title: The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment.
abstract: The type 2 diabetes pandemic in recent decades is a huge global health threat. This pandemic is primarily attributed to the surplus of nutrients and the increased prevalence of obesity worldwide. In contrast, calorie restriction and weight reduction can drastically prevent type 2 diabetes, indicating a central role of nutrient excess in the development of diabetes. Recently, the molecular links between excessive nutrients, organelle stress, and development of metabolic disease have been extensively studied. Specifically, excessive nutrients trigger endoplasmic reticulum stress and increase the production of mitochondrial reactive oxygen species, leading to activation of stress signaling pathway, inflammatory response, lipogenesis, and pancreatic beta-cell death. Autophagy is required for clearance of hepatic lipid clearance, alleviation of pancreatic beta-cell stress, and white adipocyte differentiation. ROS scavengers, chemical chaperones, and autophagy activators have demonstrated promising effects for the treatment of insulin resistance and diabetes in preclinical models. Further results from clinical trials are eagerly awaited.
authors.affiliation: Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei 100, Taiwan ; Department of Internal Medicine and Center for Obesity, Lifestyle and Metabolic Surgery, National Taiwan University Hospital, Taipei 100, Taiwan ; Institute of Biomedical Science, Academia Sinica, Taipei 100, Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine and Center for Obesity, Lifestyle and Metabolic Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Siow-Wey
authors.initials: SW
authors.lastname: Hee
authors.affiliation: Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Meng-Lun
authors.initials: ML
authors.lastname: Hsieh
authors.affiliation: Graduate Institute of Pathology, National Taiwan University, Taipei 100, Taiwan ; Department of Pathology, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.affiliation: Department of Internal Medicine and Center for Obesity, Lifestyle and Metabolic Surgery, National Taiwan University Hospital, Taipei 100, Taiwan ; College of Medicine, National Taiwan University, Taipei 100, Taiwan ; Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D000818:Animals; D001343:Autophagy; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D006801:Humans; D008928:Mitochondria / Q000473:pathology; D009765:Obesity / Q000473:pathology*; D015388:Organelles / Q000473:pathology*; D013312:Stress, Physiological