Adelle Coster - Academia.edu (original) (raw)

Papers by Adelle Coster

Actin Tropomyosin Assembly Intermediates

Biophysical Journal, 2015

Coupling and Synchronization of Oscillators in the Sinoatrial Node

A receptor state space model of the insulin signalling system in glucose transport

Mathematical medicine and biology : a journal of the IMA, Jan 10, 2015

Insulin is a potent peptide hormone that regulates glucose levels in the blood. Insulin-sensitive... more Insulin is a potent peptide hormone that regulates glucose levels in the blood. Insulin-sensitive cells respond to insulin stimulation with the translocation of glucose transporter 4 (GLUT4) to the plasma membrane (PM), enabling the clearance of glucose from the blood. Defects in this process can give rise to insulin resistance and ultimately diabetes. One widely cited model of insulin signalling leading to glucose transport is that of Sedaghat et al. (2002) Am. J. Physiol. Endocrinol. Metab. 283: , E1084-E1101. Consisting of 20 deterministic ordinary differential equations (ODEs), it is the most comprehensive model of insulin signalling to date. However, the model possesses some major limitations, including the non-conservation of key components. In the current work, we detail mathematical and sensitivity analyses of the Sedaghat model. Based on the results of these analyses, we propose a reduced state space model of the insulin receptor subsystem. This reduced model maintains the ...

PLoS ONE, 2014

Background and Aims: L-glutamine is an efficacious glucagon-like peptide (GLP)-1 secretagogue in ... more Background and Aims: L-glutamine is an efficacious glucagon-like peptide (GLP)-1 secretagogue in vitro. When administered with a meal, glutamine increases GLP-1 and insulin excursions and reduces postprandial glycaemia in type 2 diabetes patients. The aim of the study was to assess the efficacy and safety of daily glutamine supplementation with or without the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin in well-controlled type 2 diabetes patients.

Glut4 is Sorted from a Rab10-Independent Constitutive Recycling Pathway into a Highly Insulin-Responsive Rab10-Dependent Sequestration Pathway after Adipocyte Differentiation

Journal of Biological Chemistry, 2015

The RabGAP AS160/TBC1D4 controls exocytosis of the insulin-sensitive glucose transporter Glut4 in... more The RabGAP AS160/TBC1D4 controls exocytosis of the insulin-sensitive glucose transporter Glut4 in adipocytes. Glut4 is internalized and recycled through a highly regulated secretory pathway in these cells. Glut4 also cycles through a slow constitutive endosomal pathway distinct from the fast transferrin (Tf) receptor recycling pathway. This slow constitutive pathway is the only Glut4 cycling pathway in undifferentiated fibroblasts. The α2-macroglobulin receptor LRP1 cycles with Glut4 and the Tf receptor, through all three exocytic pathways. To further characterize these pathways, the effects of knockdown of AS160 substrates on the trafficking kinetics of Glut4, LRP1, and the Tf receptor were measured in adipocytes and fibroblasts. Rab10 knockdown decreased cell surface Glut4 in insulin-stimulated adipocytes by 65%, but not in basal adipocytes or in fibroblasts. This decrease was due primarily to a 62% decrease in the rate constant of Glut4 exocytosis (kex), although Rab10 knockdown also caused a 1.4-fold increase in the rate constant of Glut4 endocytosis (ken). Rab10 knockdown in adipocytes also decreased cell surface LRP1 by 30% by decreasing kex 30-40%. There was no effect on LRP1 trafficking in fibroblasts, or on Tf receptor trafficking in either cell type. These data confirm that Rab10 is an AS160 substrate that limits exocytosis through the highly insulin-responsive specialized secretory pathway in adipocytes. They further show that the slow constitutive endosomal (fibroblast) recycling pathway is Rab10-independent. Thus, Rab10 is a marker for the specialized pathway in adipocytes. Interestingly, mathematical modeling shows that Glut4 traffics predominantly through the specialized, Rab10-dependent pathway both before and after insulin stimulation.

Dietary acid load, metabolic acidosis and insulin resistance - Lessons from cross-sectional and overfeeding studies in humans

Clinical nutrition (Edinburgh, Scotland), Jan 12, 2015

Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load... more Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load, a predictor of type 2 diabetes risk. The relationships between dietary acid load, mild metabolic acidosis and insulin resistance remain unclear. The objective of this study was to assess the association between dietary acid load, body acid/base markers and peripheral insulin resistance at baseline and following a short-term overfeeding intervention in healthy individuals. In a cross-sectional study of 104 men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Plasma lactate, a marker of metabolic acidosis, was assessed and acid load scores (potential renal acid load, PRAL and net endogenous acid production, NEAP) derived from diet diaries. The cohort was grouped into lean and overweight/obese and the latter further classified as insulin-sensitive (Obsen) and insulin-resistant (Obres) based on hyperinsulinemic-euglycemic clamp glucose infusion rate (GIR, t...

2005 IEEE Engineering in Medicine and Biology 27th Annual Conference, 2005

We investigate a new model for the cardiac system. It embodies the main features of cardiac activ... more We investigate a new model for the cardiac system. It embodies the main features of cardiac activity with great flexibility. It can be tuned to suit different cell types, and scaled up or down to represent either a single cell, an aggregate, or whole tissue. We demonstrate its use in the generation of a clinically realistic electrocardiogram (ECG) and other dynamical behaviours such as spiral waves. Our model is computationally economic -about 1000 times faster than ion conductance based models and is thus ideal for doing large scale simulations.

Methods in molecular biology (Clifton, N.J.), 2008

Recycling via the plasma membrane is a key feature that is shared by many membrane proteins. Usin... more Recycling via the plasma membrane is a key feature that is shared by many membrane proteins. Using a combination of indirect immunofluorescence labeling and fluorescence detection using a fluorescence multiwell plate reader, we exploited the possibilities of quantitatively measuring the trafficking kinetics of transmembrane proteins. Parameters that can be studied include dynamic appearance/presence at the cell surface, recycling via the cell surface, and internalization. For the insulin-responsive glucose transporter GLUT4 (glucose transporter number 4), details are presented on how to quantitatively measure insulin-induced GLUT4 translocation toward the plasma membrane (transition state) and to analyze cell surface recycling of GLUT4 in basal and insulin-stimulated cells (steady state).

Insulin Stimulates the Entry of GLUT4 into the Endosomal Recycling Pathway by a Quantal Mechanism

Traffic, 2004

The insulin-sensitive glucose transporter GLUT4 mediates the uptake of glucose into adipocytes an... more The insulin-sensitive glucose transporter GLUT4 mediates the uptake of glucose into adipocytes and muscle cells. In this study we have used a novel 96-well plate fluorescence assay to study the kinetics of GLUT4 trafficking in 3T3-L1 adipocytes. We have found evidence for a graded release mechanism whereby GLUT4 is released into the plasma membrane recycling system in a nonkinetic manner as follows: the kinetics of appearance of GLUT4 at the plasma membrane is independent of the insulin concentration; a large proportion of GLUT4 molecules do not participate in plasma membrane recycling in the absence of insulin; and with increasing insulin there is an incremental increase in the total number of GLUT4 molecules participating in the recycling pathway rather than simply an increased rate of recycling. We propose a model whereby GLUT4 is stored in a compartment that is disengaged from the plasma membrane recycling system in the basal state. In response to insulin, GLUT4 is quantally released from this compartment in a pulsatile manner, leaving some sequestered from the recycling pathway even in conditions of excess insulin. Once disengaged from this location we suggest that in the continuous presence of insulin this quanta of GLUT4 continuously recycles to the plasma membrane, possibly via non-endosomal carriers that are formed at the perinuclear region.

Noise accelerates synchronization of coupled nonlinear oscillators

Physical Review E, 2006

For a chain of homogeneous nonlinear oscillators starting from different initial phases, a certai... more For a chain of homogeneous nonlinear oscillators starting from different initial phases, a certain amount of time is required for the system to evolve to complete phase synchronization. The effect of independent noise in such a system was investigated, and an optimal noise intensity was found that minimized the average synchronization time. Both threshold noise and connection noise show similar effects. The features of the phenomenon and the underlying mechanism are discussed through the analysis of a two-unit system and the numerical studies of chains up to 30 units in length.

Molecular and Cellular Biology, 2004

The insulin-responsive glucose transporter GLUT4 plays an essential role in glucose homeostasis. ... more The insulin-responsive glucose transporter GLUT4 plays an essential role in glucose homeostasis. A novel assay was used to study GLUT4 trafficking in 3T3-L1 fibroblasts/preadipocytes and adipocytes. Whereas insulin stimulated GLUT4 translocation to the plasma membrane in both cell types, in nonstimulated fibroblasts GLUT4 readily cycled between endosomes and the plasma membrane, while this was not the case in adipocytes. This efficient retention in basal adipocytes was mediated in part by a C-terminal targeting motif in GLUT4. Insulin caused a sevenfold increase in the amount of GLUT4 molecules present in a trafficking cycle that included the plasma membrane. Strikingly, the magnitude of this increase correlated with the insulin dose, indicating that the insulin-induced appearance of GLUT4 at the plasma membrane cannot be explained solely by a kinetic change in the recycling of a fixed intracellular GLUT4 pool. These data are consistent with a model in which GLUT4 is present in a storage compartment, from where it is released in a graded or quantal manner upon insulin stimulation and in which released GLUT4 continuously cycles between intracellular compartments and the cell surface independently of the nonreleased pool.

Insulin-Regulated Glut4 Translocation: Membrane Protein Trafficking With Six Distinctive Steps

Journal of Biological Chemistry, 2014

The trafficking kinetics of Glut4, the transferrin (Tf) receptor, and LRP1 were quantified in adi... more The trafficking kinetics of Glut4, the transferrin (Tf) receptor, and LRP1 were quantified in adipocytes and undifferentiated fibroblasts. Six steps were identified that determine steady state cell surface Glut4: (i) endocytosis, (ii) degradation, (iii) sorting, (iv) sequestration, (v) release, and (vi) tethering/docking/fusion. Endocytosis of Glut4 is 3 times slower than the Tf receptor in fibroblasts (ken = 0.2 min(-1) versus 0.6 min(-1)). Differentiation decreases Glut4 ken 40% (ken = 0.12 min(-1)). Differentiation also decreases Glut4 degradation, increasing total and cell surface Glut4 3-fold. In fibroblasts, Glut4 is recycled from endosomes through a slow constitutive pathway (kex = 0.025-0.038 min(-1)), not through the fast Tf receptor pathway (kex = 0.2 min(-1)). The kex measured in adipocytes after insulin stimulation is similar (kex = 0.027 min(-1)). Differentiation decreases the rate constant for sorting into the Glut4 recycling pathway (ksort) 3-fold. In adipocytes, Glut4 is also sorted from endosomes into a second exocytic pathway through Glut4 storage vesicles (GSVs). Surprisingly, transfer from endosomes into GSVs is highly regulated; insulin increases the rate constant for sequestration (kseq) 8-fold. Release from sequestration in GSVs is rate-limiting for Glut4 exocytosis in basal adipocytes. AS160 regulates this step. Tethering/docking/fusion of GSVs to the plasma membrane is regulated through an AS160-independent process. Insulin increases the rate of release and fusion of GSVs (kfuseG) 40-fold. LRP1 cycles with the Tf receptor and Glut4 in fibroblasts but predominantly with Glut4 after differentiation. Surprisingly, AS160 knockdown accelerated LRP1 exocytosis in basal and insulin-stimulated adipocytes. These data indicate that AS160 may regulate trafficking into as well as release from GSVs.

Automatic identification of fusion events in TIRF microscopy image sequences

2009 IEEE 12th International Conference on Computer Vision Workshops, ICCV Workshops, 2009

Page 1. Abstract This paper presents a novel computer vision system for automated identification ... more Page 1. Abstract This paper presents a novel computer vision system for automated identification of vesicle-plasma membrane fusion events in image sequences obtained from Total Internal Reflection Fluorescence (TIRF) microscopes. ...

Obese, yet insulin sensitive humans

Obesity Research & Clinical Practice, 2011

Impaired Akt phosphorylation in insulin-resistant human muscle is accompanied by selective and heterogeneous downstream defects

Diabetologia, 2013

Muscle insulin resistance, one of the earliest defects associated with type 2 diabetes, involves ... more Muscle insulin resistance, one of the earliest defects associated with type 2 diabetes, involves changes in the phosphoinositide 3-kinase/Akt network. The relative contribution of obesity vs insulin resistance to perturbations in this pathway is poorly understood. We used phosphospecific antibodies against targets in the Akt signalling network to study insulin action in muscle from lean, overweight/obese and type 2 diabetic individuals before and during a hyperinsulinaemic-euglycaemic clamp. Insulin-stimulated Akt phosphorylation at Thr309 and Ser474 was highly correlated with whole-body insulin sensitivity. In contrast, impaired phosphorylation of Akt substrate of 160 kDa (AS160; also known as TBC1D4) was associated with adiposity, but not insulin sensitivity. Neither insulin sensitivity nor obesity was associated with defective insulin-dependent phosphorylation of forkhead box O (FOXO) transcription factor. In view of the resultant basal hyperinsulinaemia, we predicted that this selective response within the Akt pathway might lead to hyperactivation of those processes that were spared. Indeed, the expression of genes targeted by FOXO was downregulated in insulin-resistant individuals. These results highlight non-linearity in Akt signalling and suggest that: (1) the pathway from Akt to glucose transport is complex; and (2) pathways, particularly FOXO, that are not insulin-resistant, are likely to be hyperactivated in response to hyperinsulinaemia. This facet of Akt signalling may contribute to multiple features of the metabolic syndrome.

1st IEEE Workshop on Video-Oriented Object and Event Classification

1st IEEE Workshop on Video-Oriented Object and Event Classification ... Organizers: Shuicheng Yan... more 1st IEEE Workshop on Video-Oriented Object and Event Classification ... Organizers: Shuicheng Yan, Qingshan Liu, Changsheng Xu Date: Monday, September 28, 2009, 9:30-17:15 ... Session 1: Action Recognition Effective Codebooks for Human Action Categorization Lamberto Ballan, Marco Bertini, Alberto Del Bimbo, Lorenzo Seidenari, Giuseppe Serra Trajectons: Action Recognition Through the Motion Analysis of Tracked Features Pyry Matikainen, Martial Hebert, Rahul Sukthankar Human Action Detection by Boosting Efficient Motion Features ...