Emerging roles for the ubiquitin-proteasome system and autophagy in pancreatic beta-cells

Hartley T, Brumell J, Volchuk A. Emerging roles for the ubiquitin-proteasome system and autophagy in pancreatic beta-cells. Am J Physiol Endocrinol Metab 296: E1-E10, 2009. First published September 23, 2008; doi: 10.1152/ajpendo.90538.2008.-Protein degradation in eukaryotic cells is mediated primarily by the ubiquitin-proteasome system and autophagy. Turnover of protein aggregates and other cytoplasmic components, including organelles, is another function attributed to autophagy. The ubiquitin-proteasome system and autophagy are essential for normal cell function but under certain pathological conditions can be overwhelmed, which can lead to adverse effects in cells. In this review we will focus primarily on the insulin-producing pancreatic beta-cell. Pancreatic beta-cells respond to glucose levels by both producing and secreting insulin. The inability of beta-cells to secrete sufficient insulin is a major contributory factor in the development of type 2 diabetes. The aim of this review is to examine some of the crucial roles of the ubiquitin-proteasome system and autophagy in normal pancreatic beta-cell function and how these pathways may become dysfunctional under pathological conditions associated with metabolic syndromes.