Regulation of Insulin Release at Pre-exocytotic Stages of the Secretory Process

Niki, I.; Senda, T.
September 2002
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic ;Sep2002, Vol. 2 Issue 3, p219
Academic Journal
Secretory output of insulin from the pancreatic beta cell is regulated in a sophisticated manner by nutrients, hormones and neurotransmitters,having impact on the different stages of the sequential events leading to release into the blood to maintain glucose homeostasis. Although the final step of the secretory process, exocytosis, has relatively been well investigated, the significance of pre-exocytotic processes such as granule movement and interaction with the plasma membrane has received less attention. Recently, we and a few other groups directly analysed the nature of intracellular traffic of insulin granules as well as their distribution. Glucose, the most important insulin secretagogue, was found to activate pre-exocytotic events as well as actual exocytosis, whereas some hormones, neurotransmitters and pharmacological substances were found to act solely on the earlier stages to potentiate insulin release. Mechanisms regulating granule traffic, access, docking and priming were found to be distinct from those for granule exocytosis, which dominantly depends on Ca2+ influx from the extracellular space. Recent studies have suggested that overloading of Ca2+may cause apoptotic death of the beta cell. We, therefore, suggest here that elucidation of the pre-exocytotic steps may allow an increase in insulin output with a minimal rise in the intracellular Ca2+ concentration, which would be helpful to prevent beta-cell loss and maintain beta cell functions under diabetic conditions.


Related Articles

  • Munc18b regulates Insulin Secretion by Docking of SSecretory Granule in Pancreatic Islet β-cells. Lam, Patrick P.; Yu He; Xie Li; Wan, Wilson C.; Kauppi, Maria; Olkkonen, Vesa M.; Gaisano, Herbert Y. // Diabetes;Jun2007 Supplement 1, Vol. 56, pA3 

    Secretory granules (SGs) are docked at the plasma membrane (PM), then becomes primed before undergoing exocytic fusion. See 1/Munc18 (SM) proteins are priming factors, in part by activating cognate Syntaxins (Syn-1 through Syn-4) on their interactions with SNARE exocytic partners that mediate...

  • Polypyrimidine tract-binding protein promotes insulin secretory granule biogenesis. Knoch, Klaus-Peter; Bergert, Hendrik; Borgonovo, Barbara; Saeger, Hans-Detlev; Altkrüger, Anke; Verkade, Paul; Solimena, Michele // Nature Cell Biology;Mar2004, Vol. 6 Issue 3, p8 

    Pancreatic ß-cells store insulin in secretory granules that undergo exocytosis upon glucose stimulation. Sustained stimulation depletes ß-cells of their granule pool, which must be quickly restored. However, the factors promoting rapid granule biogenesis are unknown. Here we show that...

  • Liraglutide, a GLP-1 Analog, Stimulates both Exocytosis and Mobilization of Insulin Granules. Ma, Li; Labno, Christine; Kuznetsov, Andrey; Bindokas, Vytautas P.; Philipson, Louis H. // Diabetes;Jun2007 Supplement 1, Vol. 56, pA436 

    GLP-1 increases cAMP and stimulates insulin granule exocytosis but the effects on insulin granule dynamics are incompletely understood. We used total internal reflection fluorescence (TIRF) microscopy to image the exocytosis and transport of GFP-insulin granules near the plasma membrane in...

  • Single Point Mutations Result in the Miss-Sorting of Glut4 to a Novel Membrane Compartment Associated with Stress Granule Proteins. Song, XiaoMei; Lichti, Cheryl F.; Townsend, R. Reid; Mueckler, Mike // PLoS ONE;Jul2013, Vol. 8 Issue 7, p1 

    Insulin increases cellular glucose uptake and metabolism in the postprandial state by acutely stimulating the translocation of the Glut4 glucose transporter from intracellular membrane compartments to the cell surface in muscle and fat cells. The intracellular targeting of Glut4 is dictated by...

  • Real-Time Measurement of F-Actin Remodelling during Exocytosis Using Lifeact-EGFP Transgenic Animals. Yujin Jang; Soekmadji, Carolina; Mitchell, Justin M.; Thomas, Walter G.; Thorn, Peter // PLoS ONE;Jul2012, Vol. 7 Issue 7, p1 

    F-actin remodelling is essential for a wide variety of cell processes. It is important in exocytosis, where F-actin coats fusing exocytic granules. The purpose of these F-actin coats is unknown. They may be important in stabilizing the fused granules, they may play a contractile role and promote...

  • Synergy of glucose and growth hormone signalling in islet cells through ICA512 and STAT5. Mziaut, Hassan; Trajkovski, Mirko; Kersting, Stephan; Ehninger, Armin; Altkrüger, Anke; Lemaitre, Régis P.; Schmidt, Darja; Saeger, Hans-Detlev; Lee, Myung-Shik; Drechsel, David N.; Müller, Stefan; Solimena, Michele // Nature Cell Biology;May2006, Vol. 8 Issue 5, p435 

    Nutrients and growth hormones promote insulin production and the proliferation of pancreatic β-cells. An imbalance between ever-increasing metabolic demands and insulin output causes diabetes. Recent evidence indicates that β-cells enhance insulin gene expression depending on their...

  • Zinc and insulin in pancreatic beta-cells. Li, Yang // Endocrine (1355008X);Mar2014, Vol. 45 Issue 2, p178 

    Zinc (Zn) is an essential element crucial for growth and development, and also plays a role in cell signaling for cellular processes like cell division and apoptosis. In the mammalian pancreas, Zn is essential for the correct processing, storage, secretion, and action of insulin in beta...

  • Glucokinase Is an Integral Component of the Insulin Granules in Glucose-Responsive Insulin Secretory Cells and Does Not Translocate During Glucose Stimulation. Arden, Catherine; Harbottle, Andrew; Baltrusch, Simone; Tiedge, Markus; Agius, Loranne // Diabetes;Sep2004, Vol. 53 Issue 9, p2346 

    The association of glucokinase with insulin secretory granules has been shown by cell microscopy techniques. We used MIN6 insulin-secretory cells and organelle fractionation to determine the effects of glucose on the subcellular distribution of glucokinase. After permeabilization with digitonin,...

  • SUM0ylation Regulates Insulin Exocytosis Downstream of Secretory Granule Docking in Rodents and Humans. Xiao-Qing Dai; Plummer, Greg; Casimir, Marina; Youhou Kang; Hajmrle, Catherine; Gaisano, Herbert Y.; Manning Fox, Jocelyn E.; MacDonald, Patrick E. // Diabetes;Mar2011, Vol. 60 Issue 3, p838 

    OBJECTIVE--The reversible attachment of small ubiquitin-like modifier (SUMO) proteins controls target localization and function. We examined an acute role for the SUMOylation pathway in downstream events mediating insulin secretion. RESEARCH DESIGN AND METHODS--We studied islets and f3-cells...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics