Interleukin-4 Boosts Insulin-Induced Energy Deposits by Enhancing Glucose Uptake and Lipogenesis in Hepatocytes

Ching-Ping Yang, Ming-Yuh Shiau, Yi-Ren Lai, Kuo-Ting Ho, Chiao-Wan Hsiao, Chun-Jung Chen, Yu-Li Lo, Yih-Hsin Chang
2018 Oxidative Medicine and Cellular Longevity  
Type 2 diabetes mellitus (T2DM), with dysregulated hepatic gluconeogenesis as the major cause of fasting hyperglycemia, is closely associated with chronic inflammation. We previously demonstrated interleukin-4 (IL-4) improves insulin sensitivity and glucose tolerance while reducing lipid deposits. The present study examined the in vitro effects of IL-4 on insulin signaling molecules, glucose uptake, and lipid metabolism in hepatocytes, as well as in vivo effects on hepatic adiposity, for
more » ... ting the roles of IL-4 in hepatic energy metabolism. Potential interaction between IL-4 and insulin in regulating hepatic metabolism was also investigated. Our results showed that IL-4 enhanced Akt and GSK-3α/β phosphorylations, which in turn promoted glycogen synthesis. IL-4 not only potentiated basal glucose uptake by upregulating glucose transporter 2 expression but also promoted insulin-induced glucose uptake. Additionally, IL-4 increased triglyceride contents through facilitating free fatty acid uptake and expression/activity of lipogenic enzymes. The major effects of IL-4 on the liver were to promote energy storage by boosting insulin-stimulated glucose uptake and lipid synthesis. This study provides evidence to implicate the novel roles of IL-4 in mediating hepatic glucose and lipid metabolism, interactions between immune responses and metabolic homeostasis, and the involvement of IL-4 in metabolic abnormalities.
doi:10.1155/2018/6923187 fatcat:pg3yqcunarayrdvsybti3s76q4