Jaakko Sarparanta, Marina García-Macia and Rajat Singh* Pages 352 - 369 ( 18 )
Introduction: Obesity and type 2 diabetes are growing health problems worldwide. The three principal diabetogenic factors are adiposity, insulin resistance in skeletal muscle, and decreased insulin production by pancreatic β cells. During recent years, macroautophagy (hereafter autophagy) — sequestration and lysosomal degradation of cellular components — has emerged as an important player in these processes, playing a protective role against development of insulin resistance and diabetes. Of particular importance is the removal of dysfunctional mitochondria via mitophagy, a form of macroautophagy selective for mitochondria. Both muscle insulin resistance and β-cell dysfunction largely depend on metabolic overload of mitochondria, which results in incomplete β-oxidation, oxidative stress, accumulation of toxic lipid intermediates, and mitochondrial damage. Mitophagy eliminates this vicious cycle of oxidative stress and mitochondrial damage, and thus counteracts pathogenic processes. Autophagy also mediates exercise-induced increases in muscle glucose uptake and protects β cells against ER stress in diabetogenic conditions. On the other hand, adipose tissue autophagy promotes adipocyte differentiation, possibly through its role in mitochondrial clearance. Being involved in many aspects, autophagy appears to be an attractive target for therapeutic interventions against obesity and diabetes.Conclusion: Here we explore the connections of autophagy with mitochondria in obesity and type 2 diabetes, and discuss its roles in diabetic complications. Understanding how autophagy protects against diabetes could help design new strategies against this growing epidemic.
Macroautophagy, mitophagy, diabetes, muscle, adipose tissue, beta cells.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, Department of Medicine (Endocrinology), and Molecular Pharmacology, Member of the Diabetes Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer Building, Room 505D, Bronx, NY 10461