Long-Term Consumption of Sucralose Induces Hepatic Insulin Resistance through an Extracellular Signal-Regulated Kinase 1/2-Dependent Pathway

Meng Jie Tsai, Chung Hao Li, Hung Tsung Wu, Hsin Yu Kuo, Chung Teng Wang, Hsiu Ling Pai, Chih Jen Chang, Horng Yih Ou

研究成果: Article同行評審

3 引文 斯高帕斯(Scopus)

摘要

Sugar substitutes have been recommended to be used for weight and glycemic control. However, numerous studies indicate that consumption of artificial sweeteners exerts adverse effects on glycemic homeostasis. Although sucralose is among the most extensively utilized sweeteners in food products, the effects and detailed mechanisms of sucralose on insulin sensitivity remain ambiguous. In this study, we found that bolus administration of sucralose by oral gavage enhanced insulin secretion to decrease plasma glucose levels in mice. In addition, mice were randomly allocated into three groups, chow diet, high-fat diet (HFD), and HFD supplemented with sucralose (HFSUC), to investigate the effects of long-term consumption of sucralose on glucose homeostasis. In contrast to the effects of sucralose with bolus administration, the supplement of sucralose augmented HFD-induced insulin resistance and glucose intolerance, determined by glucose and insulin tolerance tests. In addition, we found that administration of extracellular signal-regulated kinase (ERK)-1/2 inhibitor reversed the effects of sucralose on glucose intolerance and insulin resistance in mice. Moreover, blockade of taste receptor type 1 member 3 (T1R3) by lactisole or pretreatment of endoplasmic reticulum stress inhibitors diminished sucralose-induced insulin resistance in HepG2 cells. Taken together, sucralose augmented HFD-induced insulin resistance in mice, and interrupted insulin signals through a T1R3-ERK1/2-dependent pathway in the liver.

原文English
文章編號2814
期刊Nutrients
15
發行號12
DOIs
出版狀態Published - 2023 6月

All Science Journal Classification (ASJC) codes

  • 食品科學
  • 營養與營養學

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