Vitamin D3 mitigates myopathy and metabolic dysfunction in rats with metabolic syndrome: the potential role of dipeptidyl peptidase-4.

Autor: Shoier NO; Pharmacology and Toxicology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt., Ghareib SA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt., Kothayer H; Medicinal Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt., Alsemeh AE; Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt., El-Sayed SS; Pharmacology and Toxicology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt. ssothman@pharmacy.zu.edu.eg.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Oct 02. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1007/s00210-024-03439-3
Abstrakt: Metabolic syndrome is associated with vitamin D3 deficiency. This work aims to examine the efficacy of vitamin D3 in inhibiting MetS-induced myopathy and to determine whether the beneficial effects of vitamin D3 are mediated by the inhibition of dipeptidyl peptidase-4 (DPP-4). An in silico study investigated the potential effectiveness of vitamin D3 on the inhibition of the DPP-4 enzyme. An in vitro assay of the DPP-4 inhibitory effect of vitamin D3 was performed. In vivo and over 12 weeks, both diet (with 3% salt) and drinking water (with 10% fructose) were utilized to induce MetS. In the seventh week, rats received either vitamin D3, vildagliptin, a combination of both, or vehicles. Serum lipids, adipokines, glycemic indices, and glucagon-like peptide-1 (GLP-1), muscular glucose transporter type-4 (GLUT-4) content, DPP-4, adenosine monophosphate kinase (AMPK) activities, and Sudan Black B-stained lipids were assessed. Muscular reactive oxygen species (ROS), caspase-3, and desmin immunostaining were used to determine myopathy. MetS-induced metabolic dysfunction was ameliorated by vitamin D3, which also reduced intramuscular glycogen and lipid accumulation. This is demonstrated by the attenuation of MetS-induced myopathy by vitamin D3, decreased oxidative stress, increased desmin immuno-expression, and caspase-3 activity. Our in silico data demonstrated that vitamin D3 is capable of inhibiting DPP-4, which is further supported by biochemical findings. Vitamin D3 increased serum GLP-1, muscular AMPK activity, and GLUT-4 content, whereas the levels of muscular ROS were decreased in MetS. Vildagliptin and its combination with vitamin D3 yielded comparable results. It is suggested that the DPP-4 inhibitory potential of vitamin D3 is responsible for the amelioration of MetS-induced metabolic changes and myopathy.
(© 2024. The Author(s).)
Databáze: MEDLINE
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