The islets of Langerhans are micro-organs localized within the pancreas that account for nearly 2% of the total pancreatic mass. These islets consist of at least five types of endocrine cells, including glucagon-producing α cells, insulin-producing β cells, somatostatin-producing δ cells, pancreatic polypeptide-producing pancreatic polypeptide cells and ghrelin-producing ε cells [1
]. Among these cells, the insulin-producing β cells are the predominant cell type, contributing to approximately 70% of all islet cells [2
], and the secreted insulin serves as the primary regulator of blood glucose homeostasis. Elevated blood glucose levels promote insulin synthesis, as well as its secretion from β cell secretory granules. In turn, the secreted insulin promotes glucose uptake in peripheral insulin-sensitive tissues, such as liver, muscle and adipose tissues, thus regulating blood glucose back to normal levels.
Impaired insulin secretion from pancreatic β cells is one of the major factors associated with both Type 1 and Type 2 diabetes mellitus. Type 1 diabetes mellitus (T1DM) is characterized by a loss of insulin-producing β cells due to an autoimmune attack that often leads to complete insulin deficiency. On the other hand, Type 2 diabetes mellitus (T2DM) is characterized by a relative reduction in insulin secretion due to β-cell loss or β-cell dysfunction combined with insulin resistance in the peripheral tissues. A significant loss of β cell mass is characteristic in T1DM and late stages of T2DM [3
]. There are several lines of evidence pointing to a variety of mechanisms for β cell loss, including autoimmune attack [6
], lipotoxicity [7
], glucose toxicity [9
], amyloid deposition [10
], glutamate toxicity [11
] and altered insulin receptor signaling [12
]. Importantly, a more detailed understanding of the molecular pathways associated with β-cell function and the development of diabetes will benefit the development of novel therapeutic strategies for diabetes.
Biological studies geared towards unraveling the molecular mechanisms of islet functions, such as regulation of insulin secretion and β-cell loss, have accelerated as a result of increasingly available genome sequences and continuously improving genomic and proteomic technologies. Benefiting from the recent advances in mass spectrometry (MS) and bioinformatics, proteomics is now capable of identifying and quantifying thousands of proteins from isolated pancreatic islets [13
], islet-derived primary cell cultures [18
], islet-related cell lines [19
] and subcellular organelles from islet-related cell lines [22
]. Herein, we review some of the studies involving isolated pancreatic islets, primarily focusing on advances afforded by quantitative proteomic applications in islet biology over the past 5 years. Earlier studies on islet proteomics were covered by a prior review [25
]. Before delving into these studies, we will provide a brief overview of the quantitative proteomic technologies.