RESUMEN
Diabetic nephropathy (DN) is a serious public health problem worldwide, and ferroptosis is deeply involved in the pathogenesis of DN. Prediabetes is a critical period in the prevention and control of diabetes and its complications, in which kidney injury occurs. This study aimed to explore whether ferroptosis would induce kidney injury in prediabetic mice, and whether vitamin D (VD) supplementation is capable of preventing kidney injury by inhibiting ferroptosis, while discussing the potential mechanisms. High-fat diet (HFD) fed KKAy mice and high glucose (HG) treated HK-2 cells were used as experimental subjects in the current study. Our results revealed that serious injury and ferroptosis take place in the kidney tissue of prediabetic mice; furthermore, VD intervention significantly improved the kidney structure and function in prediabetic mice and inhibited ferroptosis, showing ameliorated iron deposition, enhanced antioxidant capability, reduced reactive oxygen species (ROS) and lipid peroxidation accumulation. Meanwhile, VD up-regulated Klotho, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, and down-regulated p53, transferrin receptor 1 (TFR1) and Acyl-Coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Moreover, we demonstrated that HG-induced ferroptosis is antagonized by treatment of VD and knockdown of Klotho attenuates the protective effect of VD on ferroptosis in vitro. In conclusion, ferroptosis occurs in the kidney of prediabetic mice and VD owns a protective effect on prediabetic kidney injury, possibly by via the Klotho/p53 pathway, thus inhibiting hyperglycemia-induced ferroptosis.
RESUMEN
PURPOSE: The aim of this study was to evaluate the effects of vitamin D and/or calcium supplementation on sleep quality in individuals with prediabetes. METHODS: A 24-week randomized controlled trial (RCT) was conducted in a 212 Chinese population with prediabetes. Participants were randomly assigned to four groups: vitamin D + calcium group (1600 IU/day + 500 mg/day, n = 53), vitamin D group (1600 IU/day, n = 54), calcium group (500 mg/day, n = 51), and control group (placebo, n = 54). The Pittsburgh Sleep Quality Index (PSQI) was used as the primary outcome to assess sleep quality. Questionnaires and fasting blood samples were collected at baseline and post-intervention for demographic assessment and correlation index analysis. RESULTS: After a 24-week intervention, a significant difference was observed in serum 25(OH)D concentration among the four groups (P < 0.05), and the total PSQI score in vitamin D + calcium group was lower compared to the preintervention levels. Subgroup analyses revealed improved sleep quality with calcium supplementation (P < 0.05) for specific groups, including women, individuals with a low baseline 25(OH)D level (< 30 ng/mL), and individuals in menopause. Moreover, correlation analysis revealed a negative correlation between the extent of change in sleep efficiency scores before and after the calcium intervention and the degree of change in insulin efficiency scores (r = - 0.264, P = 0.007), as well as the magnitude of change in islet beta cell function (r = - 0.304, P = 0.002). CONCLUSIONS: The combined intervention of vitamin D and calcium, as well as calcium interventions alone, exhibits substantial potential for improving sleep quality in individuals with prediabetes. CLINICAL TRIAL REGISTRATION: The trial was registered in August 2019 as ChiCTR190002487.
Asunto(s)
Suplementos Dietéticos , Estado Prediabético , Calidad del Sueño , Vitamina D , Humanos , Estado Prediabético/complicaciones , Estado Prediabético/dietoterapia , Estado Prediabético/sangre , Femenino , Vitamina D/sangre , Vitamina D/administración & dosificación , Masculino , Persona de Mediana Edad , Calcio de la Dieta/administración & dosificación , Adulto , Anciano , China , Método Doble Ciego , Vitaminas/administración & dosificación , Vitaminas/farmacologíaRESUMEN
Prediabetes is a crucial stage for prevention and treatment of diabetes, and vitamin D (VD) has been found to be linked to the development of prediabetes and diabetes. Thus, we aimed to identify the effect of VD supplementation on glucose metabolism in prediabetic participants and mice. A 1:1 paired design of randomized, placebo-controlled trial with 1600 IU/day VD3 or placebo was administered to individuals with prediabetes, two-way repeated-measures ANCOVA was used to analyze glycolipid and inflammatory factors. A high-fat diet induced prediabetic KKay mice were utilized to evaluate the effects of VD3 with 16 weeks supplementation. Generalized estimation equation, one way ANOVA were used to analyze continuous monitoring indexes and terminal indexes, respectively. Exercise capacity, skeletal muscle pathological features and relevant proteins were examined. The clinical results showed that VD3 could improve insulin secretion and decrease inflammation. Results of KKay mice exhibited that VD3 not only ameliorate glycolipid metabolism and inflammatory indicators, but also regulated pathological changes of skeletal muscle and exercise capacity. Mechanistically, our results demonstrated that VD3 could inhibit the TLR4/NFκB and activate PI3K/AKT signaling pathway. Collectively, the study indicated that VD3 exerts its beneficial effects by inhibiting TLR4/NFκB to decrease inflammatory response, and activating PI3K/AKT signaling pathway to regulate glucose homeostasis.