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

• Published in: Metabolites Vol. 13; no. 2; p. 269
• Main Authors: Subash-Babu, Pandurangan, Abdulaziz AlSedairy, Sahar, Abdulaziz Binobead, Manal, Alshatwi, Ali A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.02.2023; MDPI
• Subjects: Apoptosis; Bioflavonoids; Biological activity; Cell lines; Cells; CYP1A protein; Cytochrome P450; Cytokines; Dextrose; Diabetes; Diabetes mellitus (non-insulin dependent); Fatty acids; Flavones; Flavonoids; Gene expression; Glucose; glucose homeostasis; Glycerol; Health aspects; Homeostasis; Hyperglycemia; Inflammation; Insulin; Insulin resistance; Insulin secretion; Intracellular signalling; L6 myotubes; Lactic acid; luteolin-7-O-rutinoside; Metabolism; Mitochondria; Molecular biology; Molecular modelling; Morphology; Musculoskeletal system; Myotubes; NF-κB protein; Oxidative stress; Pharmacology, Experimental; Physiological aspects; Prevention; RIN-5F cells; Rosiglitazone; Rutin; Secretion; Thermogenesis; Toxicity; Tumor necrosis factor-α; Type 2 diabetes; Saudi Arabia; St Louis Missouri; United States > US; Germany; glucose homeostasis; luteolin-7-O-rutinoside; L6 myotubes; mitochondria; RIN-5F cells
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo13020269

Luteolin-7 -rutinoside (lut-7 -rutin), a flavonoid commonly present in L. and 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 rutin on high-glucose-induced toxicity to RIN-5F cells in vitro. We found that lut-7 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 rutin improves insulin sensitization and glucose uptake significantly ( ≤ 0.01) in L6 myotubes cultured in a high-glucose medium. Lut-7 rutin has shown a significant ( ≤ 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 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 rutin protects RIN-5F cells from high-glucose-induced toxicity, stimulates insulin secretion, and promotes glucose absorption and homeostasis via molecular mechanisms.