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β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes.
Sci Rep. 2016 Feb 24; 6:21924.SR

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.

Authors+Show Affiliations

Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.Department of Physiology and Pathophysiology, Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China. Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26907958

Citation

Shi, Chang-Xiang, et al. "Β-aminoisobutyric Acid Attenuates Hepatic Endoplasmic Reticulum Stress and Glucose/lipid Metabolic Disturbance in Mice With Type 2 Diabetes." Scientific Reports, vol. 6, 2016, p. 21924.
Shi CX, Zhao MX, Shu XD, et al. Β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes. Sci Rep. 2016;6:21924.
Shi, C. X., Zhao, M. X., Shu, X. D., Xiong, X. Q., Wang, J. J., Gao, X. Y., Chen, Q., Li, Y. H., Kang, Y. M., & Zhu, G. Q. (2016). Β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes. Scientific Reports, 6, 21924. https://doi.org/10.1038/srep21924
Shi CX, et al. Β-aminoisobutyric Acid Attenuates Hepatic Endoplasmic Reticulum Stress and Glucose/lipid Metabolic Disturbance in Mice With Type 2 Diabetes. Sci Rep. 2016 Feb 24;6:21924. PubMed PMID: 26907958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes. AU - Shi,Chang-Xiang, AU - Zhao,Ming-Xia, AU - Shu,Xiao-Dong, AU - Xiong,Xiao-Qing, AU - Wang,Jue-Jin, AU - Gao,Xing-Ya, AU - Chen,Qi, AU - Li,Yue-Hua, AU - Kang,Yu-Ming, AU - Zhu,Guo-Qing, Y1 - 2016/02/24/ PY - 2015/11/10/received PY - 2016/02/02/accepted PY - 2016/2/25/entrez PY - 2016/2/26/pubmed PY - 2016/12/21/medline SP - 21924 EP - 21924 JF - Scientific reports JO - Sci Rep VL - 6 N2 - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/26907958/β_aminoisobutyric_acid_attenuates_hepatic_endoplasmic_reticulum_stress_and_glucose/lipid_metabolic_disturbance_in_mice_with_type_2_diabetes_ L2 - http://dx.doi.org/10.1038/srep21924 DB - PRIME DP - Unbound Medicine ER -