Objectives: Insulin resistance (IR) has been shown to play important role in the pathogenesis of type 2 diabetes mellitus (T2DM). There is an intricate interplay between IR, dyslipidemia, and serum uric acid (SUA) in people with and without diabetes. Physical activity has a positive impact on insulin sensitivity in insulin-resistant populations. However, the effect of different intensities of physical activity on insulin levels under different lipid indices and SUA levels is unclear.Methods: To explore the association between physical activity and insulin, we enrolled 12,982 participants aged above 18 years from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2018. Next, we conducted multivariate logistic regression analyses, generated fitted smoothing curves, and visualized the data using generalized additive models.Results: Increased intensities of physical activity can significantly reduce insulin levels. The association between physical activity and insulin persisted even after adjusting for confounding factors, with β value (95% CI) = −17.10 (−21.64, −12.56) in moderate group, β value (95% CI) = −28.60 (−33.08, −24.11) in high group, respectively. High-intensity physical activity significantly lowered insulin levels in the lower and higher SUA tertiles, and three tertiles of LDL-c, HDL-c, and TG. Moreover, the link between physical activity and insulin was stronger in male individuals.Conclusion: This study shows that physical activity can significantly lower insulin levels, and high-intensity physical activity still has additional potential benefits for insulin levels, even in the condition of dyslipidemia and hyperuricemia.

Patients with cancer who receive doxorubicin (DOX) treatment can experience cardiac dysfunction, which can finally develop into heart failure. Oxidative stress is considered the most important mechanism for DOX-mediated cardiotoxicity. Rutaecarpine (Rut), a quinazolinocarboline alkaloid extracted from Evodia rutaecarpa was shown to have a protective effect on cardiac disease. The purpose of this study is to investigate the role of Rut in DOX-induced cardiotoxicity and explore the underlying mechanism. Intravenous injection of DOX (5 mg/kg, once a week) in mice for 4 weeks was used to establish the cardiotoxic model. Echocardiography and pathological staining analysis were used to detect the changes in structure and function in the heart. Western blot and real-time PCR analysis were used to detect the molecular changes. In this study, we found that DOX time-dependently decreased cardiac function with few systemic side effects. Rut inhibited DOX-induced cardiac fibrosis, reduction in heart size, and decrease in heart function. DOX-induced reduction in superoxide dismutase (SOD) and glutathione (GSH), enhancement of malondialdehyde (MDA) was inhibited by Rut administration. Meanwhile, Rut inhibited DOX-induced apoptosis in the heart. Importantly, we further found that Rut activated AKT or nuclear factor erythroid 2-related factor 2 (Nrf-2) which further upregulated the antioxidant enzymes such as heme oxygenase-1 (HO-1) and GSH cysteine ligase modulatory subunit (GCLM) expression. AKT inhibitor (AKTi) partially inhibited Nrf-2, HO-1, and GCLM expression and abolished the protective role of Rut in DOX-induced cardiotoxicity. In conclusion, this study identified Rut as a potential therapeutic agent for treating DOX-induced cardiotoxicity by activating AKT.

The study aims to explore the relationship between plasma insulin secretion and arterial stiffness in nondiabetic essential hypertensive patients. A total of 730 nondiabetic essential hypertensive patients registered between January 2016 and October 2020 were enrolled. A two-hour oral glucose tolerance test (OGTT) was performed to detect the levels of C-peptide and blood glucose at 0 hours and 2 hours, as well as the difference between C-peptide (Δ C-peptide) and blood glucose (Δ blood glucose) over the same period. Patients were divided into two groups: the normal glucose tolerance (NGT) group (n = 322) and the impaired glucose tolerance (IGT) group (n = 408). A multiple linear regression analysis was used to evaluate the association between brachial-ankle pulse wave velocity (baPWV) and the other factors. 0 h C-peptide, 2 h C-peptide, and Δ C-peptide were found to be higher in the IGT group. baPWV was positively linear correlated with 2 h C-peptide (r = 0.086, ) and Δ C-peptide (r = 0.115, ). baPWV remained independently associated with 0 h C-peptide, 2 h C-peptide, and Δ C-peptide, after adjusting by age, gender, smoking, body mass index (BMI), high-density lipoprotein (HDL), cholesterol, systolic blood pressure (SBP), and triglycerides (TG). Our data shows that higher endogenous insulin secretion might play an important role in the progression of arterial stiffness in nondiabetic essential hypertensive patients.

Sun K, et al. Korean Circ J. 2027 ;57:e25. https://doi.org/10.4070/kcj.2026.0038