Autophagy and Diabetes

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.

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.