Potential mechanisms underlying the association between type II diabetes mellitus and cognitive dysfunction in rats: a link between miRNA-21 and Resveratrol’s neuroprotective action

Abstract

Cognitive impairment is considered as a typical feature of neurodegenerative diseases in diabetes mellitus (DM). However, the exact link between cognitive dysfunction and diabetes mellitus is still vague. This study aims to investigate some of the mechanisms underlying cognitive impairment that associates diabetes mellitus and insulin resistance. We investigated the role of resveratrol as well on cognitive function in experimentally induced type 2 diabetes highlighting on its influence on the expression of brain miRNA 21. Resveratrol is a naturally occurring, biologically active compound that has numerous significant impacts on the body. Type 2 diabetes mellitus was induced by high fat diet followed a single dose of streptozotocin. Diabetic rats were treated with resveratrol for four weeks. Rats were sacrificed after neurobehavioral testing. Hippocampal tissues were used to assess expression of miRNA 21, GSK and oxidative stress markers. Serum samples were obtained to determine glucose levels, lipid profile and insulin levels. Hippocampal and serum AGEs were measured as well and HOMA IR was calculated. We detected memory impairment and disturbed insulin signaling in diabetic rats. These derangements were reversed by resveratrol treatment partially due to increased expression of miRNA-21. Our study pins the role of miRNA-21 in modulating brain insulin signaling and hence alleviating cognitive dysfunction accompanying diabetes mellitus.

The protective role of resveratrol against high glucose‐induced oxidative stress and apoptosis in HepG2 cells

“…Resveratrol, a polyphenol phytoalexin, has been studied for its potential therapeutic effects in diabetes (El-Sayed et al, 2022).…”

“…Resveratrol, a polyphenol phytoalexin, has been studied for its potential therapeutic effects in diabetes (El‐Sayed et al., 2022 ). Our results demonstrated that treatment with resveratrol reversed the reduction in the mRNA expression of SOD , CAT , GPx1 , Nrf2 , and NQO1 induced by high glucose in HepG2 cells.…”

Mitochondrial dynamics-related genes Drpl and Opal contributes to early diagnosis of cognitive impairment in diabetes

“…Oxidative stress and reduced antioxidant defenses create a deleterious combination that disrupts cell function and damages cells, leading to the loss of synapses and cell death. At the same time, hyperglycemia can also activate a variety of signaling pathways, leading to increased ROS production and insulin resistance [15].…”

Dietary Epigenetic Modulators: Unravelling the Still-Controversial Benefits of miRNAs in Nutrition and Disease

“…Resveratrol exerted beneficial action on age-related alterations, as senile sarcopenia, by promoting peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α) expression and myocyte differentiation by miR-21 and miR-27b upregulation and a decrease of miR-133b, miR-30b, and miR-149 levels [ 83 ]. In addition, the resveratrol-induced miR-21 upregulation alleviated cognitive impairment due to insulin resistance and diabetes in mice [ 84 ]. The link between saturated fatty acids (SFA) and poor health outcomes and metabolic disorders [ 85 ] is already well established; additionally, it is reported that SFA effects on human health could also depend on their influence on miRNAs [ 86 ].…”