Insulin Regulated Trafficking of Glucose Transporter 4: A Kinetic Perspective
type: CreativeWork
description: Regulation of blood glucose homeostasis is a critical process; defects in this process can lead to insulin resistance, type II diabetes, and metabolic syndrome. Glucose homeostasis is regulated in part by insulin action on peripheral tissues, especially muscle, fat, and the liver. In muscle and adipose tissue, insulin increases glucose transport by increasing the amount of glucose transporter isoform 4 (Glut4) in the plasma membrane by recruiting the transporter from intracellular storage depots. Insulin regulation of Glut4 trafficking has been extensively studied, and although Glut4 partially overlaps with the general trafficking pathways, it is uniquely regulated by insulin. Few studies have determined if experimental perturbations to the system affect important rate-limiting regulatory steps unique to the trafficking of Glut4. Our lab has developed a series of high-throughput quantitative flow cytometric methods for analytical measurement of Glut4 trafficking kinetics. In order to provide mechanistic information about the roles of proteins regulating Glut4 traffic, we used these methods to develop trafficking assays for Glut4 in addition to other well characterized markers of general endosomal pathways. We demonstrated that insulin promotes Glut4 translocation by increasing the exocytosis of Glut4 and releasing Glut4 from basal storage compartments. We illustrated that insulin does not regulate the rate of Glut4 endocytosis and demonstrated that previously measured decreases of endocytosis may be an artifact of ignoring the effects of exocytosis on internalization assays. We also showed that Glut4 traffics very differently from a marker of the early endosomal pathway and similarly to a late endosomal marker. In order to identify important regulatory mechanisms expressed in adipocytes, we characterized trafficking of the three endosomal proteins in undifferentiated fibroblasts as well as in adipocytes, and identified the minimum number of regulatory steps required…
abstract: Regulation of blood glucose homeostasis is a critical process; defects in this process can lead to insulin resistance, type II diabetes, and metabolic syndrome. Glucose homeostasis is regulated in part by insulin action on peripheral tissues, especially muscle, fat, and the liver. In muscle and adipose tissue, insulin increases glucose transport by increasing the amount of glucose transporter isoform 4 (Glut4) in the plasma membrane by recruiting the transporter from intracellular storage depots. Insulin regulation of Glut4 trafficking has been extensively studied, and although Glut4 partially overlaps with the general trafficking pathways, it is uniquely regulated by insulin. Few studies have determined if experimental perturbations to the system affect important rate-limiting regulatory steps unique to the trafficking of Glut4. Our lab has developed a series of high-throughput quantitative flow cytometric methods for analytical measurement of Glut4 trafficking kinetics. In order to provide mechanistic information about the roles of proteins regulating Glut4 traffic, we used these methods to develop trafficking assays for Glut4 in addition to other well characterized markers of general endosomal pathways. We demonstrated that insulin promotes Glut4 translocation by increasing the exocytosis of Glut4 and releasing Glut4 from basal storage compartments. We illustrated that insulin does not regulate the rate of Glut4 endocytosis and demonstrated that previously measured decreases of endocytosis may be an artifact of ignoring the effects of exocytosis on internalization assays. We also showed that Glut4 traffics very differently from a marker of the early endosomal pathway and similarly to a late endosomal marker. In order to identify important regulatory mechanisms expressed in adipocytes, we characterized trafficking of the three endosomal proteins in undifferentiated fibroblasts as well as in adipocytes, and identified the minimum number of regulatory steps required…
author: Brewer, Paul D.
keywords: endocytosis, exocytosis, Glut4, Insulin, mathematical modeling, membrane trafficking
date published: 2013
date modified: 2026-07-27T21:47:14Z
provider: University of Nevada - Reno
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Nevada - Reno

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11714/3114