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Autophagy and Diabetes

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Dr KK Aggarwal    05 November 2017

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 946 cells occurs to compensate for hyperglycemia and insulin resistance occurs early in the disease. As the disease progresses dysfunction and loss of 946 cells occur. 1 Autophagy is now regarded as necessary to maintain the structure and function of pancreatic 946 cells. 5 Autophagy dysfunction is associated with loss of 946 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 946 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 946 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 946 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.

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