PMID- 37512524
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230801
IS  - 2218-1989 (Print)
IS  - 2218-1989 (Electronic)
IS  - 2218-1989 (Linking)
VI  - 13
IP  - 7
DP  - 2023 Jul 4
TI  - Sucralose Targets the Insulin Signaling Pathway in the SH-SY5Y Neuroblastoma Cell 
      Line.
LID - 10.3390/metabo13070817 [doi]
LID - 817
AB  - 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.
FAU - Covic, Marina
AU  - Covic M
AUID- ORCID: 0000-0003-1206-782X
AD  - Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj 
      Strossmayer University of Osijek, 31000 Osijek, Croatia.
AD  - Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and 
      Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
FAU - Zjalic, Milorad
AU  - Zjalic M
AUID- ORCID: 0000-0003-4076-2942
AD  - Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj 
      Strossmayer University of Osijek, 31000 Osijek, Croatia.
AD  - Department of Molecular Medicine and Biotechnology, Faculty of Medicine, 
      University of Rijeka, 51000 Rijeka, Croatia.
FAU - Mihajlovic, Lovro
AU  - Mihajlovic L
AD  - Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj 
      Strossmayer University of Osijek, 31000 Osijek, Croatia.
FAU - Pap, Marianna
AU  - Pap M
AUID- ORCID: 0009-0003-1220-8239
AD  - Department of Medical Biology and Central Electron Microscopic Laboratory, 
      University of Pecs Medical School, 7624 Pecs, Hungary.
FAU - Wagner, Jasenka
AU  - Wagner J
AUID- ORCID: 0000-0002-1126-7523
AD  - Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj 
      Strossmayer University of Osijek, 31000 Osijek, Croatia.
FAU - Mandic, Dario
AU  - Mandic D
AUID- ORCID: 0000-0002-3792-4384
AD  - Clinical Institute of Laboratory Diagnostics, Osijek University Hospital, 31000 
      Osijek, Croatia.
AD  - Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of 
      Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
FAU - Debeljak, Zeljko
AU  - Debeljak Z
AD  - Clinical Institute of Laboratory Diagnostics, Osijek University Hospital, 31000 
      Osijek, Croatia.
AD  - Department of Pharmacology, Faculty of Medicine, Josip Juraj Strossmayer 
      University of Osijek, 31000 Osijek, Croatia.
FAU - Heffer, Marija
AU  - Heffer M
AUID- ORCID: 0000-0001-6770-7359
AD  - Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj 
      Strossmayer University of Osijek, 31000 Osijek, Croatia.
LA  - eng
GR  - IP-09-2014/Croatian Science Foundation/
GR  - KK.01.1.1.02.0015/European Regional Development and Croatian Ministry of Science 
      fund/
PT  - Journal Article
DEP - 20230704
PL  - Switzerland
TA  - Metabolites
JT  - Metabolites
JID - 101578790
PMC - PMC10385368
OTO - NOTNLM
OT  - dopaminergic neurons
OT  - insulin like growth factor 1 receptor
OT  - insulin signaling
OT  - neurodegeneration
OT  - non-nutritive sweetener
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/29 11:52
MHDA- 2023/07/29 11:53
PMCR- 2023/07/04
CRDT- 2023/07/29 01:30
PHST- 2023/06/12 00:00 [received]
PHST- 2023/06/27 00:00 [revised]
PHST- 2023/06/29 00:00 [accepted]
PHST- 2023/07/29 11:53 [medline]
PHST- 2023/07/29 11:52 [pubmed]
PHST- 2023/07/29 01:30 [entrez]
PHST- 2023/07/04 00:00 [pmc-release]
AID - metabo13070817 [pii]
AID - metabolites-13-00817 [pii]
AID - 10.3390/metabo13070817 [doi]
PST - epublish
SO  - Metabolites. 2023 Jul 4;13(7):817. doi: 10.3390/metabo13070817.