Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The first luminal loop confers insulin responsiveness to glucose transporter 4.

ABSTRACT: Glucose transporter isoform 4 (GLUT4), is the sole glucose transporter responsible for the effect of insulin on postprandial blood glucose clearance. However, the nature of the insulin sensitivity of GLUT4 remains unknown. In this study, we replaced the first luminal loop of cellugyrin, a 4-transmembrane protein that does not respond to insulin, with that of GLUT4. The chimera protein is targeted to the intracellular insulin-responsive vesicles and is translocated to the plasma membrane upon insulin stimulation. The faithful targeting of the chimera depends on the expression of the sorting receptor sortilin, which interacts with the unique amino acid residues in the first luminal loop of GLUT4. Thus the first luminal loop may confer insulin responsiveness to the GLUT4 molecule.

SUBMITTER: Kim JY

PROVIDER: S-EPMC3290648 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The first luminal loop confers insulin responsiveness to glucose transporter 4.

Kim Ju Youn JY Kandror Konstantin V KV

Molecular biology of the cell 20120119 5

Glucose transporter isoform 4 (GLUT4), is the sole glucose transporter responsible for the effect of insulin on postprandial blood glucose clearance. However, the nature of the insulin sensitivity of GLUT4 remains unknown. In this study, we replaced the first luminal loop of cellugyrin, a 4-transmembrane protein that does not respond to insulin, with that of GLUT4. The chimera protein is targeted to the intracellular insulin-responsive vesicles and is translocated to the plasma membrane upon ins ...[more]

PMID: 22262463

Similar Datasets

Insulin responsiveness in skeletal muscle is determined by glucose transporter (Glut4) protein level.

Project description:Glucose transport in skeletal muscle is mediated by two distinct transporter isoforms, designated muscle/adipose glucose transporter (Glut4) and erythrocyte/HepG2/brain glucose transporter (Glut1), which differ in both abundance and membrane distribution. The present study was designed to investigate whether differences in insulin responsiveness of red and white muscle might be due to differential expression of the glucose transporter isoforms. Glucose transport, as well as Glut1 and Glut4 protein and mRNA levels, were determined in red and white portions of the quadriceps and gastrocnemius muscles of male Sprague-Dawley rats (body wt. approx. 250 g). Maximal glucose transport (in response to 100 nM-insulin) in the perfused hindlimb was 3.6 times greater in red than in white muscle. Red muscle contained approx. 5 times more total Glut4 protein and 2 times more Glut4 mRNA than white muscle, but there were no differences in the Glut1 protein or mRNA levels between the fibre types. Our data indicate that differences in responsiveness of glucose transport in specific skeletal muscle fibre types may be dependent upon the amount of Glut4 protein. Because this protein plays such an integral part in glucose transport in skeletal muscle, any impairment in its expression may play a role in insulin resistance.

| S-EPMC1131735 | biostudies-other

Insulin responsiveness of glucose transporter 4 in 3T3-L1 cells depends on the presence of sortilin.

Project description:Insulin-dependent translocation of glucose transporter 4 (Glut4) to the plasma membrane of fat and skeletal muscle cells plays the key role in postprandial clearance of blood glucose. Glut4 represents the major cell-specific component of the insulin-responsive vesicles (IRVs). It is not clear, however, whether the presence of Glut4 in the IRVs is essential for their ability to respond to insulin stimulation. We prepared two lines of 3T3-L1 cells with low and high expression of myc7-Glut4 and studied its translocation to the plasma membrane upon insulin stimulation, using fluorescence-assisted cell sorting and cell surface biotinylation. In undifferentiated 3T3-L1 preadipocytes, translocation of myc7-Glut4 was low regardless of its expression levels. Coexpression of sortilin increased targeting of myc7-Glut4 to the IRVs, and its insulin responsiveness rose to the maximal levels observed in fully differentiated adipocytes. Sortilin ectopically expressed in undifferentiated cells was translocated to the plasma membrane regardless of the presence or absence of myc7-Glut4. AS160/TBC1D4 is expressed at low levels in preadipocytes but is induced in differentiation and provides an additional mechanism for the intracellular retention and insulin-stimulated release of Glut4.

| S-EPMC3784384 | biostudies-literature

Developing Insulin Delivery Devices with Glucose Responsiveness.

Project description:Individuals with type 1 and advanced type 2 diabetes require daily insulin therapy to maintain blood glucose levels in normoglycemic ranges to prevent associated morbidity and mortality. Optimal insulin delivery should offer both precise dosing in response to real-time blood glucose levels as well as a feasible and low-burden administration route to promote long-term adherence. A series of glucose-responsive insulin delivery mechanisms and devices have been reported to increase patient compliance while mitigating the risk of hypoglycemia. This review discusses currently available insulin delivery devices, overviews recent developments towards the generation of glucose-responsive delivery systems, and provides commentary on the opportunities and barriers ahead regarding the integration and translation of current glucose-responsive insulin delivery designs.

| S-EPMC7758938 | biostudies-literature

Glucose tolerance and insulin responsiveness in Gitelman syndrome patients.

Project description:OBJECTIVE:Impaired glucose metabolism and insulin sensitivity have been reported in patients with Gitelman syndrome (GS), but insulin secretion and the related mechanisms are not well understood. DESIGN AND METHODS:The serum glucose levels, insulin secretion and insulin sensitivity were evaluated in patients with GS (n?=?28), patients with type 2 diabetes mellitus (DM) and healthy individuals (n?=?20 in both groups) using an oral glucose tolerance test. Serum and urine sodium, potassium and creatinine levels were measured at 0, 30, 60, 120 and 180?min after an oral glucose load was administered. RESULTS:The areas under the serum glucose curves were higher in the GS patients than those in the healthy controls (17.4?±?5.1?mmol·h/L vs 14.5?±?2.8?mmol·h/L, P?=?0.02) but lower than those in the DM patients (24.8?±?5.3?mmol·h/L, P?<?0.001). The areas under the serum insulin curves and the insulin secretion indexes in GS patients were higher than those in DM patients and lower than those in healthy subjects. The insulin secretion-sensitivity index of GS patients was between that of healthy subjects and DM patients, but the insulin sensitivity indices were not different among the three groups. After one hour of glucose administration, the serum potassium level significantly decreased from baseline, and the urinary potassium-to-creatinine ratio increased gradually and peaked at 2?h. CONCLUSIONS:Glucose metabolism and insulin secretion were impaired in GS patients, but insulin sensitivity was comparable between GS patients and patients with type 2 DM. After administration of an oral glucose load, the plasma potassium level decreased in GS patients due to the increased excretion of potassium in the urine.

| S-EPMC5632718 | biostudies-literature

Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia.

Project description:Insulin therapy in the setting of type 1 and advanced type 2 diabetes is complicated by increased risk of hypoglycemia. This potentially fatal complication could be mitigated by a glucose-responsive insulin analog. We report an insulin-facilitated glucose transporter (Glut) inhibitor conjugate, in which the insulin molecule is rendered glucose-responsive via conjugation to an inhibitor of Glut. The binding affinity of this insulin analog to endogenous Glut is modulated by plasma and tissue glucose levels. In hyperglycemic conditions (e.g., uncontrolled diabetes or the postprandial state), the in situ-generated insulin analog-Glut complex is driven to dissociate, freeing the insulin analog and glucose-accessible Glut to restore normoglycemia. Upon overdose, enhanced binding of insulin analog to Glut suppresses the glucose transport activity of Glut to attenuate further uptake of glucose. We demonstrate the ability of this insulin conjugate to regulate blood glucose levels within a normal range while mitigating the risk of hypoglycemia in a type 1 diabetic mouse model.

| S-EPMC6561193 | biostudies-literature

A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery.

Project description:Insulin administration for the management of diabetes is accompanied by hypoglycemia, which is expected to be mitigated by glucose-responsive smart insulin that has self-regulation ability in response to blood glucose level (BGL) fluctuation. Here, we have prepared a new insulin analog by modifying insulin with forskolin (designated as insulin-F), a glucose-transporter (Glut) inhibitor. In vitro, insulin-F is capable of binding to Glut on erythrocyte ghosts, which can be inhibited by glucose and cytochalasin B. Upon subcutaneous injection in type 1 diabetic mice, insulin-F maintains BGLs below 200 mg mL-1 for up to 10 h, and achieves 20 h with two sequential injections. Moreover, insulin-F also binds to endogenous Gluts. Upon a glucose challenge, the elevated level of glucose competitively replaces and liberates insulin-F that binds to Glut, rapidly restoring BGLs to the normal range.

| S-EPMC7148115 | biostudies-literature

Zinc Finger Protein 407 (ZFP407) Regulates Insulin-Stimulated Glucose Uptake and Glucose Transporter 4 (Glut4) mRNA

Project description:Using RNA-Seq, we compared the transcriptomes of differentiated 3T3-L1 adipocytes for control and ZFP407-deficient cells

2015-01-16 | GSE64757 | GEO

Proportional Insulin Infusion in Closed-Loop Control of Blood Glucose.

Project description:A differential equation model is formulated that describes the dynamics of glucose concentration in blood circulation. The model accounts for the intake of food, expenditure of calories and the control of glucose levels by insulin and glucagon. These and other hormones affect the blood glucose level in various ways. In this study only main effects are taken into consideration. Moreover, by making a quasi-steady state approximation the model is reduced to a single nonlinear differential equation of which parameters are fit to data from healthy subjects. Feedback provided by insulin plays a key role in the control of the blood glucose level. Reduced β-cell function and insulin resistance may hamper this process. With the present model it is shown how by closed-loop control these defects, in an organic way, can be compensated with continuous infusion of exogenous insulin.

| S-EPMC5217952 | biostudies-literature

Intra-islet glucagon confers β-cell glucose competence for first-phase insulin secretion and favors GLP-1R stimulation by exogenous glucagon.

Project description:We report that intra-islet glucagon secreted from α-cells signals through β-cell glucagon and GLP-1 receptors (GcgR and GLP-1R), thereby conferring to rat islets their competence to exhibit first-phase glucose-stimulated insulin secretion (GSIS). Thus, in islets not treated with exogenous glucagon or GLP-1, first-phase GSIS is abolished by a GcgR antagonist (LY2786890) or a GLP-1R antagonist (Ex[9-39]). Mechanistically, glucose competence in response to intra-islet glucagon is conditional on β-cell cAMP signaling because it is blocked by the cAMP antagonist prodrug Rp-8-Br-cAMPS-pAB. In its role as a paracrine hormone, intra-islet glucagon binds with high affinity to the GcgR, while also exerting a "spillover" effect to bind with low affinity to the GLP-1R. This produces a right shift of the concentration-response relationship for the potentiation of GSIS by exogenous glucagon. Thus, 0.3 nM glucagon fails to potentiate GSIS, as expected if similar concentrations of intra-islet glucagon already occupy the GcgR. However, 10 to 30 nM glucagon effectively engages the β-cell GLP-1R to potentiate GSIS, an action blocked by Ex[9-39] but not LY2786890. Finally, we report that the action of intra-islet glucagon to support insulin secretion requires a step-wise increase of glucose concentration to trigger first-phase GSIS. It is not measurable when GSIS is stimulated by a gradient of increasing glucose concentrations, as occurs during an oral glucose tolerance test in vivo. Collectively, such findings are understandable if defective intra-islet glucagon action contributes to the characteristic loss of first-phase GSIS in an intravenous glucose tolerance test, that is, diagnostic of type 2 diabetes in the clinical setting.

| S-EPMC8789663 | biostudies-literature

Zinc Finger Protein 407 (ZFP407) Regulates Insulin-Stimulated Glucose Uptake and Glucose Transporter 4 (Glut4) mRNA

Project description:Using RNA-Seq, we compared the transcriptomes of differentiated 3T3-L1 adipocytes for control and ZFP407-deficient cells Differentiated 3T3-L1 cells were electroporated with control or 1 of 2 Zfp407 siRNAs. Six independent siRNA electroporations were conducted for the control siRNA and 3 independent electroporations were conducted for each Zfp407 siRNA.

2015-01-16 | E-GEOD-64757 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data