Exacerbated Insulin Resistance Research Articles

Obesity and Adipose-Derived Extracellular Vesicles: Implications for Metabolic Regulation and Disease

Obesity, a global epidemic, is a major risk factor for chronic diseases such as type 2 diabetes, cardiovascular disorders, and metabolic syndrome. Adipose tissue, once viewed as a passive fat storage site, is now recognized as an active endocrine organ involved in metabolic regulation and inflammation. In obesity, adipose tissue dysfunction disrupts metabolic balance, leading to insulin resistance and increased production of adipose-derived extracellular vesicles (AdEVs). These vesicles play a key role in intercellular communication and contribute to metabolic dysregulation, affecting organs such as the heart, liver, and brain. AdEVs carry bioactive molecules, including microRNAs, which influence inflammation, insulin sensitivity, and tissue remodeling. In the cardiovascular system, AdEVs can promote atherosclerosis and vascular dysfunction, while those derived from brown adipose tissue offer cardioprotective effects. In type 2 diabetes, AdEVs exacerbate insulin resistance and contribute to complications such as diabetic cardiomyopathy and cognitive decline. Additionally, AdEVs are implicated in metabolic liver diseases, including fatty liver disease, by transferring inflammatory molecules and lipotoxic microRNAs to hepatocytes. These findings highlight the role of AdEVs in obesity-related metabolic disorders and their promise as therapeutic targets for related diseases.

Obesity and Polycystic Ovary Syndrome.

The core pathophysiology of polycystic ovary syndrome involves an overproduction of androgens primarily originating from ovarian thecal cells. Two major external triggers promote androgen overproduction in the ovaries: the increased secretion of luteinizing hormone, a consequence of aberrant hypothalamic gonadotropin-releasing hormone secretion dynamics, and compensatory hyperinsulinemia resulting from insulin resistance. Obesity interacts with polycystic ovary syndrome in multiple ways, but a major role of obesity in its pathophysiology is the exacerbation of insulin resistance. Additionally, obesity contributes to polycystic ovary syndrome by facilitating the conversion of precursor hormones to testosterone within adipose cells. Moreover, obesity can lead to relative hyperandrogenemia, which is marked by lower levels of sex hormone binding globulin and increased availability of free testosterone to target tissues. Also, obesity affects the secretion of gonadotropins, resulting in heightened luteinizing hormone secretion or increased sensitivity of thecal cells to luteinizing hormone. Obesity-related insulin resistance might be amplified by alterations in adipokine and inflammatory cytokine production. Ultimately, obesity and polycystic ovary syndrome might share a common genetic predisposition. The cornerstone of managing polycystic ovary syndrome is to address individual symptoms such as hyperandrogenism (hirsutism, acne, and female type boldness), menstrual irregularities, and infertility stemming from anovulation. However, obesity is integral to the pathophysiology of polycystic ovary syndrome and exacerbates all of its features. Therefore, lifestyle modifications aimed at weight reduction should be the primary strategy in overweight or obese women with polycystic ovary syndrome.

Potential shared mechanisms in atopic dermatitis and type 2 diabetes identified via transcriptomic and machine learning approaches

Although atopic dermatitis (AD) and type 2 diabetes mellitus (T2DM) may appear clinically and pathophysiologically unrelated, AD is a common skin disease characterized by chronic inflammation and skin barrier dysfunction, whereas T2DM is a metabolic disorder marked by hyperglycemia and chronic inflammation, which further exacerbates insulin resistance (IR) through the release of systemic inflammatory factors. Despite their apparent differences, the molecular mechanisms shared between AD and T2DM remain relatively unexplored. In this study, we integrated transcriptomic data from both AD and T2DM using differential gene expression analyses (DEGs), gene set variation analysis (GSVA), and machine learning algorithms to uncover common features of these diseases. We identified several characteristic genes, including LTF, LTB4R, and CCR1, which are significantly upregulated in both conditions and may serve as potential biomarkers. Furthermore, virtual screening revealed that Dioscin, Camptothecin, and Albamycin exhibit strong affinity for the CCR1 binding site, indicating their potential as therapeutic candidates. In summary, this study elucidates the shared molecular mechanisms of AD and T2DM and introduces new potential targets and drugs for the diagnosis and treatment of these diseases.

NUTRITIONAL STRATEGIES FOR REDUCING SUGAR-SWEETENED BEVERAGE CONSUMPTION AND PREVENTING METABOLIC DISEASES

Reducing the consumption of sugar-sweetened beverages is crucial for preventing and managing metabolic diseases such as obesity, insulin resistance, and type 2 diabetes. Excessive consumption of sodas and other sweetened beverages is a major risk factor for these conditions, as these drinks contain empty calories, exacerbating insulin resistance and causing harmful glycemic spikes. For patients with prediabetes, implementing effective nutritional strategies to reduce the consumption of these beverages is essential to prevent progression to type 2 diabetes. Nutritional interventions that promote awareness of the risks of sugar-sweetened beverages, offer healthy alternatives such as water and unsweetened teas, and modify the food environment are key to changing eating behaviors and improving metabolic health. Adopting a balanced diet rich in fiber and lean proteins is also important for controlling blood sugar levels and reducing cravings for sugary foods. Furthermore, combining nutritional strategies with regular physical activity can enhance the benefits, as exercise improves insulin sensitivity and contributes to weight management. Widely cited studies highlight the association between sugar-sweetened beverage consumption and an increased risk of type 2 diabetes and other chronic diseases. Public policies that encourage the reduction of sweetened beverage consumption are essential to combat the growing epidemic of metabolic diseases.

Palmitic acid induces insulin resistance and oxidative stress-mediated cell injury through accumulation of lipid rafts in murine hepatocytes.

Lipid rafts are subdomains of the cell membrane that are rich in cholesterol and glycolipids, and they are involved in various cellular processes and pathophysiological mechanisms. However, the specific role of lipid rafts in hepatocyte dysfunction during the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) is not fully understood. In this study, we investigated the impact of lipid rafts on insulin sensitivity and hepatocyte injury induced by saturated free fatty acids (sFFAs) using primary-cultured mouse hepatocytes. Treatment of primary hepatocytes with palmitic acid (PA) resulted in significant lipid droplet accumulation in the cytoplasm and a marked increase in the number of cells with accumulation of lipid raft. The addition of cholesterol oxidase (CHOX), which disrupts lipid rafts, did not affect PA-induced lipid droplet formation, but significantly reduced the number of cells with accumulation of lipid raft. In PA-treated hepatocytes, insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-2 and Akt was markedly decreased, but this effect was alleviated by CHOX. Furthermore, PA-pretreated hepatocytes exhibited substantial increases in reactive oxygen species (ROS) production and cell death when exposed to low doses of tert-butyl hydroperoxide (t-BuOOH). In contrast, treatment with CHOX after PA significantly reduced ROS production and cell death following t-BuOOH. These results suggest that PA-induced accumulation of lipid raft not only exacerbates insulin resistance but also enhances responsiveness to oxidative stress stimuli, contributing to MASLD pathogenesis. Modulation of lipid rafts may represent a promising therapeutic target for MASLD.

Impact of serum carotenoids on cardiovascular mortality risk in middle-aged and elderly adults with metabolic syndrome.

Metabolic syndrome (MetS), characterized by abdominal adiposity, hypertension, hyperglycemia, and dyslipidemia, is associated with dysregulated immune function, elevated oxidative stress, and chronic low-grade inflammation. Aging exacerbates insulin resistance and the prevalence of MetS. Dietary antioxidants, such as carotenoids, may play a role in preventing cardiovascular disease (CVD) mortality, but evidence remains mixed, particularly among middle-aged and elderly individuals with MetS. We analyzed data from 6,601 participants aged 40 years and above with MetS from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 2001-2006 cycles. Serum concentrations of α-carotene, β-carotene, lycopene, β-cryptoxanthin, and combined lutein/zeaxanthin were quantified. Participants were followed for a median of 16.8 years. Cox proportional-hazards models were used to assess the association between serum carotenoid concentrations and CVD mortality risk, with adjustment for potential confounders. During the follow-up period, 1,237 CVD deaths were identified. Analysis revealed an inverse dose-response relationship between serum lycopene levels and cardiovascular mortality risk. Compared to the lowest quartile, the multivariable-adjusted hazard ratios (95% confidence intervals) for ascending quartiles of serum lycopene were 0.84 (0.71, 1.00), 0.87 (0.74, 1.03), and 0.77 (0.61, 0.97), with a significant trend (p = 0.039). No significant associations were observed for other carotenoids. In this prospective cohort study of 40-year-old and older individuals with MetS, we observed an inverse association between serum lycopene levels and CVD mortality risk.

Association between depression and diabetes among American adults using NHANES data from 2005 to 2020

Depression impairs self-management in diabetic patients, exacerbates insulin resistance, and elevates glycated hemoglobin (HbA1c) levels, thereby increasing diabetes risk. This study analyzed data from 30,386 participants in the National Health and Nutrition Examination Survey (NHANES), assessing depression severity using the 9-item Patient Health Questionnaire (PHQ-9) and evaluating diabetes status through clinical markers such as HbA1c, random blood glucose, and fasting blood glucose. Participants were stratified by depression severity and diabetes status to examine the relationship between depression and diabetes risk. We applied descriptive statistics, logistic regression models, subgroup analyses, and restricted cubic spline (RCS) modeling to explore this association. The results revealed that greater depression severity was significantly associated with increased diabetes incidence, elevated HbA1c, fasting glucose, and insulin levels. Multivariate regression analysis confirmed a consistent positive correlation between depression severity and diabetes risk. Subgroup analyses further identified significant relationships between depression and various demographic and behavioral factors, including gender, race, BMI, smoking status, and prediabetic conditions. Additionally, the RCS model demonstrated a clear increase in diabetes risk with rising PHQ-9 scores. In conclusion, our study demonstrates that the severity of depression is positively correlated with the risk of diabetes, and this association may be closely linked to various glycemic and lipid metabolic parameters.

New Onset Diabetes After COVID 19 (NODAC) is predominantly due to exacerbated Insulin Resistance (IR) rather than beta cell dysfunction: Lessons from tertiary care hospital data during confluence of two epidemics.

To investigate determinants of new onset diabetes after COVID-19 (NODAC) and its recovery at 6 months. This was an observational follow up study conducted from August, 2020 to July, 2023, recruiting patients with preexisting DM and COVID 19 patients with no history of DM. Multivariate regression analysis was used to determine the factors responsible for severity of COVID 19 infection in preexisting DM group. Clinical, laboratory and glycometabolic parameters were estimated at baseline and 6 months in NODAC and euglycemic group to determine the factors responsible for NODAC and its persistence at 6 months. Of 1310 patients, 855 (65.3%) COVID 19 patients were further divided based on their glycemic status: preexisting DM (19%), NODAC (8.5%) and euglycemia (72.5%). Older age and male gender were independent risk factors for severe COVID 19 disease in patients with preexisting diabetes. Prevalence of NODAC in present study was 8.5%. Patients with NODAC had higher mean fasting blood glucose (FBG), random blood glucose (RBG) and HbA1c at baseline as compared to COVID with euglycemic group with no difference in serum C-peptide levels. Female gender, family history of DM, signs of insulin resistance, higher BMI, WHR, HbA1c, serum insulin levels, FBG and RBG predicted persistence of NODAC at 6 months. Preexisting DM is a risk factor for severe COVID 19 disease. Patients with NODAC have evidence of persistence insulin resistance on follow up, underscoring the need for long term glycemic monitoring.

Metabolic Dysfunction-Associated Steatotic Liver Disease and Polycystic Ovary Syndrome: A Complex Interplay.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) are prevalent conditions that have been correlated with infertility through overlapped pathophysiological mechanisms. MASLD is associated with metabolic syndrome and is considered among the major causes of chronic liver disease, while PCOS, which is characterized by ovulatory dysfunction and hyperandrogenism, is one of the leading causes of female infertility. The pathophysiological links between PCOS and MASLD have not yet been fully elucidated, with insulin resistance, hyperandrogenemia, obesity, and dyslipidemia being among the key pathways that contribute to liver lipid accumulation, inflammation, and fibrosis, aggravating liver dysfunction. On the other hand, MASLD exacerbates insulin resistance and metabolic dysregulation in women with PCOS, creating a vicious cycle of disease progression. Understanding the intricate relationship between MASLD and PCOS is crucial to improving clinical management, while collaborative efforts between different medical specialties are essential to optimize fertility and liver health outcomes in individuals with MASLD and PCOS. In this review, we summarize the complex interplay between MASLD and PCOS, highlighting the importance of increasing clinical attention to the prevention, diagnosis, and treatment of both entities.

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.

Retinal Diabetopathy? Sleep Disorders, Retinal Changes, and Insulin Resistance: A Synthesized Systematic Review

ABSTRACT Sleep disturbances, particularly prevalent in modern lifestyles, have been increasingly associated with metabolic disorders such as insulin resistance and type 2 diabetes mellitus (DM) (T2DM). Epidemiological evidence underscores the link between impaired sleep and elevated risks of cardiovascular diseases and mortality rates, alongside the emergence of metabolic dysregulation. Notably, conditions such as obstructive sleep apnea syndrome contribute to disrupted sleep architecture and exacerbate insulin resistance through repeated drops in blood oxygen levels during sleep. Furthermore, chronic sleep deprivation, irregular sleep schedules, and shift work disrupt circadian rhythms, amplifying the risk of metabolic disorders. A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for articles from January 2010 to October 2023 using terms such as “sleep disturbances,” “Type 2 Diabetes Mellitus,” and “retinal receptors.” Inclusion criteria covered studies on human and animal participants, comparative analyses, and reviews. Exclusion criteria ruled out nonpeer-reviewed works and those with limited population sizes. Data extraction focused on study design, populations, types of sleep disorders, metabolic effects, and retinal health impacts. Results emphasized the bidirectional relationship among these variables. The critical analytical research and review highlights the bidirectional relationship between retinal receptor dysfunction and DM, emphasizing how metabolic disturbances associated with diabetes impact retinal health, while dysfunctional retinal receptors contribute to the progression of diabetes-related complications. Insights into the role of insulin receptors in the retina and the blood–retinal barrier underscore the mechanisms through which insulin resistance compromises retinal integrity, leading to neuroinflammation, oxidative stress, and photoreceptor damage. The disturbed sleep can also affect the melatonin secretion, thereby affecting insulin resistance. We preliminarily have named the nexus as retinal diabetopathy. By elucidating the impact of intermittent hypoxia and sleep fragmentation on cellular signaling and metabolism, particularly in vital organs such as muscles, liver, fat, and pancreas, the article provides a comprehensive understanding of how prevalent sleep disturbances and retinal changes contribute to the development and progression of T2DM. Overall, this research underscores the importance of addressing sleep disorders in the prevention and management of metabolic disorders.

Research progress of traditional Chinese medicines and active ingredients targeting M1/M2 macrophage polarization balance in intervening obese with type 2 diabetes

Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.

Growth hormone therapy in Turner Syndrome (TS): A focused review on glucose metabolism outcomes

Introduction: Turner Syndrome (TS) patients inherently possess a higher risk of developing glycemic abnormalities due to their unique genetic makeup, and the administration of growth hormone (GH) therapy, while beneficial for growth, might exacerbate this tendency towards disturbed glucose metabolism. Objective of the Review: To evaluate the existing literature on the effects of GH therapy on glucose metabolism in TS patients, highlighting the balance between therapeutic benefits and potential metabolic risks. Methods: This review scrutinizes studies published from 2000 to 2024, focusing on the outcomes related to glucose metabolism in TS individuals undergoing GH therapy, encompassing aspects like insulin sensitivity, glucose tolerance, and metabolic health. Results: Insulin Sensitivity and Resistance: Initial findings suggest that GH therapy may exacerbate insulin resistance and elevate insulin levels, although these effects appear transient and potentially reversible after the cessation of therapy. Long-term Metabolic Outcomes: Later studies indicate that long-term GH therapy may lead to an improvement in insulin sensitivity and a normalization of carbohydrate metabolism, particularly after the therapy is discontinued. Variable Impacts on Glucose Tolerance: The reviewed literature shows mixed effects on glucose tolerance, with some studies reporting no significant changes, while others highlight a potential risk for worsening glucose metabolism. Body Composition and Metabolic Profile: Positive changes in body composition and lipid profiles were noted, which could confer metabolic benefits, yet the therapy's role in increasing insulin levels warrants careful consideration. Individual Variability and Monitoring Needs: The diverse responses to GH therapy underscore the necessity for individualized treatment plans and diligent metabolic monitoring to mitigate potential risks and optimize therapeutic outcomes. Conclusion: The administration of GH therapy in TS requires a delicate balance, considering its potential to both benefit and pose risks to glucose metabolism. Tailored monitoring and a comprehensive understanding of the individual patient’s metabolic response are essential for maximizing the therapy's efficacy while minimizing associated metabolic complications.

Intramuscular diacylglycerol accumulates with acute hyperinsulinemia in insulin-resistant phenotypes.

Elevated skeletal muscle diacylglycerols (DAGs) and ceramides can impair insulin signaling, and acylcarnitines (acylCNs) reflect impaired mitochondrial fatty acid oxidation, thus, the intramuscular lipid profile is indicative of insulin resistance. Acute (i.e., postprandial) hyperinsulinemia has been shown to elevate lipid concentrations in healthy muscle and is an independent risk factor for type 2 diabetes (T2D). However, it is unclear how the relationship between acute hyperinsulinemia and the muscle lipidome interacts across metabolic phenotypes, thus contributing to or exacerbating insulin resistance. We therefore investigated the impact of acute hyperinsulinemia on the skeletal muscle lipid profile to help characterize the physiological basis in which hyperinsulinemia elevates T2D risk. In a cross-sectional comparison, endurance athletes (n = 12), sedentary lean adults (n = 12), and individuals with obesity (n = 13) and T2D (n = 7) underwent a hyperinsulinemic-euglycemic clamp with muscle biopsies. Although there were no significant differences in total 1,2-DAG fluctuations, there was a 2% decrease in athletes versus a 53% increase in T2D during acute hyperinsulinemia (P = 0.087). Moreover, C18 1,2-DAG species increased during the clamp with T2D only, which negatively correlated with insulin sensitivity (P < 0.050). Basal muscle C18:0 total ceramides were elevated with T2D (P = 0.029), but not altered by clamp. Acylcarnitines were universally lowered during hyperinsulinemia, with more robust reductions of 80% in athletes compared with only 46% with T2D (albeit not statistically significant, main effect of group, P = 0.624). Similar fluctuations with acute hyperinsulinemia increasing 1,2 DAGs in insulin-resistant phenotypes and universally lowering acylcarnitines were observed in male mice. In conclusion, acute hyperinsulinemia elevates muscle 1,2-DAG levels with insulin-resistant phenotypes. This suggests a possible dysregulation of intramuscular lipid metabolism in the fed state in individuals with low insulin sensitivity, which may exacerbate insulin resistance.NEW & NOTEWORTHY Postprandial hyperinsulinemia is a risk factor for type 2 diabetes and may increase muscle lipids. However, it is unclear how the relationship between acute hyperinsulinemia and the muscle lipidome interacts across metabolic phenotypes, thus contributing to insulin resistance. We observed that acute hyperinsulinemia elevates muscle 1,2-DAGs in insulin-resistant phenotypes, whereas ceramides were unaltered. Insulin-mediated acylcarnitine reductions are also hindered with high-fat feeding. The postprandial period may exacerbate insulin resistance in metabolically unhealthy phenotypes.

Positive Effects of Physical Activity on Insulin Signaling.

Physical activity is integral to metabolic health, particularly in addressing insulin resistance and related disorders such as type 2 diabetes mellitus (T2DM). Studies consistently demonstrate a strong association between physical activity levels and insulin sensitivity. Regular exercise interventions were shown to significantly improve glycemic control, highlighting exercise as a recommended therapeutic strategy for reducing insulin resistance. Physical inactivity is closely linked to islet cell insufficiency, exacerbating insulin resistance through various pathways including ER stress, mitochondrial dysfunction, oxidative stress, and inflammation. Conversely, physical training and exercise preserve and restore islet function, enhancing peripheral insulin sensitivity. Exercise interventions stimulate β-cell proliferation through increased circulating levels of growth factors, further emphasizing its role in maintaining pancreatic health and glucose metabolism. Furthermore, sedentary lifestyles contribute to elevated oxidative stress levels and ceramide production, impairing insulin signaling and glucose metabolism. Regular exercise induces anti-inflammatory responses, enhances antioxidant defenses, and promotes mitochondrial function, thereby improving insulin sensitivity and metabolic efficiency. Encouraging individuals to adopt active lifestyles and engage in regular exercise is crucial for preventing and managing insulin resistance and related metabolic disorders, ultimately promoting overall health and well-being.

Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance

Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.

Gestational and Postpartum Exposure to PM2.5 Components and Glucose Metabolism in Chinese Women: A Prospective Cohort Study.

Pregnant women are physiologically prone to glucose intolerance, while the puerperium represents a critical phase for recovery. However, how air pollution disrupts glucose homeostasis during the gestational and early postpartum periods remains unclear. This prospective cohort study conducted an oral glucose tolerance test and measured the insulin levels of 834 pregnant women in Guangzhou, with a follow-up for 443 puerperae at 6-8 weeks postpartum. Residential PM2.5 and five chemical components were estimated by an established spatiotemporal model. The adjusted linear model showed that an IQR increase in gestational PM2.5 exposure was associated with an increase of 0.17 mmol/L (95% CI: 0.06, 0.28) in fasting plasma glucose (FPG) and 0.24 (95% CI: 0.05, 0.42) in the insulin resistance index. Postpartum PM2.5 exposure was linked to a 0.17 mmol/L (95% CI: 0.05, 0.28) elevation in FPG per IQR, with a strengthened association found in women with gestational diabetes (Pinteraction = 0.003). In the quantile-based g-computation model, NO3- consistently contributed to the combined effect of PM2.5 components on gestational and postpartum FPG. This study was the first to suggest that PM2.5 components were associated with exacerbated gestational insulin resistance and elevated postpartum FPG. Targeted interventions reducing the emissions of toxic PM2.5 components are essential to improving maternal glucose metabolism.

Prolyl isomerase Pin1 in skeletal muscles contributes to systemic energy metabolism and exercise capacity through regulating SERCA activity

The skeletal muscle is a pivotal organ involved in the regulation of both energy metabolism and exercise capacity. There is no doubt that exercise contributes to a healthy life through the consumption of excessive energy or the release of myokines. Skeletal muscles exhibit insulin sensitivity and can rapidly uptake blood glucose. In addition, they can undergo non-shivering thermogenesis through actions of both the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) and small peptide, sarcolipin, resulting in systemic energy metabolism. Accordingly, the maintenance of skeletal muscles is important for both metabolism and exercise. Prolyl isomerase Pin1 is an enzyme that converts the cis-trans form of proline residues and controls substrate function. We have previously reported that Pin1 plays important roles in insulin release, thermogenesis, and lipolysis. However, the roles of Pin1 in skeletal muscles remains unknown. To clarify this issue, we generated skeletal muscle-specific Pin1 knockout mice.Pin1 deficiency had no effects on muscle weights, morphology and ratio of fiber types. However, they showed exacerbated obesity or insulin resistance when fed with a high-fat diet. They also showed a lower ability to exercise than wild type mice did. We also found that Pin1 interacted with SERCA and elevated its activity, resulting in the upregulation of oxygen consumption. Overall, our study reveals that Pin1 in skeletal muscles contributes to both systemic energy metabolism and exercise capacity.

The Reduced Gut Lachnospira Species Is Linked to Liver Enzyme Elevation and Insulin Resistance in Pediatric Fatty Liver Disease.

The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver disease (MAFLD). This study included 105 children and utilized anthropometric measurements, blood tests, the Ultrasound Fatty Liver Index, and fecal DNA sequencing to assess the relationship between gut microbiota and pediatric MAFLD. Notable decreases in Lachnospira spp., Faecalibacterium spp., Oscillospira spp., and Akkermansia spp. were found in the MAFLD group. Lachnospira spp. was particularly reduced in children with MAFLD and hepatitis compared to controls. Both MAFLD groups showed a reduction in flavone and flavonol biosynthesis sequences. Lachnospira spp. correlated positively with flavone and flavonol biosynthesis and negatively with insulin levels and insulin resistance. Body weight, body mass index (BMI), and total cholesterol levels were inversely correlated with flavone and flavonol biosynthesis. Reduced Lachnospira spp. in children with MAFLD may exacerbate insulin resistance and inflammation through reduced flavone and flavonol biosynthesis, offering potential therapeutic targets.

Unveiling Anti-Diabetic Potential of Baicalin and Baicalein from Baikal Skullcap: LC-MS, In Silico, and In Vitro Studies.

Type 2 diabetes mellitus (T2DM) is marked by persistent hyperglycemia, insulin resistance, and pancreatic β-cell dysfunction, imposing substantial health burdens and elevating the risk of systemic complications and cardiovascular diseases. While the pathogenesis of diabetes remains elusive, a cyclical relationship between insulin resistance and inflammation is acknowledged, wherein inflammation exacerbates insulin resistance, perpetuating a deleterious cycle. Consequently, anti-inflammatory interventions offer a therapeutic avenue for T2DM management. In this study, a herb called Baikal skullcap, renowned for its repertoire of bioactive compounds with anti-inflammatory potential, is posited as a promising source for novel T2DM therapeutic strategies. Our study probed the anti-diabetic properties of compounds from Baikal skullcap via network pharmacology, molecular docking, and cellular assays, concentrating on their dual modulatory effects on diabetes through Protein Tyrosine Phosphatase 1B (PTP1B) enzyme inhibition and anti-inflammatory actions. We identified the major compounds in Baikal skullcap using liquid chromatography-mass spectrometry (LC-MS), highlighting six flavonoids, including the well-studied baicalein, as potent inhibitors of PTP1B. Furthermore, cellular experiments revealed that baicalin and baicalein exhibited enhanced anti-inflammatory responses compared to the active constituents of licorice, a known anti-inflammatory agent in TCM. Our findings confirmed that baicalin and baicalein mitigate diabetes via two distinct pathways: PTP1B inhibition and anti-inflammatory effects. Additionally, we have identified six flavonoid molecules with substantial potential for drug development, thereby augmenting the T2DM pharmacotherapeutic arsenal and promoting the integration of herb-derived treatments into modern pharmacology.