Skeletal muscle glucose transporter (GLUT-4) protein is decreased in lactating goats

1997 ◽  
Vol 65 (2) ◽  
pp. 257-265 ◽  
Author(s):  
M. Balage ◽  
J. F. Hocquette ◽  
B. Graulet ◽  
P. Ferre ◽  
J. Grizard

AbstractLactation in goats is associated with an insulin resistance manifested by an impairment of the ability of insulin maximally to stimulate skeletal muscle glucose utilization. The mechanism responsible for this modification is unknown. Therefore an investigation was made of the insulin-sensitive glucose transporter (GLUT-4) in three skeletal muscles from six lactating (peak of lactation) and six non-lactating goats. GLUT-4 protein content was assessed in crude membrane preparations and Triton X-100 extracts by Western-blot analysis. Lactation resulted in a decrease in GLUT-4 protein content. This decrease was more pronounced in oxidoglycolytic muscles (proportionately -0·40 to -0·60 in m. tensor fasciae latae and longissimus dorsi) than in oxidative muscles (-0·20 in masseter). Down-regulation of the insulin-sensitive glucose transporter (GLUT-4) expression in skeletal muscles from lactating goats may be responsible for the decrease in insulin responsiveness of glucose utilization previously observed in vivo.

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.


2019 ◽  
Vol 32 (4) ◽  
pp. 210-218
Author(s):  
Tetiana Halenova ◽  
Natalia Raksha ◽  
Olha Kravchenko ◽  
Tetiana Vovk ◽  
Alona Yurchenko ◽  
...  

Abstract The aim of the present study was to evaluate the hypoglycemic activity of the aqueous extract from the fruit walls of Phaseolus vulgaris pods and to examine the potential mechanism underlying the improvement of the glycemic level. In the course of the study, diabetes mellitus was induced in rats with a single intraperitoneal injection of streptozotocin (45 mg·kg−1 b.w.). Diabetic and control rats were then orally administered with a single-dose or repeated-dose (28 day) of P. vulgaris extract (200 mg·kg−1). Results show that the extract was found to possess significant hypoglycemic activity, and the study of glucose utilization by isolated rat hemidiaphragm suggests that the aqueous extract may enhance the peripheral utilization of glucose. The subsequent experiments have revealed that the P. vulgaris extract could increase glucose transporter 4 (GLUT-4) content in skeletal muscle cells of control and diabetic rats. Our data also indicate that the P. vulgaris extract did not affect the content of the insulin receptor, but significantly reduced the total tyrosine kinase activity in skeletal muscle cells of both experimental groups of rats. The present results clearly indicated that P. vulgaris extract may be beneficial for reducing hyperglycemia through its potency in regulation of glucose utilization via GLUT-4, but the current mechanism remains to be unidentified.


1997 ◽  
Vol 83 (6) ◽  
pp. 2043-2047 ◽  
Author(s):  
Kentaro Kawanaka ◽  
Izumi Tabata ◽  
Shigeru Katsuta ◽  
Mitsuru Higuchi

Kawanaka, Kentaro, Izumi Tabata, Shigeru Katsuta, and Mitsuru Higuchi. Changes in insulin-stimulated glucose transport and GLUT-4 protein in rat skeletal muscle after training. J. Appl. Physiol. 83(6): 2043–2047, 1997.—After running training, which increased GLUT-4 protein content in rat skeletal muscle by <40% compared with control rats, the training effect on insulin-stimulated maximal glucose transport (insulin responsiveness) in skeletal muscle was short lived (24 h). A recent study reported that GLUT-4 protein content in rat epitrochlearis muscle increased dramatically (∼2-fold) after swimming training (J.-M. Ren, C. F. Semenkovich, E. A. Gulve, J. Gao, and J. O. Holloszy. J. Biol. Chem. 269, 14396–14401, 1994). Because GLUT-4 protein content is known to be closely related to skeletal muscle insulin responsiveness, we thought it possible that the training effect on insulin responsiveness may remain for >24 h after swimming training if GLUT-4 protein content decreases gradually from the relatively high level and still remains higher than control level for >24 h after swimming training. Therefore, we examined this possibility. Male Sprague-Dawley rats swam 2 h a day for 5 days with a weight equal to 2% of body mass. Approximately 18, 42, and 90 h after cessation of training, GLUT-4 protein concentration and 2-[1,2-3H]deoxy-d-glucose transport in the presence of a maximally stimulating concentration of insulin (2 mU/ml) were examined by using incubated epitrochlearis muscle preparation. Swimming training increased GLUT-4 protein concentration and insulin responsiveness by 87 and 85%, respectively, relative to age-matched controls when examined 18 h after training. Forty-two hours after training, GLUT-4 protein concentration and insulin responsiveness were still higher by 52 and 51%, respectively, in muscle from trained rats compared with control. GLUT-4 protein concentration and insulin responsiveness in trained muscle returned to sedentary control level within 90 h after training. We conclude that 1) the change in insulin responsiveness during detraining is directly related to muscle GLUT-4 protein content, and 2) consequently, the greater the increase in GLUT-4 protein content that is induced by training, the longer an effect on insulin responsiveness persists after the training.


1990 ◽  
Vol 271 (2) ◽  
pp. 421-425 ◽  
Author(s):  
M C Sugden ◽  
Y L Liu ◽  
M J Holness

In the fed state, hyperthyroidism increased glucose utilization indices (GUIs) of skeletal muscles containing a lower proportion of oxidative fibres. Glycogen concentrations were unchanged, but active pyruvate dehydrogenase (PDHa) activities were decreased. Hyperthyroidism attenuated the effects of 48 h of starvation to decrease muscle GUI. Glycogen concentrations and PDHa activities after 48 h of starvation were low and similar in euthyroid and hyperthyroid rats. The increase in glucose uptake and phosphorylation relative to oxidation and storage in skeletal muscle induced by hyperthyroidism may contribute to increased glucose re-cycling in the fed hyperthyroid state and to glucose turnover in the starved hyperthyroid state.


1998 ◽  
Vol 275 (2) ◽  
pp. E187-E196 ◽  
Author(s):  
Min Zhou ◽  
Lidia Sevilla ◽  
Gino Vallega ◽  
Peng Chen ◽  
Manuel Palacin ◽  
...  

We have established a simple procedure for the separation of intracellular pool(s) of glucose transporter isoform GLUT-4-containing vesicles from the surface sarcolemma and T tubule membranes of rat skeletal myocytes. This procedure enabled us to immunopurify intracellular GLUT-4-containing vesicles and to demonstrate that 20–30% of the receptors for insulin-like growth factor II/mannose 6-phosphate and transferrin are colocalized with GLUT-4 in the same vesicles. Using our new fractionation procedure as well as cell surface biotinylation, we have shown that these receptors are translocated from their intracellular compartment(s) to the cell surface along with GLUT-4 after insulin stimulation in vivo. Denervation causes a considerable downregulation of GLUT-4 protein in skeletal muscle but does not affect the level of expression of other known component proteins of the corresponding vesicles. Moreover, the sedimentation coefficient of these vesicles remains unchanged by denervation. We suggest that the normal level of GLUT-4 expression is not necessary for the structural organization and insulin-sensitive translocation of its cognate intracellular compartment.


1995 ◽  
Vol 79 (6) ◽  
pp. 1936-1938 ◽  
Author(s):  
J. A. Houmard ◽  
M. S. Hickey ◽  
G. L. Tyndall ◽  
K. E. Gavigan ◽  
G. L. Dohm

Insulin-responsive glucose transporter (GLUT-4) content increases by 1.8-fold in skeletal muscle with 14 wk of exercise training [Houmard et al. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E896-E901, 1993]. The purpose of this study was to determine whether more short-term training (7 days) increases GLUT-4 protein content in human skeletal muscle. Seven sedentary men [25.0 +/- 1.1 (SE) yr, 44.1 +/- 2.2 ml.kg-1.min-1 maximal O2 uptake, 14.9 +/- 2.1% body fat] were examined before and after 7 days of cycle ergometer training (1 h/day, 76 +/- 2% maximal heart rate). Needle biopsy samples from the vastus lateralis were used to determine GLUT-4 protein content. Muscle GLUT-4 increased (P < 0.05) by an average of 2.8 +/- 0.5-fold with 7 days of training. GLUT-4 content in skeletal muscle thus increases substantially with short-term exercise training.


2001 ◽  
Vol 281 (4) ◽  
pp. R1256-R1263 ◽  
Author(s):  
Marianne S. Anderson ◽  
Jing He ◽  
Judy Flowers-Ziegler ◽  
Sherin U. Devaskar ◽  
William W. Hay

We measured net fetal glucose uptake rate from the placenta, shown previously to be equal to total fetal glucose utilization rate (GURf) and proportional to fetal hindlimb skeletal muscle glucose utilization, under normal conditions and after 1, 2.5, and 24 h of selective hyperglycemia (↑G) or selective hyperinsulinemia (↑I). We simultaneously measured the amount of Glut 1 and Glut 4 glucose transporter proteins in fetal sheep skeletal muscle. With ↑G, GURf was increased ∼40% at 1 and 2.5 h but returned to the control rate by 24 h. This transient ↑G-specific ↑GURf was associated with increased plasma membrane-associated Glut 1 (4-fold) and intracellular Glut 4 (3-fold) protein beginning at 1 h. With ↑I, GURf was increased ∼70% at 1, 2.5, and 24 h. This more sustained ↑I-specific ↑GURf was associated with a significant increase in Glut 4 protein (2-fold) at 2.5 h but no change in Glut 1 protein. These results show that ↑G and ↑I have independent effects on the amount of Glut 1 and Glut 4 glucose transporter proteins in ovine fetal skeletal muscle. These effects are time dependent and isoform specific and may contribute to increased glucose utilization in fetal skeletal muscle. The lack of a sustained temporal correlation between the increase in transporter proteins and glucose utilization rates indicates that subcellular localization and activity of a transporter or tissues other than the skeletal muscle contribute to net GURf.


1997 ◽  
Vol 272 (5) ◽  
pp. C1734-C1738 ◽  
Author(s):  
S. Kristiansen ◽  
J. Jones ◽  
A. Handberg ◽  
G. L. Dohm ◽  
E. A. Richter

We have recently shown that eccentric contractions (ECs; forced lengthening of active muscle) elicit a delayed decrease in glucose transporter (GLUT-4) protein content in rat skeletal muscle and a decrease in subsequent contraction-stimulated glucose transport. Here, we investigate whether this decrease in total GLUT-4 protein after prior ECs is due to changes in GLUT-4 gene transcription rate and GLUT-4 mRNA level. Furthermore, the effect of prior ECs on sarcolemmal GLUT-4 protein content in plasma membrane (PM) vesicles isolated from contraction-stimulated muscle was determined. Rat gastrocnemius muscle was electrically stimulated for ECs, and the contralateral muscle served, as unstimulated control (UC). Two days later, the total GLUT-4 protein content was decreased by 50% (P < 0.05) and 32% (P < 0.05) in the white and red gastrocnemius muscle, respectively. Furthermore, the GLUT-4 mRNA concentration was decreased by 41% (P < 0.05) in both the white and red gastrocnemius muscle. Moreover, the GLUT-4 transcription rate, determined by nuclear run-on analysis, was decreased by 75% (P < 0.05) in mixed EC gastrocnemius muscle compared with UC muscle. PM vesicles were isolated from EC and UC muscle after 15 min of isometric contractions. The PM GLUT-4 protein content was reduced by 51% (P < 0.05) in EC muscle compared with UC muscle. In conclusion, 2 days after ECs, the GLUT-4 transcription rate, GLUT-4 mRNA, and GLUT-4 protein content were decreased in rat skeletal muscle. Moreover, the PM GLUT-4 protein content in contraction-stimulated muscle was decreased. We suggest that eccentric muscle contractions decrease muscle GLUT-4 transcription rate, resulting in a lower GLUT-4 protein content, which in turn decreases the number of GLUT-4 transporters translocated to the sarcolemma, ultimately leading to decreased contraction-induced muscle glucose transport.


2002 ◽  
Vol 282 (2) ◽  
pp. R464-R474 ◽  
Author(s):  
Sophie Lemosquet ◽  
Elisabeth Debras ◽  
Michèle Balage ◽  
Jean François Hocquette ◽  
Henri Rulquin ◽  
...  

This work was designed to study the effect of a 3-day mild hyperglycemia (5.3 vs. 3.3 mM) on the regulation of glucose metabolism in lactating goats. Glucose was intravenously infused at variable rates simultaneously with a constant potassium-amino acid infusion. Diet plus substrate infusion maintained net energy but not protein supply. Milk yield did not change. Skeletal muscle glucose transporter (GLUT-4) was analyzed before and after hyperglycemia. In addition, the acute effect of medium and high insulin doses on glucose turnover was measured in vivo during euglycemic and hyperglycemic hyperinsulinemic clamps under potassium and amino acid replacement. Hyperglycemia reduced the endogenous glucose appearance but increased glucose disposal. It decreased the total membrane-associated GLUT-4 protein in skeletal muscle. In contrast, it improved the acute insulin-stimulated glucose disposal. Both the level and duration (3 days) of hyperglycemia contributed to this improvement. We conclude that short-term mild hyperglycemia has similar effects in lactating goats as those already observed in nonlactating rodents or humans.


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