Autophagy and Diabetes
Dr KK Aggarwal
Autophagy in diabetes has recently been the focus of research and accumulating evidence has suggested a pathophysiological role for autophagy in diabetes.1 The word autophagy means “self eating” as it is derived from two Greek words “auto” meaning “self”, and “phagein” meaning “to eat”.
Autophagy is a catabolic process by which cells adapt to stress and starvation. It maintains cellular homeostasis by lysosomal-mediated degradation and recycling of damaged proteins and organelles such as mitochondria. 2,3 Three types of autophagy are described: Macroautophagy, microautophagy and chaperone-mediated autophagy. The most prevalent of these is macroautophagy.4
Hyperglycemia secondary to insulin resistance is implicated in the pathogenesis of diabetes. In the natural history of type 2 diabetes, hypertrophy of the pancreatic β-cells occurs to compensate for hyperglycemia and insulin resistance occurs early in the disease. As the disease progresses, dysfunction and loss of β-cells occur. 1
Autophagy is now regarded as necessary to maintain the structure and function of pancreatic β-cells. 5 Autophagy dysfunction is associated with loss of β-cell mass and function suggesting a possible role in the development and progression of type 2 diabetes. 6 Autophagy may affect insulin sensitivity as mitochondrial dysfunction has been implicated in insulin resistance. 2 Mitochondria dysfunction results in incomplete β-oxidation, oxidative stress, accumulation of toxic lipid intermediates and mitochondrial damage. By removing the dysfunctional mitochondria, autophagy removes the cycle of oxidative stress and mitochondrial damage.7 Autophagy also has a possible role in regulation of function of insulin-target tissues, such as skeletal muscle, liver, and adipose tissue, where it protects against oxidative stress in these tissues. 3
The Nobel Prize in Physiology or Medicine 2016 was awarded to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy.
1. Demirtas L, et al. Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus. Indian J Med Res. 2016;144(4):515-24.
2. Jung HS, et al. Role of autophagy in diabetes and mitochondria. Ann N Y Acad Sci. 2010;1201:79-83.
3. Barlow AD, et al. Autophagy in diabetes: β-cell dysfunction, insulin resistance, and complications. DNA Cell Biol. 2015;34(4):252-60.
4. Islam MT, et al. Autophagic dysfunction in type 2 diabetes mellitus: pathophysiology and therapeutic implications. J Diabetes Metab. 2017;8:742
5. Quan W, et al. Role of autophagy in the control of body metabolism. Endocrinol Metab (Seoul). 2013;28(1):6-11.
6. Mazza S, et al. Autophagy and pancreatic β-cells. Vitam Horm. 2014;95:145-64.
7. Sarparanta J, et al. Autophagy and mitochondria in obesity and type 2 diabetes. Curr Diabetes Rev. 2017;13(4):352-69.