest levels (reference), individuals with the highest levels of serum PCs (pooled, M2) and the lowest essential/probably essential metals (M1) were associated with a healthier body composition and had a 76 % decreased risk of IR (odds ratio (OR)=0.24 (95 % CI: 0.06, 0.90), p<0.05). In contrast, increased exposure to LysoPC(O-18:0/0:0) (M2) and essential metals (M2) exhibited an 8.22-times highest risk of IR (OR= 8.22 (2.07, 32.57), p<0.05) as well as an altered body composition. In conclusion, overexposure to essential/probably essential trace elements may promote an unhealthy body weight and IR through modulating PC/LysoPC remodeling pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50-70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a blue-green alga that may increase insulin sensitivity. Therefore, our study aims to evaluate SP as an alternative treatment to Met for improving glucose homeostasis by assessing the expression of 11 crucial genes involved in the insulin signaling pathway. After induction of the PCOS model using dehydroepiandrosterone (DHEA) (60 mg/kg bwt) for 30 consecutive days, rats were allocated into six groups. Relative liver weight, glutamic pyruvic transaminase (GPT) serum levels, glutamic-oxaloacetic transaminase (GOT), and insulin were determined. Furthermore, the gene expression of Ins1, Irs1, Pik3ca, Prkcz, Foxo1, Srebf1, Ppargc1a, Pklr, Gk, G6pc, and Pepck in the rat's liver tissue was determined using qRT-PCR. Treatment of the PCOS control group with Met or SP revealed a decrease in all these parameters compared with the PCOS model. Additionally, we found a statistically significant difference in the expression of both the Gk and Prkcz genes. To summarize our study results, SP or Met supplementation to PCOS rats had almost the same effect on assessed relative liver weight, GOT, GPT, and insulin levels compared with PCOS control rats. If further studies confirm and detect more impact of SP on IR in PCOS, SP could be used instead of Met since the latter causes many side effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The cytokine interleukin-38 (IL-38), a recently discovered member of the IL-1 family, has been shown to regulate inflammation and improve hepatic endoplasmic reticulum stress and lipid metabolism in individuals with obesity. However, its impact on insulin signaling in skeletal muscle cells and the underlying mechanisms remain unclear. In vitro obesity models were established using palmitate treatment, and Western blot analysis was performed to assess target proteins. Commercial kits were used to measure glucose uptake in cultured myocytes. Our study showed that IL-38 treatment alleviated the impairment of insulin signaling, including IRS-1 and Akt phosphorylation, and increased glucose uptake in palmitate-treated C2C12 myocytes. Increased levels of STAT3-mediated signaling and oxidative stress were observed in these cells following palmitate treatment, and these effects were reversed by IL-38 treatment. In addition, IL-38 treatment upregulated the expression of PPARδ, SIRT1 and antioxidants. Knockdown of PPARδ or SIRT1 using appropriate siRNAs abrogated the effects of IL-38 on insulin signaling, oxidative stress, and the STAT3-dependent pathway. These results suggest that IL-38 alleviates insulin resistance by inhibiting STAT3-mediated signaling and oxidative stress in skeletal muscle cells through PPARδ/SIRT1. This study provides fundamental evidence to support the potential use of IL-38 as a safe therapeutic agent for the treatment of insulin resistance and type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In type 2 diabetes mellitus, hepatic insulin resistance is intricately associated with oxidative stress and inflammation. Nonetheless, the lack of therapeutic interventions directly targeting hepatic dysfunction represents a notable gap in current treatment options. Flavonoids have been explored due to their potential antidiabetic effects. However, these compounds are associated with low bioavailability and high metabolization. In the present study, four flavonoids, kaempferol, quercetin, kaempferol-7-O-glucoside and quercetin-7-O-glucoside, were studied in a cellular model of hepatic insulin resistance using HepG2 cells. Quercetin was selected as the most promising flavonoid and incorporated into liposomes to enhance its therapeutic effect. Quercetin liposomes had a mean size of 0.12 µm, with an incorporation efficiency of 93 %. Quercetin liposomes exhibited increased efficacy in modulating insulin resistance. This was achieved through the modulation of Akt expression and the attenuation of inflammation, particularly via the NF-κB pathway, as well as the regulation of PGE 2 and COX-2 expression. Furthermore, quercetin liposomes displayed a significant advantage over free quercetin in attenuating the production of reactive pro-oxidant species. These findings open new avenues for developing innovative therapeutic strategies to manage diabetes, emphasizing the potential of quercetin liposomes as a promising approach for targeting both hepatic insulin resistance and associated inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Insulin resistance is the primary contributor to the disruption in glucose homeostasis in the body, playing a significant causative role in many metabolic diseases. Insulin resistance is characterized by compensatory insulin secretion and reduced insulin responsiveness in target organs. Dysregulation of the interaction between insulin-secreting cells and insulin-responsive target organs is an important factor driving the progression of insulin resistance. Circulating endocrine hormones are important mediators mediating the interaction between insulin-secreting cells and insulin-responsive target organs. In addition to the classical hormones secreted by endocrine glands and organ-specific hormones secreted by metabolism-related organs (adipose tissue, muscle, liver, etc.), extracellular vesicles have been recognized as a novel class of endocrine hormones with a complex composition. Extracellular vesicles can transport signaling molecules, such as miRNAs and LncRNAs, to vital organs related to insulin resistance, in a manner akin to conventional hormones. The significant role in regulating the development of insulin resistance underscores the increasing interest in extracellular vesicles as essential contributors to this process. In this review, we summarize the three types of hormones (classical hormones, organokines and extracellular vesicles) that play a regulatory role in insulin resistance, and focus on the novel endocrine hormones, extracellular vesicles, to elaborate the mechanism of extracellular vesicles' regulation of insulin resistance progress from two aspects: the impact on insulin-secreting cells and the influence on insulin-responsive target organs. In addition, this paper outlines the clinical applications of extracellular vesicles in insulin resistance. A comprehensive understanding of the regulatory mechanisms and diagnostic status of the inter-organ network in insulin resistance has great potential to advance targeted therapeutic interventions and diagnostic markers, thereby benefiting both the prevention and treatment of insulin resistance., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The global prevalence of Metabolic Syndrome (MetS) is continuously rising and exposure to environmental toxicants such as arsenic could be contributing to this rapid surge. In this study, we have assessed the effects of prenatal arsenic exposure on insulin resistance and MetS parameters in a mouse model, and an underlying mechanism was identified. We found that prenatal arsenic exposure promotes insulin resistance and adipocyte dysfunction which leads to the early onset of MetS in male offspring. Primary adipocytes isolated from 20-week-old arsenic-exposed offspring showed hypertrophy, elevated basal lipolysis, and impaired insulin response along with enhanced expression of Tumor necrosis factor-alpha (TNF-α). TNF-α levels were consistently high at gestational day 15.5 (GD15.5) as well as primary adipocytes of 6-week-old arsenic-exposed male offspring. Along with TNF-α, downstream p-JNK1/2 levels were also increased, which led to inhibitory phosphorylation of IRS1and reduced GLUT4 translocation upon insulin stimulation in adipocytes. Insulin response and downstream signaling were restored upon TNF-α inhibition, confirming its central role. The persistent overexpression of TNF-α in adipocytes of arsenic-exposed mice resulted from diminished EZH2 occupancy and reduced H3K27me3 (gene silencing histone marks) at the TNF-α promoter. This further led to chromatin relaxation, recruitment of c-Jun and CBP/p300, formation of an enhanceosome complex, and TNF-α expression. Our findings show how prenatal arsenic exposure can epigenetically modulate TNF-α expression to promote adipocyte dysfunction and insulin resistance which contributes to the early onset of MetS in offspring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the effect of insulin resistance (IR) on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in patients with polycystic ovary syndrome (PCOS)., Study Design: PubMed, Google Scholar,Web of Science, Embase, Scopus and the Cochrane Library were searched to identify relevant studies. A total of 6,137 PCOS women undergoing IVF/ICSI with or without IR were included in the systematic review and meta-analysis., Results: The systematic review and meta-analysis included twelve observational studies that were free from inherent bias. When comparing PCOS women undergoing IVF/ICSI, the IR and non-IR groups did not show significant differences in oocytes retrieved (WMD = -0.63, 95 % CI: -2.37 to 1.12, P = 0. 483), fertilization rate (WMD = 1.01, 95 % CI: -0.66 to 2.67, P = 0.236; OR = 0.97, 95 % CI: 0.79 to 1.19, P = 0.783), and live birth rate (OR = 1.02, 95 % CI: 0.78 to 1.33, P = 0.892). However, the group with IR had a lower number of MII oocytes (WMD = -1.07, 95 % CI: -1.54 to -0.59, P < 0.001), total embryos (WMD = -1.37, 95 % CI: -1. 78 to -0.95, P < 0.001), and clinical pregnancy rate (OR = 0.77, 95 % CI: 0.59 to 0.99, P = 0.042), as well as a higher miscarriage rate (OR = 1.11, 95 % CI: 1.02 to 1.22, P = 0.017) compared to the non-IR group., Conclusion: In women with PCOS, IR had a negative impact on IVF/ICSI outcomes. To obtain more favourable empirical support, larger studies are necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To our knowledge, no evidence exists to link dietary inflammatory potential to cardiovascular disease (CVD) in China. Furthermore, the precise mechanisms underlying the link between a pro-inflammatory diet and CVD remain incompletely understood., Objective: We aimed to investigate the relationship between dietary inflammatory potential and nonfatal CVD in the Chinese population and to explore the mediating role of insulin resistance., Methods: A total of 4822 adults who participated in the China Health and Nutrition Survey (CHNS) were included in this analysis. The dietary inflammatory index (DII) was used to assess dietary inflammatory potential. Cox proportional hazards models and restricted cubic spline were applied to assess the longitudinal associations. The triglyceride-glucose (TyG) index was calculated to measure insulin resistance. Mediation analysis using a two-stage regression method for survival data was employed to explore the mediating effects of the TyG index on the association between DII score and nonfatal CVD., Results: During a median follow-up of 18 y, 234 incident cases of nonfatal CVD, including 136 strokes and 114 myocardial infarctions (MIs), were observed. For each standard deviation of the DII score, nonfatal CVD incidence increased by 15% (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.31), and stroke incidence increased by 22% (HR = 1.22, 95% CI: 1.03-1.45). DII score displayed a linear association with nonfatal CVD and stroke (P for nonlinearity = 0.250 and 0.238, respectively). No significant association was found between the DII score and MI. Mediation analyses showed that the TyG index mediated 5.90% and 9.35% of the total association between DII score and nonfatal CVD and stroke, respectively., Conclusions: This study provides evidence that dietary inflammatory potential is positively associated with nonfatal CVD and stroke in Chinese adults, and the association was partly mediated by insulin resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aims: Remnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality., Methods: We conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality., Results: We identified an association between higher HOMA2-IR and higher RC levels. The effect of IR on CVD mortality was predominant (HR 1.32, 95%CI 1.18-1.48) and decreased at older ages (HR 0.934, 95%CI 0.918-0.959) compared to RC (HR 0.983, 95%CI 0.952-1.014). Higher risk of CVD mortality was observed in individuals with IR but normal RC (HR 1.37, 95%CI 1.25-1.50) and subjects with IR and high RC (HR 1.24, 95%CI 1.13-1.37), but not in subjects without IR but high RC. In mediation models, HOMA2-IR accounted for 78.2% (95%CI 28.11-98.89) of the effect of RC levels on CVD mortality., Conclusions: Our findings suggest that RC potentiates the risk of CVD mortality through its effect on whole-body insulin sensitivity, particularly among younger individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cyclocarya paliurus (Batal.) leaves, which contain a range of bioactive compounds, have been used as a traditional Chinese medicine homologous food since ancient times. However, there is a paucity of literature on comprehensive studies of alkaloids in the leaves of Cyclocarya paliurus (Batal.). For the first time, this study aimed to discover and identify alkaloids extracted from Cyclocarya paliurus (Batal.) leaves by ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-QTOF-MS). A total of ten alkaloids have been identified from Cyclocarya paliurus (Batal.) leaves based on accurate mass spectra (mass accuracy, isotopic spacing and distribution) and comparison to fragmentation spectra reported in the literature. In vitro, alkaloids alleviated insulin resistance by increasing glucose consumption and glycogen content in insulin resistance HepG2 cells. The RNA-seq and western blotting results showed that alkaloids could upregulate the expression of phosphatidylinositol 3-kinase (PI3K), and increase the phosphorylation of insulin receptor protein kinase B (AKT). This study not only clarified the chemical constituents and revealed that diverse alkaloids also presented from Cyclocarya paliurus (Batal.) leaves, also, it will provide chemical information on potential compounds for developing new drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: Our study aimed to analyze how hepatic insulin resistance (IR) influences the efficacy of 48 weeks of metformin treatment in newly diagnosed type 2 diabetes patients., Methods: We chose 291 participants who were allocated to a 48-week metformin treatment in the "Metformin and Acarbose in Chinese as initial Hypoglycemic treatment" (MARCH) trial and calculated their hepatic insulin resistance indexes (HIRI). We equally grouped the subjects into tertiles: low, medium, and high HIRI groups based on baseline HIRI; Low, medium, and high ΔHIRI groups based on the decreasing extent of HIRI after a 48-week metformin treatment., Results: Multiple linear regression showed that baseline HIRI was positively associated with the rising degree of Matsuda index and the falling range of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HIRI. Furthermore, baseline fasting insulin, homeostatic model assessment of β cell function (HOMA-β), HOMA-IR, and HIRI were positively associated with the decreasing extent of HIRI, while baseline Matsuda index had a negative association with the falling extent of HIRI., Conclusions: Patients with higher levels of hepatic IR obtained better curative effects from metformin in terms of glycemic control, insulin saving, insulin sensitivity enhancement, and IR improvement. Higher fasting blood glucose, fasting insulin, HOMA-β, IR, and lower Matsuda index were indicators of better hepatic IR improvement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Type 2 diabetes mellitus (T2DM) is common and increasing in prevalence worldwide, with devastating public health consequences. While peripheral insulin resistance is a key feature of most forms of T2DM and has been investigated for over a century, research on brain insulin resistance (BIR) has more recently been developed, including in the context of T2DM and non-diabetes states. Recent data support the presence of BIR in the aging brain, even in non-diabetes states, and found that BIR may be a feature in Alzheimer's disease (AD) and contributes to cognitive impairment. Further, therapies used to treat T2DM are now being investigated in the context of AD treatment and prevention, including insulin. In this review, we offer a definition of BIR, and present evidence for BIR in AD; we discuss the expression, function, and activation of the insulin receptor (INSR) in the brain; how BIR could develop; tools to study BIR; how BIR correlates with current AD hallmarks; and regional/cellular involvement of BIR. We close with a discussion on resilience to both BIR and AD, how current tools can be improved to better understand BIR, and future avenues for research. Overall, this review and position paper highlights BIR as a plausible therapeutic target for the prevention of cognitive decline and dementia due to AD.

In insulin dysregulation, hyperinsulinemia (HI) can be accompanied by peripheral insulin resistance (IR) in horses, which can be diagnosed with an insulin-tolerance test (ITT). The administration of 0.1 IU/kg body weight of recombinant regular human insulin (RHI) should elicit a 50 % reduction of the initial blood glucose concentration at 30 min after insulin administration in insulin sensitive horses. Compared to RHI, porcine zinc insulin (PZI) is veterinary-approved and therefore easier accessible for many practitioners. The aim of this study was to compare the insulin and glucose dynamics during a standard ITT with RHI to an ITT performed with PZI. Twelve Icelandic horses were subjected to an ITT with RHI (ITT-RHI) and with PZI (ITT-PZI) at same dosages in a randomised crossover design. The insulin and glucose dynamics that resulted from these tests were compared, and the consistency of classification into insulin-sensitive and IR categories was evaluated. No complications were observed with the use of either RHI or PZI in ITT. A good correlation of the test results was observed (r = 0.88; P < 0.001). The blood glucose concentrations and the percentage reduction in glucose concentration did not differ significantly between the two tests (P = 0.053), but four out of twelve horses were classified as IR in the ITT-RHI whereas with the ITT-PZI seven out of twelve horses were classified as IR with the 50 % glucose reduction from baseline. Based on the Youden index, when using the ITT-PZI, an adjusted cut-off value for blood glucose reduction of 40 % at 30 min resulted in better test performance. With consideration for the seemingly weaker effect of PZI and the adjusted cut-off value, PZI can be an appropriate substitute to RHI in an ITT., Competing Interests: Conflict of interest statement Tobias Warnken is employed by Boehringer Ingelheim Vetmedica GmbH. None of the authors has any other financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mitochondria facilitate thousands of biochemical reactions, covering a broad spectrum of anabolic and catabolic processes. Here we demonstrate that the adipocyte mitochondrial proteome is markedly altered across multiple models of insulin resistance and reveal a consistent decrease in the level of the mitochondrial processing peptidase miPEP., Objective: To determine the role of miPEP in insulin resistance., Methods: To experimentally test this observation, we generated adipocyte-specific miPEP knockout mice to interrogate its role in the aetiology of insulin resistance., Results: We observed a strong phenotype characterised by enhanced insulin sensitivity and reduced adiposity, despite normal food intake and physical activity. Strikingly, these phenotypes vanished when mice were housed at thermoneutrality, suggesting that metabolic protection conferred by miPEP deletion hinges upon a thermoregulatory process. Tissue specific analysis of miPEP deficient mice revealed an increment in muscle metabolism, and upregulation of the protein FBP2 that is involved in ATP hydrolysis in the gluconeogenic pathway., Conclusion: These findings suggest that miPEP deletion initiates a compensatory increase in skeletal muscle metabolism acting as a protective mechanism against diet-induced obesity and insulin resistance., Competing Interests: Declaration of competing interest The authors declare that there are no competing financial interests that could have influenced the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Maternal hypoxia is strongly linked to insulin resistance (IR) in adult offspring, and altered insulin signaling for muscle glucose uptake is thought to play a central role. However, whether the SIRT3/GSK-3β/GLUT4 axis is involved in maternal hypoxia-induced skeletal muscle IR in old male rat offspring has not been investigated. Maternal hypoxia was established from Days 5 to 21 of pregnancy by continuous infusion of nitrogen and air. The biochemical parameters and levels of key insulin signaling molecules of old male rat offspring were determined through a series of experiments. Compared to the control (Ctrl) old male rat offspring group, the hypoxic (HY) group exhibited elevated fasting blood glucose (FBG) (∼30%), fasting blood insulin (FBI) (∼35%), total triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), as well as results showing impairment in the glucose tolerance test (GTT) and insulin tolerance test (ITT). In addition, hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) revealed impaired cellular structures and mitochondria in the longitudinal sections of skeletal muscle from HY group mice, which might be associated with decreased SIRT3 expression. Furthermore, the expression of insulin signaling molecules, such as GSK-3β and GLUT4, was also altered. In conclusion, the present results indicate that the SIRT3/GSK-3β/GLUT4 axis might be involved in maternal hypoxia-induced skeletal muscle IR in old male rat offspring., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhang pengjie reports was provided by First Affiliated Hospital of Soochow University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The aim is to provide new insights for researchers studying the pathogenesis of diabetic cognitive dysfunction and promoting the wider use of natural products in their treatment. Method: First, the Web of Science Core Collection was selected as the data source for a computerized literature search on oxidative stress and diabetic cognitive dysfunction (DCD). Next, Biblimetrix and VOSviewer performed statistical analysis focusing on publication countries, institutions, authors, research hotspots, and emerging directions in the field. Then, through the analysis of keywords and key articles, the forefront of the field is identified. Finally, we discussed the pathogenesis of DCD, the influence of oxidative stress on DCD and the antioxidant effect of natural products on DCD. Result: 293 valid papers were obtained. Bibliometrics showed that oxidative stress, diabetes, Alzheimer's disease (AD), cognitive decline, insulin resistance and quercetin were the key words of the symbiotic network. Conclusion: The antioxidant effects of natural products in improving DCD have been extensively studied in preclinical studies, providing potential for their treatment in DCD, but their evaluation in clinical trials is currently uncommon. [ABSTRACT FROM AUTHOR]

Introduction and purpose: The topic of apple cider vinegar supplementation and insulin resistance is becoming increasingly widespread, especially on the internet, which carries many potential risks. There is a need to understand both how apple cider vinegar reduces insulin resistance and improves metabolic parameters, as well as the potential risks of its use. Material and methods: Medical databases like PubMed, Google Scholar, and Embase were searched for scientific papers on the safety, benefits, mechanisms, and risks of apple cider vinegar in insulin resistance and related conditions. These were analyzed and summarized in a single review. State of knowledge: Apple cider vinegar supplementation contributes to a reduction in insulin resistance, which is reflected in parameters such as decreased postprandial insulin secretion, lower levels of triglycerides (TG) and total cholesterol (TC), reduced fasting glucose, lower HbA1c levels, and supports weight loss, potentially improving insulin sensitivity. In most cases, no adverse effects or serious side effects were observed with doses of 15-30 ml per day. However, potential risks include delayed gastric emptying, exacerbation of gastroesophageal reflux disease (GERD), gastrointestinal disturbances, tooth erosion, although one study suggests that such supplementation may be associated with acute pancreatitis. Conclusions: More research is needed on supplementation, particularly regarding its duration. Another risk is the search for health information online without critically evaluating the content. Weight loss through a proper diet and exercise appears to be key for improving insulin sensitivity, but supplementation may help achieve results in certain patient groups. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is characterized by over 5% hepatic fat accumulation without secondary causes. The prevalence of NAFLD has escalated in recent years due to shifts in dietary patterns and socioeconomic status, making it the most prevalent chronic liver disease and a significant public health concern globally. Serum uric acid (SUA) serves as the end product of purine metabolism in the body and is intricately linked to metabolic syndrome. Elevated SUA levels have been identified as an independent risk factor for the incidence and progression of NAFLD. This paper reviews the relationship between SUA and NAFLD, the underlying mechanisms of SUA involved in NAFLD, and the potential benefits of SUA-lowering therapy in treating NAFLD. The aim is to raise awareness of SUA management in patients with NAFLD, and to encourage further investigation into pharmacological interventions in this area. [ABSTRACT FROM AUTHOR]

A generally accepted definition of insulin resistance and a consistent treatment strategy for insulin-resistant patients are currently not available in the literature. The HSGE Insulin resistance Working Group created its own definition, diagnostic criteria and therapeutic recommendation based on gynecological symptoms, infertility diagnostics and therapy. Our aim was to formulate a symptom-oriented diagnostic and therapeutic recommendation for Hungarian infertility specialists and practicing gynecologists, which would also facilitate the standard implementation of research in this field. In our position paper, we articulate the doubts about insulin measurement, at the same time we set out the conditions for the standard measurement and we also express the limitations of our own recommendation: the treatment of gynecological symptoms and infertility requires a more precise balance of sugar-insulin metabolism, gynecological symptoms are often among the first to reveal and they cannot be solved without regulating metabolism. In our therapeutic proposal, we describe the optimal diet, exercise program, the use of dietary supplements and drugs and the therapeutic target values, which must be followed closely, especially in the case of infertility treatments. Furthermore, it is important to note that treatment of asymptomatic patients based solely on laboratory parameters is not necessary - only in case of symptomatic, complaining and infertile patients. In order to solve their problems, a comprehensive approach that incorporates a range of therapeutic tools is essential; i.e., in more severe cases, immediate combined therapy might also be necessary compared to the step-by-step therapy setting. [ABSTRACT FROM AUTHOR]

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Ethnopharmacological relevance: Natural substance geraniol has anti-inflammatory and antioxidant qualities. It may be used to treat metabolic diseases such as diabetes, obesity, and cardiovascular illnesses. Innovations in nanoformulations enhance geraniol's absorption, stability, and targeted distribution, augmenting its therapeutic effectiveness and mitigating side effects, despite the limits of traditional treatment. Aim of the review: The therapeutic potential of geraniol in the management of metabolic disorders such as diabetes, obesity, neuroinflammation, and cardiovascular disease is examined in this review. It highlights the anti-inflammatory, antioxidant, and lipid-lowering qualities of geraniol as well as the potential for nanoformulations to increase bioavailability and therapeutic efficacy. Materials and methods: A collection of pertinent research articles about the potential of geraniol in metabolic illnesses, including obesity, type 2 diabetes, as well as cardiovascular diseases, was compiled from PubMed, Scopus, and Google Scholar. Terms such as "metabolic syndrome," "antioxidant," "anti-inflammatory," "geraniol," and "nanoformulations" were employed. Google Patents were also examined in order to offer insights into current and upcoming research. Results: The potential of geraniol to treat metabolic disorders, including obesity, diabetes, hyperlipidemia, and cardiovascular illnesses, is thoroughly reviewed in this article. Recent research has demonstrated the lipid-lowering, antioxidant, and anti-inflammatory properties of geraniol as well as its ability to improve endothelial function and reduce oxidative stress in preclinical animals. The paper delves into the various nanoformulations, including liposomes, nanoparticles, and nanoemulsions, which enhance geraniol's therapeutic efficacy and bioavailability, making it a viable option for managing metabolic syndrome. Conclusion: The antioxidant, anti-inflammatory, and lipid-lowering qualities of geraniol make it a promising treatment for metabolic diseases. Its bioavailability along with therapeutic efficacy are increased by nanoformulations, which makes it a compelling option for the treatment of conditions such as neuroinflammation, diabetes, and obesity. [ABSTRACT FROM AUTHOR]

Microplastics and nanoplastics (M-NPs) are widespread pollutants in the environment, posing growing risks to human health and garnering increasing concern from researchers. Due to their small particle size, ease of adsorption, and resistance to degradation, M-NPs can retain and migrate in the environment for long-term periods. Upon entering organisms, M-NPs have been reported to cause inflammation and oxidative stress and result in abnormalities in glycolipid metabolism. Furthermore, research suggests that exposure to M-NPs may act as a causative agent for metabolic and cardiovascular diseases such as diabetes, obesity, and atherosclerosis. This paper aims to review the consequences of exposure to M-NPs on animal and cellular glycolipid metabolism and discusses the disruption of gut microbial homeostasis and the subsequent emergence of insulin resistance. PPAR signaling pathway activation after exposure to M-NPs was found to lead to increased hepatic fat accumulation and impaired lipid metabolism. Additionally, the paper highlights how M-NPs exacerbate the progression of obesity and diabetes in patients, induce damage to vascular endothelial cells, trigger oxidative stress, and contribute to the development of atherosclerosis. Despite the growing concern, the toxicity and molecular mechanism of M-NPs on glycolipid metabolism remain understudied, and effective methods for removing plastic pollutants deposited in the body are yet to be established. These findings provide valuable insights for future research in this field. [ABSTRACT FROM AUTHOR]

The article presents several research papers related to sleep. One paper discusses central sleep apnea (CSA), which is common among pre-term infants, in adults at altitude, and in patients with congestive heart failure (CHF). Another study is on the relationship between Obstructive Sleep Apnoea (OSA) and cardiovascular and metabolic disorders, such as insulin resistance and diabetes. Another study is on memory and sleeping problems during pregnancy.

Aims: Psychological insulin resistance is a common barrier to initiation and persistence with insulin therapy that affects approximately 42.7% of people living with type II diabetes mellitus, which may negatively impact self‐management. This study aimed to assess patients' levels of psychological insulin resistance and to identify factors associated with self‐management in patients with type II diabetes mellitus treated with insulin therapy. Methods: We adopted a cross‐sectional design. Subjects from the metabolism and endocrinology outpatient departments of a regional teaching hospital in central Taiwan were recruited by consecutive sampling. Patients were assessed for psychological insulin resistance and self‐management using the barriers to insulin treatment questionnaire and the partners in health scale. Results: A total of 222 patients with type II diabetes mellitus were recruited. Patients had an average psychological insulin resistance score of 3.14 (maximum of 8). Positive self‐management was associated with insulin therapy injection by patient, fewer expectations regarding positive insulin‐related outcomes, no diabetes‐related complications, less fear of injection and self‐testing, no hypoglycaemia within the previous year, and younger age. Conclusion: Insulin therapy injection by patient and no diabetes‐related complications were the most common factors associated with overall self‐management and with each domain of self‐management in patients with type II diabetes mellitus treated with insulin therapy. Insulin therapy education should be offered to improve patients' beliefs about insulin therapy and enhance patients' ability to perform self‐management. Summary statement: What is already known about this topic? Psychological insulin resistance is a common psychological barrier to initiation and persistence with insulin therapy.Psychological insulin resistance causes poor glycaemic control and diabetes‐related complications.Psychological insulin resistance may negatively impact self‐management in patients with type II diabetes mellitus. What is the contribution of this paper? Positive self‐management was associated with insulin therapy injection by patient, fewer expectations regarding positive insulin‐related outcomes, no diabetes‐related complications, less fear of injection and self‐testing, no hypoglycaemia within the previous year, and younger age.Insulin therapy injection by patient and no diabetes‐related complications were the most common factors associated with overall self‐management and with each domain of self‐management in patients with type II diabetes mellitus treated with insulin therapy.Patients with poor self‐management had statistically significantly higher levels of overall psychological insulin resistance, fear of injections and self‐testing, expectations regarding positive insulin‐related outcomes, and stigmatization by insulin injections, compared to those with appropriate self‐management. What are the implications of this paper? Knowing in advance the factors associated with diabetes self‐management will allow healthcare professionals prevent psychological insulin resistance in patients with type II diabetes mellitus treated with insulin therapy.Healthcare professionals can design and provide patient‐centred diabetes education based on education level to enhance self‐management. [ABSTRACT FROM AUTHOR]

Simple Summary: Metformin is one of the most widely used drugs in the world, since its first use in the second part of the 1950s in France (Aron, 1957) and in the United Kingdom (Rona, 1958), and is on the World Health Organization's List of Essential Medicines. Traditionally, metformin is used in diabetes mellitus, mainly in overweight and obese subjects, but also in other conditions of impaired glucose metabolism, such as insulin resistance. In recent years, in vitro and in vivo data on this molecule as an antiproliferative modulator have suggested a series of clinical trials in several tumors that—at the moment—have not confirmed the expected positive results. The aim of this paper is to offer a double vision of this molecule, with a very light side about the metabolic aspects and a darker side concerning its antineoplastic activity, focusing on molecular and subcellular pathways involved in both fields and discussing the contrast between preliminary cellular data and real clinical outcomes in different neoplasms. The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open? [ABSTRACT FROM AUTHOR]

Simple Summary: Obesity is a global concern within human, pet, and horse populations. A major consequence of obesity is a disruption to glucose and insulin metabolisms, leading to metabolic conditions including insulin resistance and/or diabetes. This paper discusses these consequences of obesity and excess adipose tissue both in idle and athletic subjects. Exercise conditioning can improve glucose metabolism and insulin sensitivity. Regular exercise can also facilitate weight loss, wherein the reduction of adipose tissue alleviates fat's negative impacts on metabolism, while also decreasing the mechanical load on a subject's limbs. These actions could result in better health, reduced incidence of metabolic disease, and, perhaps, improved performance. Obesity is an important health concern in horses, along with humans and companion animals. Adipose tissue is an inflammatory organ that alters the insulin-signaling cascade, ultimately causing insulin dysregulation and impaired glucose metabolism. These disruptions can increase the risk of metabolic disease and laminitis in horses and may also impact energy metabolism during exercise. A single bout of exercise, along with chronic exercise conditioning, increases insulin sensitivity and glucose disposal via both contraction- and insulin-mediated glucose uptake pathways. Regular exercise also increases calorie expenditure, which can facilitate weight (as body fat) loss. This paper explores the metabolic pathways affected by adiposity, as well as discusses the impact of exercise on insulin metabolism in horses. [ABSTRACT FROM AUTHOR]

The article presents abstracts on equine veterinary which includes the insulin sensitivity from dexamethasone, the equine midge-borne disease in Great Britain, and the surgical treatment for cryptorchidism among horses.

Purpose: The purpose of this meta-analysis was to examine the effect of pomegranate juice (PJ) intake on glycemic control in adults. Design/methodology/approach: Materials and methods: PubMed (Medline), ISI Web of Science, Cochrane Library and Scopus databases, measuring glucose and/or insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in adults, were searched from inception to December 11, 2021. Moreover, to examine whether grouping factors influenced heterogeneity between research results, subgroup analysis was used. Findings: This meta-analysis showed that PJ intake reduced HOMA-IR significantly, especially if =250 mL was used. This reducing effect remained significant in females, nondiabetic patients and unhealthy subjects. Originality/value: The authors believe the presented data would be highly motivating and of a wide readership for the readers of your journal, and this paper stimulating a surge of research on the impact of PJ consumption on glycemic indices. [ABSTRACT FROM AUTHOR]