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 Mitochondrial 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.

References

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.