Kinetic aspects of compartmental storage and secretion of insulin and zinc

Gold, Gerald; Grodsky, Gerold M.

doi:10.1007/bf01971458

Cited by 64 publications

(54 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Zinc is required for insulin synthesis and storage (3), and thus large amounts of zinc are released with insulin after glucose stimulation (2). Additionally, considering the anatomical structure of the islets of Langerhans, it is likely that the ␤-cells also modulate the function of neighboring cells via paracrine/autocrine interactions.…”

Section: Discussionmentioning

confidence: 99%

Identification and Cloning of a β-Cell–Specific Zinc Transporter, ZnT-8, Localized Into Insulin Secretory Granules

Chimienti¹,

Devergnas²,

Favier³

et al. 2004

Diabetes

440

340

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Identification and Cloning of a β-Cell–Specific Zinc Transporter, ZnT-8, Localized Into Insulin Secretory Granules

Chimienti¹,

Devergnas²,

Favier³

et al. 2004

Diabetes

440

340

View full text Add to dashboard Cite

“…The precise subcellular localization and distribution of Zn 2ϩ in islets is also under debate. Histological data in fixed cells have shown mainly granular localization of Zn 2ϩ (27,28), whereas experiments with fractionation of islets have demonstrated that only 20 -30% of the total islet Zn 2ϩ was associated with the granular fraction (26,29). Given the significance of Zn 2ϩ for proinsulin biosynthesis and exocytosis, understanding the mechanisms of its uptake into islet cells is important.…”

Section: ؉mentioning

confidence: 99%

The Zn2+-transporting Pathways in Pancreatic β-Cells

Gyulkhandanyan

Lee

Bikopoulos

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…This result suggests that fluorescent cargo proteins do not report the fate of native cargo during exocytosis and leaves open the question of what happens to the native cargo of an insulin vesicle during exocytosis. We address this question here, taking advantage of fluorescent dyes that, as we demonstrate, can stain insulin vesicle dense cores and track dispersion of native insulin vesicle cargo.According to the simplest model of insulin vesicle exocytosis, a vesicle fuses with the plasma membrane and then releases all of its cargo rapidly and completely (14,15). If all insulin vesicles behaved according to the simplest model of exocytosis, then insulin vesicles should release approximately equal quantities of insulin and Cpeptide, an insulin-processing fragment also stored in insulin vesicles.…”

mentioning

confidence: 99%

“…According to the simplest model of insulin vesicle exocytosis, a vesicle fuses with the plasma membrane and then releases all of its cargo rapidly and completely (14,15). If all insulin vesicles behaved according to the simplest model of exocytosis, then insulin vesicles should release approximately equal quantities of insulin and Cpeptide, an insulin-processing fragment also stored in insulin vesicles.…”

mentioning

confidence: 99%

Pancreatic β-Cells Secrete Insulin in Fast- and Slow-Release Forms

et al. 2006

View full text Add to dashboard Cite

Insulin vesicles contain a chemically rich mixture of cargo that includes ions, small molecules, and proteins. At present, it is unclear if all components of this cargo escape from the vesicle at the same rate or to the same extent during exocytosis. Here, we demonstrate through real-time imaging that individual rat and human pancreatic ␤-cells secrete insulin in heterogeneous forms that disperse either rapidly or slowly. In healthy pancreatic ␤-cells maintained in culture, most vesicles discharge insulin in its fastrelease form, a form that leaves individual vesicles in a few hundred milliseconds. The fast-release form of insulin leaves vesicles as rapidly as C-peptide leaves vesicles. Healthy ␤-cells also secrete a slow-release form of insulin that leaves vesicles more slowly than C-peptide, over times ranging from seconds to minutes. Individual ␤-cells make vesicles with both forms of insulin, though not all vesicles contain both forms of insulin. In addition, we confirm that insulin vesicles store their cargo in two functionally distinct compartments: an acidic solution, or halo, and a condensed core. Thus, our results suggest two important features of the condensed core: 1) It exists in different states among the vesicles undergoing exocytosis and 2) its dissolution determines the availability of insulin during exocytosis. Diabetes 55:600 -607, 2006 I nsufficient insulin secretion in the face of insulin resistance leads to the disease type 2 diabetes (1). The mechanism responsible for insufficient insulin secretion remains unclear. Before it is possible to understand why insulin secretion fails to compensate for insulin resistance during the progression of type 2 diabetes (2), it is essential to understand insulin secretion at all levels of biological complexity, ranging from the whole pancreas within a living animal to the pancreatic ␤-cell and its fundamental unit of secretion, the insulin secretory vesicle.Insulin vesicles contain a chemically complex mixture of ions, small molecules, and proteins (3,4). Among the ions, there are large amounts of two divalent cations: zinc and calcium (5). Both of these ions are believed to play important roles in the regulated secretion of insulin (6). Among the vesicle proteins, insulin-related peptides comprise ϳ75% of the mass (7). The remaining 25% of the protein mass includes more than a hundred different membrane and cargo proteins. Although our understanding of regulated secretion of insulin has progressed greatly in recent years, the mechanisms that control the trafficking, processing, and secretion of insulin vesicle cargo are still matters of debate and extensive research (8).Previously, we (9) and others (10 -13) have studied secretion from single insulin vesicles by imaging fluorescently tagged proteins consisting of a vesicle cargo protein linked to a fluorescent protein. The fluorescently tagged vesicle cargo proteins, hereafter referred to as fluorescent cargo proteins, have provided a valuable and powerful tool for studies of single vesicle exocytosis. H...

show abstract

Kinetic aspects of compartmental storage and secretion of insulin and zinc

Cited by 64 publications

References 109 publications

Identification and Cloning of a β-Cell–Specific Zinc Transporter, ZnT-8, Localized Into Insulin Secretory Granules

Identification and Cloning of a β-Cell–Specific Zinc Transporter, ZnT-8, Localized Into Insulin Secretory Granules

The Zn2+-transporting Pathways in Pancreatic β-Cells

Pancreatic β-Cells Secrete Insulin in Fast- and Slow-Release Forms

Contact Info

Product

Resources

About