The effect of vitamin D3 on subtypes of S100 in Streptozotocin (STZ)-induced diabetic rat model

The International Diabetes Federation (IDF) Diabetes Atlas (2021) reveals a global diabetes prevalence of 10.5% among the adult population (20-79 years). Diabetes Mellitus (DM), characterized by elevated blood sugar levels, is a prevalent metabolic disorder stemming from intricate genetic and environmental factors and involves increased non-enzymatic glycation, leading to toxic glucose derivatives known as advanced glycation end products (AGEs). S100 proteins, damage-associated molecular pattern proteins expressed in various organs, play diverse physiological and pathological roles. AGEs and S100 proteins interaction with receptor for advanced glycation end products (RAGE), contribute to oxidative stress and inflammation, linking them to diabetes-related cognitive impairment. Vitamin D3 (Vit-D3), a secosteroid hormone, exerts genomic influences through vitamin D receptor (VDR) and rapid effects via cell membrane receptors like membrane-associated rapid response steroid-binding protein (MARRSBP), triggering neuroprotective and anti-inflammatory responses. In this study, in the diabetic rat model induced by a single dose of streptozotocin (STZ) (intraperitoneal injection of 65 mg/kg), the changes in S100 protein subtypes, S100B, and S100A8/A9 (calprotectin) in serum and hippocampus samples were assessed using ELISA, focusing on Vit-D3's impact. Also, cognitive changes were assessed through the eight-arm radial maze test (RAM). The results indicate that the hippocampal RAGE, calprotectin, S100B, and insulin, along with the serum level of calprotectin, significantly increased in both the STZ and Vit-D3 groups compared to the control group; however, a significant increase in serum RAGE levels was detected only in the STZ group. The rotarod test results indicated a significant decrease in the time spent on the spindle by the STZ group, and the RAM test revealed reduced correct arm choices and prolonged latency in the STZ group. The administration of Vit-D3 was observed to reduce the increased serum RAGE levels and reverse these negative effects on motor performance and memory. Keywords: Diabetes Mellitus, RAGE, Streptozotocin, S100, Vitamin D3.