Comparative effects of IGF-I and insulin on the glucose transporter system in rat muscle

1994 ◽  
Vol 267 (3) ◽  
pp. E461-E466 ◽  
Author(s):  
S. Lund ◽  
A. Flyvbjerg ◽  
G. D. Holman ◽  
F. S. Larsen ◽  
O. Pedersen ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Acute Effect ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Glut 4 ◽  
Igf I ◽  
Glut 4 Translocation

The acute effect of insulin-like growth factor I (IGF-I) and insulin on glucose uptake and the glucose transport system in in vitro incubated rat soleus muscles was examined using 3-O-methylglucose and the ATB-[3H]BMPA exofacial photolabeling technique. IGF-I and insulin both stimulated 3-O-methylglucose uptake and GLUT-4 translocation in a dose-dependent manner with a maximal effect six- to sevenfold above basal. No additive effects of IGF-I and insulin on maximal 3-O-methylglucose uptake were found. On a molar basis, IGF-I was 13 times less potent than insulin. Receptor binding experiments showed that IGF-I exhibited a much lower affinity for the insulin receptor [half-maximal effective dose (ED50) = 28.5 nM] than that of insulin (ED50 = 0.20 nM). In contrast, IGF-I bound to the partially purified IGF-I receptor with an apparent affinity (ED50 = 3.7 nM) that was similar to the concentrations of IGF-I which caused half-maximal activation of 3-O-methylglucose uptake (ED50 = 2.4 nM) and GLUT-4 translocation (ED50 = 2.5 nM). Our findings suggest that IGF-I exerts its insulin-like effects on glucose uptake primarily through its own specific receptor and that the molecular events underlying IGF-I and insulin actions on glucose uptake in skeletal muscle are similar, namely caused by a translocation of the GLUT-4 transporter from an intracellular pool to the cell surface.

scholarly journals Sphingomyelinase has an insulin-like effect on glucose transporter translocation in adipocytes

1998 ◽  
Vol 274 (5) ◽  
pp. R1446-R1453 ◽  
Author(s):  
T. S. David ◽  
P. A. Ortiz ◽  
T. R. Smith ◽  
J. Turinsky
Keyword(s):  
Plasma Membrane ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Insulin Signaling Pathway ◽  
Glut 1 ◽  
Glut 4 ◽  
Glut 4 Translocation

Rat epididymal adipocytes were incubated with 0, 0.1, and 1 mU sphingomyelinase/ml for 30 or 60 min, and glucose uptake and GLUT-1 and GLUT-4 translocation were assessed. Adipocytes exposed to 1 mU sphingomyelinase/ml exhibited a 173% increase in glucose uptake. Sphingomyelinase had no effect on the abundance of GLUT-1 in the plasma membrane of adipocytes. In contrast, 1 mU sphingomyelinase/ml increased plasma membrane content of GLUT-4 by 120% and produced a simultaneous decrease in GLUT-4 abundance in the low-density microsomal fraction. Sphingomyelinase had no effect on tyrosine phosphorylation of either the insulin receptor β-subunit or the insulin receptor substrate-1, a signaling molecule in the insulin signaling pathway. It is concluded that the incubation of adipocytes with sphingomyelinase results in insulin-like translocation of GLUT-4 to the plasma membrane and that this translocation does not occur via the activation of the initial components of the insulin signaling pathway.

Phenylarsine oxide inhibits insulin-stimulated protein phosphatase 1 activity and GLUT-4 translocation

1994 ◽  
Vol 267 (1) ◽  
pp. E14-E23 ◽  
Author(s):  
N. Begum
Keyword(s):  
Protein Phosphatase ◽  
Glucose Transporter ◽  
Insulin Binding ◽  
Protein Phosphatase 1 ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Phenylarsine Oxide ◽  
Insulin Signal Transduction ◽  
Glut 4 ◽  
Glut 4 Translocation

Phenylarsine oxide (PAO) has previously been shown to inhibit insulin-stimulated glucose transport without affecting insulin binding and tyrosine kinase activity of insulin receptor (S. C. Frost and M. D. Lane. J. Biol. Chem. 260: 2646-2652, 1985). This study examines the effect of PAO on insulin's ability to activate adipocyte protein phosphatase 1 (PP-1) and dephosphorylate GLUT-4, the insulin-sensitive glucose transporter. In particulate fractions, insulin stimulated PP-1 activity (40% increase over basal with phosphorylase a) in a time- and dose-dependent manner (half-maximal effect of 0.89 nM in 1 min). Insulin did not alter cytosolic PP-1 activity. With GLUT-4 as a substrate, insulin caused more than twofold stimulation of particulate PP-1 activity. Addition of PAO (5 microM) before or after insulin treatment abolished insulin's effect on PP-1 activation. The presence of 2,3-dimercaptopropanol (200 microM) prevented the effect of PAO on PP-1 activation and glucose uptake. In addition, PAO significantly increased GLUT-4 phosphorylation, blocked insulin-stimulated dephosphorylation, and partially diminished insulin-stimulated translocation of GLUT-4. We conclude that PAO may interfere with the components of insulin signal transduction pathways that lead to the activation of PP-1 and this may be responsible for the observed inhibition in insulin action.

scholarly journals Ginsenoside Rb1 stimulates glucose uptake through insulin-like signaling pathway in 3T3-L1 adipocytes

2008 ◽  
Vol 198 (3) ◽  
pp. 561-569 ◽  
Author(s):  
Wenbin Shang ◽  
Ying Yang ◽  
Libin Zhou ◽  
Boren Jiang ◽  
Hua Jin ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Glucose Transport ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
C2c12 Myotubes ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Active Constituent

A series of clinical trials and animal experiments have demonstrated that ginseng and its major active constituent, ginsenosides, possess glucose-lowering action. In our previous study, ginsenoside Rb1 has been shown to regulate peroxisome proliferator-activated receptor γ activity to facilitate adipogenesis of 3T3-L1 cells. However, the effect of Rb1 on glucose transport in insulin-sensitive cells and its molecular mechanism need further elucidation. In this study, Rb1 significantly stimulated basal and insulin-mediated glucose uptake in a time- and dose-dependent manner in 3T3-L1 adipocytes and C2C12 myotubes; the maximal effect was achieved at a concentration of 1 μM and a time of 3 h. In adipocytes, Rb1 promoted GLUT1 and GLUT4 translocations to the cell surface, which was examined by analyzing their distribution in subcellular membrane fractions, and enhanced translocation of GLUT4 was confirmed using the transfection of GLUT4-green fluorescence protein in Chinese Hamster Ovary cells. Meanwhile, Rb1 increased the phosphorylation of insulin receptor substrate-1 and protein kinase B (PKB), and stimulated phosphatidylinositol 3-kinase (PI3K) activity in the absence of the activation of the insulin receptor. Rb1-induced glucose uptake as well as GLUT1 and GLUT4 translocations was inhibited by the PI3K inhibitor. These results suggest that ginsenoside Rb1 stimulates glucose transport in insulin-sensitive cells by promoting translocations of GLUT1 and GLUT4 by partially activating the insulin signaling pathway. These findings are useful in understanding the hypoglycemic and anti-diabetic properties of ginseng and ginsenosides.

Di(2-ethylhexyl)phthalate exposure impairs insulin receptor and glucose transporter 4 gene expression in L6 myotubes

2013 ◽  
Vol 33 (7) ◽  
pp. 685-700 ◽  
Author(s):  
P Rajesh ◽  
K Balasubramanian
Keyword(s):  
Gene Expression ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Negative Influence ◽  
Receptor Protein ◽  
Dependent Manner ◽  
L6 Myotubes ◽  
Dose Dependent

Di(2-ethyl hexyl)-phthalate (DEHP) is an endocrine disrupter and is the most abundantly used phthalate derivative, which is suspected to be an inevitable environmental exposure contributing to the increasing incidence of type-2 diabetes in humans. Therefore, the present study was designed to address the dose-dependent effects of DEHP on insulin signaling molecules in L6 myotubes. L6 myotubes were exposed to different concentrations (25, 50, and 100 μM) of DEHP for 24 h. At the end of exposure, cells were utilized for assessing various parameters. Insulin receptor and glucose transporter4 (GLUT4) gene expression, insulin receptor protein concentration, glucose uptake and oxidation, and enzymatic and nonenzymatic antioxidants were significantly reduced, but glutamine fructose-6-phosphate amidotransferase, nitric oxide, lipid peroxidation, and reactive oxygen species levels were elevated in a dose-dependent manner in L6 myotubes exposed to DEHP. The present study in turn shows the direct adverse effect of DEHP on the expression of insulin receptor and GLUT4 gene, glucose uptake, and oxidation in L6 myotubes suggesting that DEHP exposure may have a negative influence on insulin signaling.

scholarly journals Action of Metformin on the Insulin-Signaling Pathway and on Glucose Transport in Human Granulosa Cells

2011 ◽  
Vol 25 (2) ◽  
pp. 373-374
Author(s):  
Suman Rice ◽  
Laura Pellatt ◽  
Stacey Bryan ◽  
Saffron Ann Whitehead ◽  
Helen Diane Mason
Keyword(s):  
Insulin Receptor ◽  
Glucose Uptake ◽  
Granulosa Cells ◽  
Glucose Transporter ◽  
Polycystic Ovary ◽  
Mrna Levels ◽  
Insulin Sensitizer ◽  
Insulin Resistant ◽  
Glut 4 ◽  
Increase Glucose Uptake

Abstract Context: Hyperinsulinemia in polycystic ovary syndrome is widely treated with the insulin sensitizer metformin, which, in addition to its systemic effects, directly affects the ovarian insulin-stimulated steroidogenesis pathway. Objective: Our aim was to investigate the interaction of metformin with the other insulin-stimulated ovarian pathway, namely that leading to glucose uptake. Design: Human granulosa-luteal cells were cultured with metformin (10−7m), insulin (10 ng/ml) or metformin and insulin (Met + Ins) combined. Insulin receptor (IR) involvement was assessed by culture with an (anti)-insulin receptor (IR) antibody. Main Outcome Measures: The effect of metformin on insulin-receptor substrate proteins 1 and 2 (IRS-1 and -2) mRNA and protein expression was determined. The KGN granulosa-cell line was used to investigate the effect of insulin and metformin on Akt activation and glucose transporter-4 (Glut-4) expression. Glut-4 translocation from the cytosol to the membrane was determined in cytoplasmic and membrane-enriched fractions of protein lysates. Results: IRS-1 mRNA and protein increased with all treatments. In contrast, basal IRS-2 mRNA levels were barely detectable, but transcription was up-regulated by metformin. The anti-IR antibody reduced treatment-stimulated IRS-1 to basal levels and IRS-2 expression to an even greater extent than IRS-1, showing greater dependence on the IR than IRS-1. Metformin in the presence of insulin activated Akt and this was dependent on phosphoinositide-3 kinase, as was translocation of Glut-4 to the membrane. Metformin was able to substantially enhance the insulin-stimulated translocation of Glut-4 transporters from the cytosol to the membrane. Conclusion: This net increase in Glut-4 transporters in the plasma membrane has the potential to increase glucose uptake and metabolism by granulosa cells of the insulin-resistant polycystic ovary, thereby facilitating follicle growth.

Interleukin-1β Stimulates Glucose Uptake of Human Peritoneal Mesothelial Cells In Vitro

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 58-60 ◽  
Author(s):  
Michael Kruse ◽  
Arezki Mahiout ◽  
Volker Kliem ◽  
Peter Kurz ◽  
Karl-Martin Koch ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Interleukin 1 ◽  
Glucose Transporters ◽  
Mesothelial Cells ◽  
Dependent Manner ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells

To investigate whether the glucose uptake (GU) of human peritoneal mesothelial cells (HPMC) is mediated by glucose transporters and whether this uptake is influenced by interleukin 1–β (IL-1β), we measured 2-deoxy-(3H)-GU of HPMC in vitro, after exposing the cells for different times (two and 12 hours) to increasing concentrations (0.1, 1.0, and 2.0 ng/mL) of IL-1 β. To exclude a noncarrier-mediated transport, GU was also tested in the presence of cytochalasin B. All experiments were performed in triplicate in the cells of two donors. Cytochalasin B inhibits GU of HPMC almost completely. GU of HPMC is not stimulated by insulin. GU is stimulated by IL-1 β in a dose-dependent manner. These data indicate a GU of HPMC, which is mediated by a glucose transporter and stimulated by IL-1 β. The increased uptake of glucose from the dialysate In patients with peritonitis may be mediated by a (cytokineinduced) increased activity of HPMC glucose transporters.

Glucose uptake and glucose transporter proteins in skeletal muscle from undernourished rats

2001 ◽  
Vol 281 (5) ◽  
pp. E1101-E1109 ◽  
Author(s):  
María Agote ◽  
Luis Goya ◽  
Sonia Ramos ◽  
Carmen Alvarez ◽  
M. Lucía Gavete ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Subcellular Fractionation ◽  
Phosphatidylinositol 3 Kinase ◽  
Glut 4 ◽  
Gastrocnemius Muscles ◽  
Glucose Transporter Proteins ◽  
And Control

Undernutrition in rats impairs secretion of insulin but maintains glucose normotolerance, because muscle tissue presents an increased insulin-induced glucose uptake. We studied glucose transporters in gastrocnemius muscles from food-restricted and control anesthetized rats under basal and euglycemic hyperinsulinemic conditions. Muscle membranes were prepared by subcellular fractionation in sucrose gradients. Insulin-induced glucose uptake, estimated by a 2-deoxyglucose technique, was increased 4- and 12-fold in control and food-restricted rats, respectively. Muscle insulin receptor was increased, but phosphotyrosine-associated phosphatidylinositol 3-kinase activity stimulated by insulin was lower in undernourished rats, whereas insulin receptor substrate-1 content remained unaltered. The main glucose transporter in the muscle, GLUT-4, was severely reduced albeit more efficiently translocated in response to insulin in food-deprived rats. GLUT-1, GLUT-3, and GLUT-5, minor isoforms in skeletal muscle, were found increased in food-deprived rats. The rise in these minor glucose carriers, as well as the improvement in GLUT-4 recruitment, is probably insufficient to account for the insulin-induced increase in the uptake of glucose in undernourished rats, thereby suggesting possible changes in other steps required for glucose metabolism.

scholarly journals Genipin stimulates glucose transport in C2C12 myotubes via an IRS-1 and calcium-dependent mechanism

2012 ◽  
Vol 216 (3) ◽  
pp. 353-362 ◽  
Author(s):  
Chan-Juan Ma ◽  
Ai-Fang Nie ◽  
Zhi-Jian Zhang ◽  
Zhi-Guo Zhang ◽  
Li Du ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
C2c12 Myotubes ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Glut4 Translocation ◽  
Downstream Signaling ◽  
Calcium Dependent ◽  
Gardenia Jasminoides ◽  
Subcellular Membrane

Genipin, a compound derived from Gardenia jasminoides Ellis fruits, has been used over the years in traditional Chinese medicine to treat symptoms of type 2 diabetes. However, the molecular basis for its antidiabetic effect has not been fully revealed. In this study, we investigated the effects of genipin on glucose uptake and signaling pathways in C2C12 myotubes. Our study demonstrates that genipin stimulated glucose uptake in a time- and dose-dependent manner. The maximal effect was achieved at 2 h with a concentration of 10 μM. In myotubes, genipin promoted glucose transporter 4 (GLUT4) translocation to the cell surface, which was observed by analyzing their distribution in subcellular membrane fraction, and increased the phosphorylation of insulin receptor substrate-1 (IRS-1), AKT, and GSK3β. Meanwhile, genipin increased ATP levels, closed KATP channels, and then increased the concentration of calcium in the cytoplasm in C2C12 myotubes. Genipin-stimulated glucose uptake could be blocked by both the PI3-K inhibitor wortmannin and calcium chelator EGTA. Moreover, genipin increases the level of reactive oxygen species and ATP in C2C12 myotubes. These results suggest that genipin activates IRS-1, PI3-K, and downstream signaling pathway and increases concentrations of calcium, resulting in GLUT4 translocation and glucose uptake increase in C2C12 myotubes.

Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise

1998 ◽  
Vol 85 (4) ◽  
pp. 1218-1222 ◽  
Author(s):  
Polly A. Hansen ◽  
Lorraine A. Nolte ◽  
May M. Chen ◽  
John O. Holloszy
Keyword(s):  
Insulin Sensitivity ◽  
Cell Surface ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Glut 4 ◽  
Single Bout ◽  
Glut 4 Translocation ◽  
Muscle Glucose Transport

The purpose of this study was to determine whether the increase in insulin sensitivity of skeletal muscle glucose transport induced by a single bout of exercise is mediated by enhanced translocation of the GLUT-4 glucose transporter to the cell surface. The rate of 3- O-[3H]methyl-d-glucose transport stimulated by a submaximally effective concentration of insulin (30 μU/ml) was approximately twofold greater in the muscles studied 3.5 h after exercise than in those of the sedentary controls (0.89 ± 0.10 vs. 0.43 ± 0.05 μmol ⋅ ml−1 ⋅ 10 min−1; means ± SE for n = 6/group). GLUT-4 translocation was assessed by using the ATB-[2-3H]BMPA exofacial photolabeling technique. Prior exercise resulted in greater cell surface GLUT-4 labeling in response to submaximal insulin treatment (5.36 ± 0.45 dpm × 103/g in exercised vs. 3.00 ± 0.38 dpm × 103/g in sedentary group; n = 10/group) that closely mirrored the increase in glucose transport activity. The signal generated by the insulin receptor, as reflected in the extent of insulin receptor substrate-1 tyrosine phosphorylation, was unchanged after the exercise. We conclude that the increase in muscle insulin sensitivity of glucose transport after exercise is due to translocation of more GLUT-4 to the cell surface and that this effect is not due to potentiation of insulin-stimulated tyrosine phosphorylation.

Mobilization of GLUT-4 from intracellular vesicles by insulin and K+ depolarization in cultured H9c2 myotubes

1999 ◽  
Vol 277 (2) ◽  
pp. E259-E267 ◽  
Author(s):  
Bo Yu ◽  
Laurie A. Poirier ◽  
Laura E. Nagy
Keyword(s):  
Cell Surface ◽  
Glucose Uptake ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Phosphatidylinositol 3 Kinase ◽  
Glut 4 ◽  
Signaling Mechanisms ◽  
Increase Glucose Uptake ◽  
Glut 4 Translocation ◽  
Intracellular Vesicles

The insulin-responsive glucose transporter, GLUT-4, moves from an intracellular compartment to the cell surface in response to insulin and/or muscle contraction. Treatment of H9c2 myotubes with insulin significantly increased uptake of 2-deoxyglucose. Depolarization of the myotubes by increasing extracellular [K+], which mimics the initial phases of excitation-contraction coupling, also increased 2-deoxyglucose uptake. The K+- but not insulin-evoked increase was blocked by dantrolene, an inhibitor of Ca2+ release from the sarcoplasmic reticulum. In contrast, wortmannin, an inhibitor of phosphatidylinositol 3-kinase, blocked insulin- but not K+-stimulated 2-deoxyglucose uptake. Increased glucose uptake in response to insulin or K+ depolarization was associated with increased GLUT-4 in plasma membranes and depletion of a population of small intracellular GLUT-4-containing vesicles. Similarly, in H9c2 cells transfected with c-myc-tagged GLUT-4, translocation of c-myc GLUT-4 to the cell surface was increased after stimulation with insulin or K+ depolarization. Taken together, these data demonstrate that insulin and K+ depolarization increase glucose uptake by recruiting GLUT-4 from intracellular vesicles to the plasma membrane of H9c2 myotubes via distinct signaling mechanisms.

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