Author(s): EFTEKHARIRANJBAR, S.1,7, FRIGERIO, F.2,7, BERTOLLO, M.1, POURRAHIM, A.3, CARDINALI, L.4, BALDARI, C.5, GUIDETTI, L.6, DONINI, L.7, MIGLIACCIO, S.7, Institution: UNIVERSITY CHIETI PESCARA, Country: ITALY, Abstract-ID: 1529

INTRODUCTION:
Type 2 diabetes mellitus is a chronic, progressive metabolic disorder marked by insulin resistance, increased inflammation, and oxidative stress (1). While high-intensity interval training (HIIT) has shown substantial benefits in modulating angiogenesis and flogosis (2), sodium nitrite (NaNO2) supplementation has emerged as a promising agent for enhancing insulin sensitivity and reducing oxidative stress (3). Thus, our study was conducted to elucidate the effects of sodium NaNO2 and HIIT on metabolic and vascular dysfunction biomarkers of subclinical chronic inflammation.
METHODS:
To this aim diabetic rats, obtained by applying the nicotinamide-streptozotocin method, were used as experimental animal model. An overall sample of 25 male rats was assigned to one of 5 groups: control animals, diabetic animals, diabetic+NaNO2 supplementation, diabetic+HIIT, and diabetic+HIIT+NaNO2 supplementation. Exercise intervention consisted of an 8-week HIIT protocol with increasing intensity and duration, adjusted every 2 weeks based on reassessed maximum running speed. NaNO2 was administered in 3 doses via tail injection (12 nmol/kg each), with a one-week interval among doses. Specific biomarkers (i.e., TNF-alpha, MuRF1, PI3K, Klotho, and Resistin were measured in rat cardiomyocytes by ELISA). One-way ANOVA and Kruskal-Wallis tests were used for between-group comparisons, followed by Dunnett’s T3 and Dunn-Bonferroni post-hoc tests.
RESULTS:
As compared to control animals, diabetic animals displayed higher MURF-1 and TNF-alpha levels (p=0.047 and p=0.002, respectively), while greater Resistin levels were apparent both in diabetic (p=0.007) and HIIT animals p=0.008). Finally, increased Klotho levels emerged in the NaNO2+HIIT and NaNO2 groups (p=0.001 and p=0.044, respectively) compared to diabetic animals whereas significantly higher PI3K levels were apparent both in control (p<0.001) and NaNO2+HIIT (p=0.017) rats.
CONCLUSION:
In conclusion our results show that while combined intervention (NaNO2+HIIT) effectively increased both Klotho and PI3K levels, isolated NaNO2 supplementation selectively ameliorated Klotho levels at the cardiomyocyte level of diabetic rats. When administered alone, HIIT was not effective in contrasting diabetes-induced alterations in inflammatory and metabolic biomarkers in an experimental diabetic animal model.

References:
(1) Lu X, et al. Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy. Signal Transduct Target Ther. 2024 Oct 2;9(1):262
(2) Magalhães FDC, et al. High-intensity interval training followed by postexercise cold-water immersion does not alter angiogenic circulating cells, but increases circulating endothelial cells. Appl Physiol Nutr Metab. 2020 Jan;45(1):101–11
(3) Hughan KS,et al. Oral Sodium Nitrite Improves Insulin Sensitivity, Blood Pressure, and Arterial Thickening in Adults with Uncontrolled Hypertension and Metabolic Syndrome. Diabetes. 2018 Jul 1;67(S_1):75