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Analytical Cellular Pathology
Volume 2015 (2015), Article ID 972891, 14 pages
http://dx.doi.org/10.1155/2015/972891
Review Article

The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment

1Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei 100, Taiwan
2Department of Internal Medicine and Center for Obesity, Lifestyle and Metabolic Surgery, National Taiwan University Hospital, Taipei 100, Taiwan
3Institute of Biomedical Science, Academia Sinica, Taipei 100, Taiwan
4Graduate Institute of Pathology, National Taiwan University, Taipei 100, Taiwan
5Department of Pathology, National Taiwan University Hospital, Taipei 100, Taiwan
6College of Medicine, National Taiwan University, Taipei 100, Taiwan
7Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan

Received 15 August 2015; Accepted 8 October 2015

Academic Editor: Poornima Mahavadi

Copyright © 2015 Yi-Cheng Chang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.