Sucralose Targets the Insulin Signaling Pathway in the SH-SY5Y Neuroblastoma Cell Line

• Published in: Metabolites Vol. 13; no. 7; p. 817
• Main Authors: Čović, Marina, Zjalić, Milorad, Mihajlović, Lovro, Pap, Marianna, Wagner, Jasenka, Mandić, Dario, Debeljak, Željko, Heffer, Marija
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-07-2023; MDPI
• Subjects: AKT protein; Artificial sweeteners; Care and treatment; Cell culture; Cell differentiation; Cell viability; Chronic illnesses; Dopa; Dopamine; Dopamine receptors; dopaminergic neurons; Enzymes; Fatty acids; Food; Food additives; Glucagon; Glucose; Glycogen; Glycogen synthase kinase 3; Health aspects; Insulin; insulin like growth factor 1 receptor; Insulin resistance; insulin signaling; Insulin-like growth factor I; Ions; Levodopa; Metabolism; Metabolites; Movement disorders; Neuroblastoma; Neurodegeneration; Neurodegenerative diseases; non-nutritive sweetener; Parkinson's disease; Penicillin; Phosphorylation; Physiological aspects; Proteins; Signal transduction; Sucralose; Taste buds; Croatia; United States > US; Germany; neurodegeneration; insulin like growth factor 1 receptor; insulin signaling; non-nutritive sweetener; dopaminergic neurons
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo13070817

Sucralose is widely used as a non-nutritive sweetener (NNS). However, in order to justify its use as a non-nutritive food additive, sucralose would have to be metabolically neutral. The aim of this study was to examine whether sucralose altered the insulin signaling pathway in an in vitro cell model of Parkinson's disease (PD)-the dopaminergic differentiated cell line SH-SY5Y. Cells were exposed to sucralose alone and in combination with either insulin or levodopa. Activation of the insulin signaling pathway was assessed by quantifying protein kinase B (AKT) and glycogen synthase kinase 3 (GSK3), as well as the phosphorylated forms of insulin-like growth factor 1 receptor (IGF1-R). Metabolic effects were assayed using MALDI-TOF MS analysis. In the cell viability test, 2 mM sucralose had a negative effect, and levodopa in all combinations had a positive effect. Sucralose treatment alone suppressed GSK3 and IGF1-R phosphorylation in a dose-dependent manner. This treatment also altered the metabolism of fatty acids and amino acids, especially when combined with insulin and levodopa. Suppression of the insulin signaling pathway and sucralose-induced changes in the metabolic profile could underlie a diet-acquired insulin resistance, previously associated with neurodegeneration, or may be an altered response to insulin or levodopa medical therapy.