β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes

• DOI: 10.1038/srep21924
• Publication Date: 2016-02-24T10:20:38Z
• Authors: Chang-Xiang Shi; Ming-Xia Zhao; Xiao-Dong Shu; Xiao-Qing Xiong; Jue-Jin Wang; Xing-Ya Gao; Qi Chen; Yue-Hua Li; Yu-Ming Kang; Guo-Qing Zhu
• Keywords: Blood Glucose; Glucosamine; 0303 health sciences; Aminoisobutyric Acids; Blotting, Western; Administration, Oral; Apoptosis; Hep G2 Cells; AMP-Activated Protein Kinases; Diet, High-Fat; Endoplasmic Reticulum Stress; Lipid Metabolism; Immunohistochemistry; Article; Diabetes Mellitus, Experimental; 3. Good health; Mice; 03 medical and health sciences; Cholesterol; Liver; Animals; Carbohydrate Metabolism; Humans; Insulin Resistance

Abstractβ-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.