Abstract
β-aminoisobutyric acid (BAIBA) is a nature thymine catabolite, and contributes to exercise-induced protection from metabolic diseases. Here we show the therapeutical effects of BAIBA on hepatic endoplasmic reticulum (ER) stress and glucose/lipid metabolic disturbance in diabetes. Type 2 diabetes was induced by combined streptozotocin (STZ) and high-fat diet (HFD) in mice. Oral administration of BAIBA for 4 weeks reduced blood glucose and lipids levels, hepatic key enzymes of gluconeogenesis and lipogenesis expressions, attenuated hepatic insulin resistance and lipid accumulation, and improved insulin signaling in type 2 diabetic mice. BAIBA reduced hepatic ER stress and apoptosis in type 2 diabetic mice. Furthermore, BAIBA alleviated ER stress in human hepatocellular carcinoma (HepG2) cells with glucosamine-induced insulin resistance. Hepatic AMPK phosphorylation was reduced in STZ/HFD mice and glucosamine-treated HepG2 cells, which were restored by BAIBA treatment. The suppressive effects of BAIBA on glucosamine-induced ER stress were reversed by knockdown of AMPK with siRNA. In addition, BAIBA prevented thapsigargin- or tunicamycin-induced ER stress, and tunicamycin–induced apoptosis in HepG2 cells. These results indicate that BAIBA attenuates hepatic ER stress, apoptosis and glucose/lipid metabolic disturbance in mice with type 2 diabetes. AMPK signaling is involved to the role of BAIBA in attenuating ER stress.
Highlights
These results indicate that the BAIBA reduces blood glucose and hepatic gluconeogenesis and improves hepatic insulin resistance in type 2 diabetes, which is associated with the improvement of insulin signaling rather than the circulating insulin levels
These results indicate that BAIBA attenuates glucosamine-induced hepatic ER stress in vivo
These results indicate that BAIBA prevented thapsigargin- tunicamycin- or high glucose-induced ER stress in vivo
Summary
ER stress plays a crucial role in the insulin resistance and could be a potential therapeutic target for diabetes[10]. BAIBA reduces body fat percentage through increased fatty acid oxidation (FAO) and decreased de novo lipogenesis in liver in mice[14]. BAIBA enhances the browning of white adipose tissue and FAO in the liver via peroxisome proliferator-activated receptor α (PPARα ), and may contribute to exercise-induced protection from metabolic diseases[13]. It has been found that BAIBA attenuates insulin resistance, inhibits inflammation and induces FAO in skeletal muscle via AMPK-PPARδ pathway[15]. The therapeutic effects of BAIBA on hepatic ER stress, apoptosis and glucose/lipid metabolic disturbance in type 2 diabetes were investigated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
