Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes

Abstract

Luteolin-7-O-rutinoside (lut-7-O-rutin), a flavonoid commonly present in Mentha longifolia L. and Olea europaea L. leaves has been used as a flavoring agent with some biological activity. The present study is the first attempt to analyze the protective effect of lut-7-O-rutin on high-glucose-induced toxicity to RIN-5F cells in vitro. We found that lut-7-O-rutin improved insulin secretion in both normal and high-glucose conditions in a dose-dependent manner, without toxicity observed. In addition, 20 µmol of lut-7-O-rutin improves insulin sensitization and glucose uptake significantly (p ≤ 0.01) in L6 myotubes cultured in a high-glucose medium. Lut-7-O-rutin has shown a significant (p ≤ 0.05) effect on glucose uptake in L6 myotubes compared to the reference drug, rosiglitazone (20 µmol). Gene expression analysis confirmed significantly lowered CYP1A, TNF-α, and NF-κb expressions in RIN-5F cells, and increased mitochondrial thermogenesis-related LPL, Ucp-1 and PPARγC1A mRNA expressions in L6 myotubes after 24 h of lut-7-O-rutin treatment. The levels of signaling proteins associated with intracellular glucose uptakes, such as cAMP, ChREBP-1, and AMPK, were significantly increased in L6 myotubes. In addition, the levels of the conversion rate of glucose to lactate and fatty acids were raised in insulin-stimulated conditions; the rate of glycerol conversion was found to be higher at the basal level in L6 myotubes. In conclusion, lut-7-O-rutin protects RIN-5F cells from high-glucose-induced toxicity, stimulates insulin secretion, and promotes glucose absorption and homeostasis via molecular mechanisms.