Abstract
Insulin, a vital hormone for glucose homeostasis is produced by pancreatic beta-cells and when secreted, stimulates the uptake and storage of glucose from the blood. In the pancreas, insulin is stored in vesicles termed insulin secretory granules (ISGs). In Type 2 diabetes (T2D), defects in insulin action results in peripheral insulin resistance and beta-cell compensation, ultimately leading to dysfunctional ISG production and secretion. ISGs are functionally dynamic and many proteins present either on the membrane or in the lumen of the ISG may modulate and affect different stages of ISG trafficking and secretion. Previously, studies have identified few ISG proteins and more recently, proteomics analyses of purified ISGs have uncovered potential novel ISG proteins. This review summarizes the proteins identified in the current ISG proteomes from rat insulinoma INS-1 and INS-1E cell lines. Here, we also discuss techniques of ISG isolation and purification, its challenges and potential future directions.
Highlights
Charles Perkins Centre, School of Medical Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Abstract: Insulin, a vital hormone for glucose homeostasis is produced by pancreatic beta-cells and when secreted, stimulates the uptake and storage of glucose from the blood
There is a continuous turnover of insulin granules in the beta-cell, which is highly specialised in its capacity for insulin secretory granules (ISGs) biogenesis, and insulin represents the most abundant protein within the beta-cell at 5–10% of total cell protein mass [1]
Through a secondary mechanism called ‘sorting by retention’, proinsulin and other proteins are retained in the immature ISG (Davidson et al, 1988), while in parallel, proteins such as clathrin are removed from the immature ISG via
Summary
The insulin secretory granule (ISG) is the storage vesicle for insulin in pancreatic beta-cells. From its point of synthesis, proinsulin enters an ISG within 4 hours [5] and is processed into insulin in a mature ISG within 40 minutes [9]. ISG been can modulate the processing and to an ISG’s propensity for translocation to the plasma membrane and its necessity for docktrafficking of ISGs, controlling granule mobility, secretion capacity, and degraing [16,18]. As insulin accounts for a large proportion of protein synthesis in pancreatic beta-cells [21], ISG homeostasis is essential to maintaining beta-cell function [22]. Pathological dysfunction related to insulin occurs at all stages, from synthesis to secretion and primarily results in diabetes. Loss of ISG in beta-cells, termed degranulation, is characteristic of Type 2 diabetes (T2D).
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