In vivo effects of dexamethasone and sucrose on glucose transport (GLUT-4) protein tissue distribution

1996 ◽  
Vol 271 (4) ◽  
pp. E643-E648 ◽  
Author(s):  
L. Coderre ◽  
G. A. Vallega ◽  
P. F. Pilch ◽  
S. R. Chipkin

Tissue-specific changes in GLUT-4 were compared in the following three different rat models by inducing varying degrees of hyperinsulinemia with or without hyperglycemia and hypertriglyceridemia: 1) sucrose feeding (Suc), 2) subcutaneous dexamethasone administration (Dex), and 3) a combination of both treatments (Dex/Suc). Suc raised circulatory insulin and triglyceride levels without affecting plasma glucose, whereas both Dex and Dex/Suc induced significant hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. In adipocytes and skeletal muscle, Suc feeding was not associated with any change in total cellular GLUT-4 levels. However, Suc induced a sevenfold increase in fat cell plasma membrane GLUT-4 levels in the basal state and inhibited GLUT-4 translocation in response to insulin. Administration of Dex or Dex/Suc diminished GLUT-4 expression in fat cells, increased it in skeletal muscle, but did not induce any change in heart. Similar to Suc feeding, Dex and Dex/Suc also increased the amount of GLUT-4 detected at the plasma membrane of adipocytes in the basal state and inhibited GLUT-4 translocation in response to insulin. These results emphasize the specific regulation of GLUT-4 in insulin-sensitive tissues.

1998 ◽  
Vol 274 (4) ◽  
pp. E700-E707 ◽  
Author(s):  
Xiao-Xia Han ◽  
Arend Bonen

We examined the effects of epinephrine (25, 50, and 150 nM) on 1) basal and insulin-stimulated 3- O-methylglucose (3-MG) transport in perfused rat muscles and 2) GLUT-4 in skeletal muscle plasma membranes. Insulin increased glucose transport 330–600% in three types of skeletal muscle [white (WG) and red (RG) gastrocnemius and soleus (SOL)]. Glucose transport was also increased by epinephrine (22–48%) in these muscles ( P < 0.05). In contrast, the insulin-stimulated 3-MG transport was reduced by epinephrine in all three types of muscles; maximal reductions were observed at 25 nM epinephrine in WG (−25%) and RG (−32.5%). A dose-dependent decrease occurred in SOL (−27% at 25 nM; −55% at 150 nM, P < 0.05). Insulin (20 mU/ml) and epinephrine (150 nM) each translocated GLUT-4 to the plasma membrane, and no differences in translocation were observed between insulin and epinephrine ( P > 0.05). In addition, epinephrine did not inhibit insulin-stimulated GLUT-4 translocation, and the combined epinephrine and insulin effects on GLUT-4 translocation were not additive. The increase in surface GLUT-4 was associated with increases in muscle cAMP concentrations, but only when epinephrine alone was present. No relationship was evident between muscle cAMP concentrations and surface GLUT-4 in the combined epinephrine and insulin-stimulated muscles. These studies indicate that epinephrine can translocate GLUT-4 while at the same time increasing glucose transport when insulin is absent, or can inhibit glucose transport when insulin is present.


1976 ◽  
Vol 154 (1) ◽  
pp. 11-21 ◽  
Author(s):  
J P Luzio ◽  
A C Newby ◽  
C N Hales

1. A rapid method for the isolation of hormonally sensitive rat fat-cell plasma membranes was developed by using immunological techniques. 2. Rabbit anti-(rat erythrocyte) sera were raised and shown to cross-react with isolated rat fat-cells. 3. Isolated rat fat-cells were coated with rabbit anti-(rat erythrocyte) antibodies, homogenized and the homogenate made to react with an immunoadsorbent prepared by covalently coupling donkey anti-(rabbit globulin) antibodies to aminocellulose. Uptake of plasma membrane on to the immunoadsorbent was monitored by assaying the enzymes adenylate cyclase and 5′-nucleotidase and an immunological marker consisting of a 125I-labelled anti-(immunoglobulin G)-anti-cell antibody complex bound to the cells before fractionation. Contamination of the plasma-membrane preparation by other subcellular fractions was also investigated. 4. By using this technique, a method was developed allowing 25-40% recovery of plasma membrane from fat-cell homogenates within 30 min of homogenization. 5. Adenylate cyclase in the isolated plasma-membrane preparation was stimulated by 5 μm-adrenaline.


1981 ◽  
Vol 9 (2) ◽  
pp. 232P-232P
Author(s):  
G. J. Belsham ◽  
R. W. Brownsey ◽  
R. M. Denton

1997 ◽  
Vol 273 (4) ◽  
pp. E682-E687 ◽  
Author(s):  
Jared P. Jones ◽  
G. Lynis Dohm

Transport of glucose across the plasma membrane by GLUT-4 and subsequent phosphorylation of glucose by hexokinase II (HKII) constitute the first two steps of glucose utilization in skeletal muscle. This study was undertaken to determine whether epinephrine and/or insulin regulates in vivo GLUT-4 and HKII gene transcription in rat skeletal muscle. In the first experiment, adrenodemedullated male rats were fasted 24 h and killed in the control condition or after being infused for 1.5 h with epinephrine (30 μg/ml at 1.68 ml/h). In the second experiment, male rats were fasted 24 h and killed after being infused for 2.5 h at 1.68 ml/h with saline or glucose (625 mg/ml) or insulin (39.9 μg/ml) plus glucose (625 mg/ml). Nuclei were isolated from pooled quadriceps, tibialis anterior, and gastrocnemius muscles. Transcriptional run-on analysis indicated that epinephrine infusion decreased GLUT-4 and increased HKII transcription compared with fasted controls. Both glucose and insulin plus glucose infusion induced increases in GLUT-4 and HKII transcription of twofold and three- to fourfold, respectively, compared with saline-infused rats. In conclusion, epinephrine and insulin may regulate GLUT-4 and HKII genes at the level of transcription in rat skeletal muscle.


1989 ◽  
Vol 96 (5) ◽  
pp. 1238-1248 ◽  
Author(s):  
Paul L. McNeil ◽  
Susumu Ito

1997 ◽  
Vol 136 (1) ◽  
pp. 137-154 ◽  
Author(s):  
Robert G. Parton ◽  
Michael Way ◽  
Natasha Zorzi ◽  
Espen Stang

Caveolae, flask-shaped invaginations of the plasma membrane, are particularly abundant in muscle cells. We have recently cloned a muscle-specific caveolin, termed caveolin-3, which is expressed in differentiated muscle cells. Specific antibodies to caveolin-3 were generated and used to characterize the distribution of caveolin-3 in adult and differentiating muscle. In fully differentiated skeletal muscle, caveolin-3 was shown to be associated exclusively with sarcolemmal caveolae. Localization of caveolin-3 during differentiation of primary cultured muscle cells and development of mouse skeletal muscle in vivo suggested that caveolin-3 is transiently associated with an internal membrane system. These elements were identified as developing transverse-(T)-tubules by double-labeling with antibodies to the α1 subunit of the dihydropyridine receptor in C2C12 cells. Ultrastructural analysis of the caveolin-3– labeled elements showed an association of caveolin-3 with elaborate networks of interconnected caveolae, which penetrated the depths of the muscle fibers. These elements, which formed regular reticular structures, were shown to be surface-connected by labeling with cholera toxin conjugates. The results suggest that caveolin-3 transiently associates with T-tubules during development and may be involved in the early development of the T-tubule system in muscle.


1994 ◽  
Vol 77 (4) ◽  
pp. 1597-1601 ◽  
Author(s):  
J. Gao ◽  
J. Ren ◽  
E. A. Gulve ◽  
J. O. Holloszy

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.


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