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.

Short-term exercise enhances insulin-stimulated GLUT-4 translocation and glucose transport in adipose cells

1998 ◽  
Vol 85 (6) ◽  
pp. 2106-2111 ◽  
Author(s):  
Cynthia M. Ferrara ◽  
Thomas H. Reynolds ◽  
Mary Jane Zarnowski ◽  
Joseph T. Brozinick ◽  
Samuel W. Cushman
Keyword(s):  
Exercise Training ◽  
Cell Surface ◽  
Glucose Transport ◽  
Transport Activity ◽  
Short Term ◽  
Adipose Cell ◽  
Glut 4 ◽  
Glut 4 Translocation ◽  
Adipose Cell Size ◽  
Adipose Cells

This investigation examined the effects of short-term exercise training on insulin-stimulated GLUT-4 glucose transporter translocation and glucose transport activity in rat adipose cells. Male Wistar rats were randomly assigned to a sedentary (Sed) or swim training group (Sw, 4 days; final 3 days: 2 × 3 h/day). Adipose cell size decreased significantly but minimally (∼20%), whereas total GLUT-4 increased by 30% in Sw vs. Sed rats. Basal 3- O-methyl-d-[14C]glucose transport was reduced by 62%, whereas maximally insulin-stimulated (MIS) glucose transport was increased by 36% in Sw vs. Sed rats. MIS cell surface GLUT-4 photolabeling was 44% higher in the Sw vs. Sed animals, similar to the increases observed in MIS glucose transport activity and total GLUT-4. These results suggest that increases in total GLUT-4 and GLUT-4 translocation to the cell surface contribute to the increase in MIS glucose transport with short-term exercise training. In addition, the results suggest that the exercise training-induced adaptations in glucose transport occur more rapidly than previously thought and with minimal changes in adipose cell size.

Additive effect of contractions and insulin on GLUT-4 translocation into the sarcolemma

1994 ◽  
Vol 77 (4) ◽  
pp. 1597-1601 ◽  
Author(s):  
J. Gao ◽  
J. Ren ◽  
E. A. Gulve ◽  
J. O. Holloszy
Keyword(s):  
Plasma Membrane ◽  
Glucose Transport ◽  
Membrane Fraction ◽  
Glucose Transporter ◽  
Subcellular Fractionation ◽  
Muscle Group ◽  
Intracellular Membrane ◽  
Glut 4 ◽  
Incremental Effect ◽  
Glut 4 Translocation

The maximal effects of insulin and muscle contractions on glucose transport are additive. GLUT-4 is the major glucose transporter isoform expressed in skeletal muscle. Muscle contraction and insulin each induce translocation of GLUT-4 from intracellular sites into the plasma membrane. The purpose of this study was to test the hypothesis that the incremental effect of contractions and insulin on glucose transport is mediated by additivity of the maximal effects of these stimuli on GLUT-4 translocation into the sarcolemma. Anesthetized rats were given insulin by intravenous infusion to raise plasma insulin to 2,635 +/- 638 microU/ml. The gastrocnemius-plantaris-soleus group was stimulated to contract via the sciatic nerve by using a protocol that maximally activates glucose transport. After treatment with insulin, contractions, or insulin plus contractions or no treatment, the gastrocnemius-plantaris-soleus muscle group was dissected out and was subjected to subcellular fractionation to separate the plasma membrane and intracellular membrane fractions. Insulin induced a 70% increase and contractions induced a 113% increase in the GLUT-4 content of the plasma membrane fraction. The effects of insulin and contractions were additive, as evidenced by a 185% increase in the GLUT-4 content of the sarcolemmal fraction. This finding provides evidence that the incremental effect of maximally effective insulin and contractile stimuli on glucose transport is mediated by additivity of their effects on GLUT-4 translocation into the sarcolemma.

Effect of diet on insulin- and contraction-mediated glucose transport and uptake in rat muscle

1995 ◽  
Vol 269 (3) ◽  
pp. R544-R551 ◽  
Author(s):  
X. Han ◽  
T. Ploug ◽  
H. Galbo
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Fiber Types ◽  
Transport Capacity ◽  
Glut 1 ◽  
Glut 4 ◽  
Red Muscle ◽  
Muscle Glucose Transport ◽  
Stimulation Of

A diet rich in fat diminishes insulin-mediated glucose uptake in muscle. This study explored whether contraction-mediated glucose uptake is also affected. Rats were fed a diet rich in fat (FAT, 73% of energy) or carbohydrate (CHO, 66%) for 5 wk. Hindquarters were perfused, and either glucose uptake or glucose transport capacity (uptake of 3-O-[14C]-methyl-D-glucose (40 mM)) was measured. Amounts of glucose transporter isoform GLUT-1 and GLUT-4 glucose-transporting proteins were determined by Western blot. Glucose uptake was lower (P < 0.05) in hindlegs from FAT than from CHO rats at submaximum and maximum insulin [4 +/- 0.4 vs. 5 +/- 0.3 (SE) mumol.min-1.leg-1 at 150 microU/ml insulin] as well as during prolonged stimulation of the sciatic nerve (4.4 +/- 0.4 vs. 5.6 +/- 0.6 mumol.min-1.leg-1). Maximum glucose transport elicited by insulin (soleus: 1.7 +/- 0.2 vs. 2.6 +/- 0.2 mumol.g-1.5 min-1, P < 0.05) or contractions (soleus: 1.8 +/- 0.2 vs. 2.6 +/- 0.3, P < 0.05) in red muscle was decreased in parallel in FAT compared with CHO rats. GLUT-4 content was decreased by 13-29% (P < 0.05) in the various fiber types, whereas GLUT-1 content was identical in FAT compared with CHO rats. It is concluded that a FAT diet reduces both insulin and contraction stimulation of glucose uptake in muscle and that these effects are associated with diminished skeletal muscle glucose transport capacities and GLUT-4 contents.

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.

scholarly journals The efficient intracellular sequestration of the insulin-regulatable glucose transporter (GLUT-4) is conferred by the NH2 terminus

1992 ◽  
Vol 117 (4) ◽  
pp. 729-743 ◽  
Author(s):  
RC Piper ◽  
C Tai ◽  
JW Slot ◽  
CS Hahn ◽  
CM Rice ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Glucose Transport ◽  
Cho Cells ◽  
Sindbis Virus ◽  
Glucose Transporter ◽  
Intracellular Compartment ◽  
Glut 1 ◽  
Glut 4 ◽  
Intracellular Sequestration

GLUT-4 is the major facilitative glucose transporter isoform in tissues that exhibit insulin-stimulated glucose transport. Insulin regulates glucose transport by the rapid translocation of GLUT-4 from an intracellular compartment to the plasma membrane. A critical feature of this process is the efficient exclusion of GLUT-4 from the plasma membrane in the absence of insulin. To identify the amino acid domains of GLUT-4 which confer intracellular sequestration, we analyzed the subcellular distribution of chimeric glucose transporters comprised of GLUT-4 and a homologous isoform, GLUT-1, which is found predominantly at the cell surface. These chimeric transporters were transiently expressed in CHO cells using a double subgenomic recombinant Sindbis virus vector. We have found that wild-type GLUT-4 is targeted to an intracellular compartment in CHO cells which is morphologically similar to that observed in adipocytes and muscle cells. Sindbis virus-produced GLUT-1 was predominantly expressed at the cell surface. Substitution of the GLUT-4 amino-terminal region with that of GLUT-1 abolished the efficient intracellular sequestration of GLUT-4. Conversely, substitution of the NH2 terminus of GLUT-1 with that of GLUT-4 resulted in marked intracellular sequestration of GLUT-1. These data indicate that the NH2-terminus of GLUT-4 is both necessary and sufficient for intracellular sequestration.

Glycogen supercompensation masks the effect of a traininginduced increase in GLUT-4 on muscle glucose transport

1998 ◽  
Vol 85 (1) ◽  
pp. 133-138 ◽  
Author(s):  
Helen H. Host ◽  
Polly A. Hansen ◽  
Lorraine A. Nolte ◽  
May M. Chen ◽  
John O. Holloszy
Keyword(s):  
Exercise Training ◽  
Glucose Transport ◽  
Muscle Glycogen ◽  
Glucose Transporter ◽  
Exercise Bout ◽  
Twofold Increase ◽  
Control Value ◽  
Glut 4 ◽  
Carbohydrate Feeding ◽  
Muscle Glucose Transport

Endurance exercise training induces a rapid increase in the GLUT-4 isoform of the glucose transporter in muscle. In fasted rats, insulin-stimulated muscle glucose transport is increased in proportion to the increase in GLUT-4. There is evidence that high muscle glycogen may decrease insulin-stimulated glucose transport. This study was undertaken to determine whether glycogen supercompensation interferes with the increase in glucose transport associated with an exercise-induced increase in GLUT-4. Rats were trained by means of swimming for 6 h/day for 2 days. Rats fasted overnight after the last exercise bout had an approximately twofold increase in epitrochlearis muscle GLUT-4 and an associated approximately twofold increase in maximally insulin-stimulated glucose transport activity. Epitrochlearis muscles of rats fed rodent chow after exercise were glycogen supercompensated (86.4 ± 4.8 μmol/g wet wt) and showed no significant increase in maximally insulin-stimulated glucose transport above the sedentary control value despite an approximately twofold increase in GLUT-4. Fasting resulted in higher basal muscle glucose transport rates in both sedentary and trained rats but did not significantly increase maximally insulin-stimulated transport in the sedentary group. We conclude that carbohydrate feeding that results in muscle glycogen supercompensation prevents the increase in maximally insulin-stimulated glucose transport associated with an exercise training-induced increase in muscle GLUT-4.

Decreased insulin-stimulated GLUT-4 translocation in glycogen-supercompensated muscles of exercised rats

1999 ◽  
Vol 276 (5) ◽  
pp. E907-E912 ◽  
Author(s):  
Kentaro Kawanaka ◽  
Dong-Ho Han ◽  
Lorraine A. Nolte ◽  
Polly A. Hansen ◽  
Akira Nakatani ◽  
...  
Keyword(s):  
Cell Surface ◽  
Glucose Transport ◽  
Biosynthetic Pathway ◽  
Glycogen Content ◽  
Hexosamine Biosynthetic Pathway ◽  
Glut 4 ◽  
Glut 4 Translocation ◽  
Insulin Responsiveness ◽  
Exercise Induced

It was recently found that the effect of an exercise-induced increase in muscle GLUT-4 on insulin-stimulated glucose transport is masked by a decreased responsiveness to insulin in glycogen-supercompensated muscle. We evaluated the role of hexosamines in this decrease in insulin responsiveness and found that UDP- N-acetyl hexosamine concentrations were not higher in glycogen-supercompensated muscles than in control muscles with a low glycogen content. We determined whether the smaller increase in glucose transport is due to translocation of fewer GLUT-4 to the cell surface with the 2- N-4-(1-azi-2,2,2-trifluroethyl)-benzoyl-1,3-bis(d-mannose-4-yloxy)-2-propylamine (ATB-[2-3H]BMPA) photolabeling technique. The insulin-induced increase in GLUT-4 at the cell surface was no greater in glycogen-supercompensated exercised muscle than in muscles of sedentary controls and only 50% as great as in exercised muscles with a low glycogen content. We conclude that the decreased insulin responsiveness of glucose transport in glycogen-supercompensated muscle is not due to increased accumulation of hexosamine biosynthetic pathway end products and that the smaller increase in glucose transport is mediated by translocation of fewer GLUT-4 to the cell surface.

GLUT-4myc ectopic expression in L6 myoblasts generates a GLUT-4-specific pool conferring insulin sensitivity

1999 ◽  
Vol 277 (3) ◽  
pp. E572-E578 ◽  
Author(s):  
Atsunori Ueyama ◽  
Karen L. Yaworsky ◽  
Qinghua Wang ◽  
Yousuke Ebina ◽  
Amira Klip
Keyword(s):  
Insulin Sensitivity ◽  
Cell Surface ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Ectopic Expression ◽  
Fat Cells ◽  
Intracellular Fraction ◽  
Glut 4 ◽  
Intracellular Compartments ◽  
Stimulation Of

Insulin stimulates glucose uptake into muscle and fat cells via recruitment of the glucose transporter 4 (GLUT-4) from intracellular store(s) to the cell surface. Robust stimulation of glucose uptake by insulin coincides with the expression of GLUT-4 during differentiation of muscle and fat cells, but it is not known if GLUT-4 expression suffices to confer insulin sensitivity to glucose uptake. We have therefore examined the effect of expression of a myc epitope-tagged GLUT-4 (GLUT-4myc) into L6 myoblasts, which do not express endogenous GLUT-4 until differentiated into myotubes. Ectopic expression of GLUT-4myc markedly improved insulin sensitivity of glucose uptake in L6 myoblasts. The GLUT-4myc protein distributed equally to the cell surface and intracellular compartments in myoblasts, and the intracellular fraction of GLUT-4myc further increased in myotubes. In myoblasts, the intracellular GLUT-4myc compartment contained the majority of the insulin-regulatable amino peptidase (IRAP) but less than half of the GLUT-1, suggesting segregation of GLUT-4myc and IRAP to a specific cellular locus. Insulin stimulation of phosphatidylinositol 3-kinase and protein kinase B-α activities was similar for L6-GLUT-4myc myoblasts and myotubes. At both stages, GLUT-4myc responded to insulin by translocating to the cell surface. These results suggest that GLUT-4myc segregates into a specific compartment in L6 myoblasts and confers insulin sensitivity to these cells. L6-GLUT-4myc myoblasts, which are easily transfectable with various constructs, are a useful resource to study insulin action.

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.

Sign in / Sign up

Export Citation Format

Share Document