Effects of selective hyperglycemia and hyperinsulinemia on glucose transporters in fetal ovine skeletal muscle

2001 ◽  
Vol 281 (4) ◽  
pp. R1256-R1263 ◽  
Author(s):  
Marianne S. Anderson ◽  
Jing He ◽  
Judy Flowers-Ziegler ◽  
Sherin U. Devaskar ◽  
William W. Hay
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Temporal Correlation ◽  
Utilization Rate ◽  
Fetal Sheep ◽  
Transporter Proteins ◽  
Glut 1 ◽  
Glut 4 ◽  
Glucose Transporter Proteins

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.

Glucose transporter protein responses to selective hyperglycemia or hyperinsulinemia in fetal sheep

2001 ◽  
Vol 281 (5) ◽  
pp. R1545-R1552 ◽  
Author(s):  
Marianne S. Anderson ◽  
Judy Flowers-Ziegler ◽  
Utpala G. Das ◽  
William W. Hay ◽  
Sherin U. Devaskar
Keyword(s):  
Glucose Transporter ◽  
Statistical Significance ◽  
Late Gestation ◽  
The Other ◽  
Utilization Rate ◽  
Fetal Sheep ◽  
Glut 1 ◽  
Transporter Protein ◽  
Glut 4 ◽  
Sustained Increase

The acute effect of selective hyperglycemia or hyperinsulinemia on late gestation fetal ovine glucose transporter protein (GLUT-1, GLUT-3, and GLUT-4) concentrations was examined in insulin-insensitive (brain and liver) and insulin-sensitive (myocardium and fat) tissues at 1, 2.5, and 24 h. Hyperglycemia with euinsulinemia caused a two- to threefold increase in brain GLUT-3, liver GLUT-1, and myocardial GLUT-1 concentrations only at 1 h. There was no change in GLUT-4 protein amounts at any time during the selective hyperglycemia. In contrast, selective hyperinsulinemia with euglycemia led to an immediate and persistent twofold increase in liver GLUT-1, which lasted from 1 until 24 h with a concomitant decline in myocardial tissue GLUT-4 amounts, reaching statistical significance at 24 h. No other significant change in response to hyperinsulinemia was noted in any of the other isoforms in any of the other tissues. Simultaneous assessment of total fetal glucose utilization rate (GURf) during selective hyperglycemia demonstrated a transient 40% increase at 1 and 2.5 h, corresponding temporally with a transient increase in brain GLUT-3 and liver and myocardial GLUT-1 protein amounts. In contrast, selective hyperinsulinemia led to a sustained increase in GURf, corresponding temporally with the persistent increase in hepatic GLUT-1 concentrations. We conclude that excess substrate acutely increases GURf associated with an increase in various tissues of the transporter isoforms GLUT-1 and GLUT-3 that mediate fetal basal glucose transport without an effect on the GLUT-4 isoform that mediates insulin action. This contrasts with the tissue-specific effects of selective hyperinsulinemia with a sustained increase in GURfassociated with a sustained increase in hepatic basal glucose transporter (GLUT-1) amounts and a myocardial-specific emergence of mild insulin resistance associated with a downregulation of GLUT-4.

Time-dependent and tissue-specific effects of circulating glucose on fetal ovine glucose transporters

1999 ◽  
Vol 276 (3) ◽  
pp. R809-R817 ◽  
Author(s):  
Utpala G. Das ◽  
Robert E. Schroeder ◽  
William W. Hay ◽  
Sherin U. Devaskar
Keyword(s):  
Skeletal Muscle ◽  
Gestational Age ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Time Dependent ◽  
Glut 1 ◽  
Glut 4 ◽  
Specific Effects ◽  
Glucose Transporter Proteins ◽  
Maternal Glucose

To determine the cellular adaptations to fetal hyperglycemia and hypoglycemia, we examined the time-dependent effects on basal (GLUT-1 and GLUT-3) and insulin-responsive (GLUT-4) glucose transporter proteins by quantitative Western blot analysis in fetal ovine insulin-insensitive (brain and liver) and insulin-sensitive (myocardium, skeletal muscle, and adipose) tissues. Maternal glucose infusions causing fetal hyperglycemia resulted in a transient 30% increase in brain GLUT-1 but not GLUT-3 levels and a decline in liver and adipose GLUT-1 and myocardial and skeletal muscle GLUT-1 and GLUT-4 levels compared with gestational age-matched controls. Maternal insulin infusions leading to fetal hypoglycemia caused a decline in brain GLUT-3, an increase in brain GLUT-1, and a subsequent decline in liver GLUT-1, with no significant change in insulin-sensitive myocardium, skeletal muscle, and adipose tissue GLUT-1 or GLUT-4 concentrations, compared with gestational age-matched sham controls. We conclude that fetal glucose transporters are subject to a time-dependent and tissue- and isoform-specific differential regulation in response to altered circulating glucose and/or insulin concentrations. These cellular adaptations in GLUT-1 (and GLUT-3) are geared toward protecting the conceptus from perturbations in substrate availability, and the adaptations in GLUT-4 are geared toward development of fetal insulin resistance.

Glucose utilization and glucose transporter proteins GLUT-1 and GLUT-3 in brains of diabetic (db/db) mice

1997 ◽  
Vol 272 (2) ◽  
pp. E267-E274 ◽  
Author(s):  
S. J. Vannucci ◽  
E. M. Gibbs ◽  
I. A. Simpson
Keyword(s):  
Blood Glucose ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Dry Weight ◽  
Mrna Levels ◽  
Brain Growth ◽  
Transporter Proteins ◽  
Glut 1 ◽  
Glucose Transporter Proteins ◽  
And Control

This study describes the effects of diabetes on brain growth, cerebral glucose utilization (CGU), and the glucose transporter proteins GLUT-1 and GLUT-3 in the genetically diabetic db/db mouse. Mice were studied at 5 and 10 wk of age and compared with age-matched nondiabetic littermates. At 5 wk, db/db mice were not yet hyperglycemic, but their body weights were 27.5% greater than those of their nondiabetic littermates. By 10 wk, db/db mice were both hyperglycemic (blood glucose values of 39.3 +/- 4.3 vs. 12.1 +/- 2.1 mmol/l for db/db and control, respectively) and obese, with a twofold increase in body weight. Significant reductions in brain weight were observed at 5 wk (15% decrease in brain wet wt), and no further brain growth was observed, such that by 10 wk, brains of db/db mice were 25% smaller than those of control mice; brain wet weight-to-dry weight ratios were slightly reduced. Global rates of CGU, as determined with 2-[14C]deoxyglucose, were significantly reduced in the 10-wk diabetic mice. Levels of brain glucose and brain-to-blood glucose ratios were increased in 5- and 10-wk db/db mice, reflecting adequate glucose delivery to the brain. Blood-brain barrier GLUT-1 levels were unchanged, and mRNA levels were regionally increased. The expression of the neuronal glucose transporter GLUT-3 was not reduced to a significant extent in brains of db/db mice. The results of this study indicate that the db/db mouse has markedly decelerated brain growth accompanied by global reductions in glucose metabolism that are not due to reductions in glucose transport capacity.

Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle

1990 ◽  
Vol 259 (6) ◽  
pp. E778-E786 ◽  
Author(s):  
T. Ploug ◽  
B. M. Stallknecht ◽  
O. Pedersen ◽  
B. B. Kahn ◽  
T. Ohkuwa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Training Session ◽  
Residual Effect ◽  
Exercise Session ◽  
Transport Capacity ◽  
Glut 1 ◽  
Glut 4 ◽  
Fast Twitch

The effect of 10 wk endurance swim training on 3-O-methylglucose (3-MG) uptake (at 40 mM 3-MG) in skeletal muscle was studied in the perfused rat hindquarter. Training resulted in an increase of approximately 33% for maximum insulin-stimulated 3-MG transport in fast-twitch red fibers and an increase of approximately 33% for contraction-stimulated transport in slow-twitch red fibers compared with nonexercised sedentary muscle. A fully additive effect of insulin and contractions was observed both in trained and untrained muscle. Compared with transport in control rats subjected to an almost exhaustive single exercise session the day before experiment both maximum insulin- and contraction-stimulated transport rates were increased in all muscle types in trained rats. Accordingly, the increased glucose transport capacity in trained muscle was not due to a residual effect of the last training session. Half-times for reversal of contraction-induced glucose transport were similar in trained and untrained muscles. The concentrations of mRNA for GLUT-1 (the erythrocyte-brain-Hep G2 glucose transporter) and GLUT-4 (the adipocyte-muscle glucose transporter) were increased approximately twofold by training in fast-twitch red muscle fibers. In parallel to this, Western blot demonstrated a approximately 47% increase in GLUT-1 protein and a approximately 31% increase in GLUT-4 protein. This indicates that the increases in maximum velocity for 3-MG transport in trained muscle is due to an increased number of glucose transporters.

scholarly journals Hypoglycemic activity of Phaseolus vulgaris (L.) aqueous extract in type 1 diabetic rats

2019 ◽  
Vol 32 (4) ◽  
pp. 210-218
Author(s):  
Tetiana Halenova ◽  
Natalia Raksha ◽  
Olha Kravchenko ◽  
Tetiana Vovk ◽  
Alona Yurchenko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Phaseolus Vulgaris ◽  
Aqueous Extract ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Muscle Cells ◽  
Diabetic Rats ◽  
Hypoglycemic Activity ◽  
Skeletal Muscle Cells ◽  
Glut 4

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.

scholarly journals Effects of Chronic Undernutrition on Glucose Uptake and Glucose Transporter Proteins in Rat Heart

Endocrinology ◽  
2002 ◽  
Vol 143 (11) ◽  
pp. 4295-4303 ◽  
Author(s):  
M. Lucia Gavete ◽  
Maria Agote ◽  
M. Angeles Martin ◽  
Carmen Alvarez ◽  
Fernando Escriva
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Surface Membrane ◽  
Subcellular Fractionation ◽  
High Energy ◽  
Regulatory Subunits ◽  
Glut 1 ◽  
Glut 4 ◽  
Energy Demands ◽  
Glucose Transporter Proteins

Abstract The high energy demands of myocardium are met through the metabolism of lipids and glucose. Importantly, enhanced glucose utilization rates are crucial adaptations of the cardiac cell to some pathological conditions, such as hypertrophy and ischemia, but the effects of undernutrition on heart glucose metabolism are unknown. Our previous studies have shown that undernutrition increases insulin-induced glucose uptake by skeletal muscle. Consequently, we considered the possibility of a similar adaptation in the heart. With this aim, undernourished rats both in the basal state and after euglycemic hyperinsulinemic clamps were used to determine the following parameters in myocardium: glucose uptake, glucose transporter (GLUT) content, and some key components of the insulin signaling cascade. Heart membranes were prepared by subcellular fractionation in sucrose gradients. Although GLUT-4, GLUT-1, and GLUT-3 proteins and GLUT-4/1 mRNAs were reduced by undernutrition, basal and insulin-stimulated 2-deoxyglucose uptake were significantly enhanced. Phosphoinositol 3-kinase activity remained greater than control values in both conditions. The abundance of p85α and p85β regulatory subunits of phosphoinositol 3-kinase was increased as was phospho-Akt during hyperinsulinemia. These changes seem to improve the insulin stimulus of GLUT-1 translocation, as its content was increased at the surface membrane. Such adaptations associated with undernutrition must be crucial to improvement of cardiac glucose uptake.

Glucose transporter proteins GLUT1 and GLUT3 like immunoreactivities in the fetal sheep brain are not reduced by maternal betamethasone treatment

2006 ◽  
Vol 403 (3) ◽  
pp. 261-265 ◽  
Author(s):  
Iwa Antonow-Schlorke ◽  
Martin Ebert ◽  
Thomas Müller ◽  
Harald Schubert ◽  
Andrea Gschanes ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Fetal Sheep ◽  
Transporter Proteins ◽  
Sheep Brain ◽  
Glucose Transporter Proteins

Glucose transporter expression in human skeletal muscle fibers

2000 ◽  
Vol 279 (3) ◽  
pp. E529-E538 ◽  
Author(s):  
M. Gaster ◽  
A. Handberg ◽  
H. Beck-Nielsen ◽  
H. D. Schrøder
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Glucose Transporter ◽  
Muscle Fibers ◽  
Muscle Cells ◽  
Glut 1 ◽  
Adult Muscle ◽  
Glut 4 ◽  
Skeletal Muscle Fibers ◽  
Transporter Expression

The present study was initiated to investigate GLUT-1 through -5 expression in developing and mature human skeletal muscle. To bypass the problems inherent in techniques using tissue homogenates, we applied an immunocytochemical approach, employing the sensitive enhanced tyramide signal amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle fibers, only GLUT-4 was expressed at significant levels. GLUT-1 immunoreactivity was below the detection limit in muscle fibers, indicating that this glucose transporter is of minor importance for muscle glucose supply. Thus we hypothesize that GLUT-4 also mediates basal glucose transport in muscle fibers, possibly through constant exposure to tonal contraction and basal insulin levels.

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 Skeletal muscle glucose transporter protein responses to antenatal glucocorticoids in the ovine fetus

2006 ◽  
Vol 189 (2) ◽  
pp. 219-229 ◽  
Author(s):  
Susan Gray ◽  
Barbara S Stonestreet ◽  
Shanthie Thamotharan ◽  
Grazyna B Sadowska ◽  
Molly Daood ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Biceps Femoris ◽  
Extensor Digitorum ◽  
Corticosteroid Administration ◽  
Biceps Femoris Muscle ◽  
Glut 1 ◽  
Glut 4 ◽  
Ovine Fetus

We investigated the effects of maternal antenatal dexamethasone (Dex) treatment given as a single course (4 doses) or multiple courses (20 doses) on fetal skeletal muscle glucose transporter (GLUT) protein concentrations at 70% of gestation (106 to 107 days with term being 145 to 150 days) in the ovine fetus. Antenatal corticosteroid administration was associated with a decrease in endogenous fetal plasma cortisol concentrations (P < 0.05), fetal hyperglycemia (P < 0.02) and hyperinsulinemia (P < 0.05). These metabolic/hormonal changes were associated with a decrease in fetal body weight (P < 0.05) in the multiple course Dex group compared with the multiple course placebo group. These perturbations were associated with an increase in fetal skeletal muscle GLUT 1 concentrations that mediate basal glucose transport in the extensor digitorum lateralis and extensor digitorum longus muscles (P < 0.05) 18 h after the last dose of Dex was given in the single course group. However, in the multiple course Dex group, a small increase in GLUT 1 was observed only in the biceps femoris. In contrast, both single and multiple courses of antenatal Dex were associated with an increase in the extensor digitorum lateralis and biceps femoris muscle GLUT 4 (insulin-responsive) concentrations (P < 0.05). We conclude that antenatal corticosteroids perturb fetal glucose/insulin homeostasis, which is associated with increases in fetal skeletal muscle glucose transporters to compensate for and attenuate the associated catabolic fetal state. These changes consist of an increase in proteins that mediate basal glucose transport (GLUT 1) to meet immediate energy requirements of the fetal skeletal muscle with an increase in basal insulin sensitivity (GLUT 4) to compensate for the Dex-induced catabolic state after exposure to multiple courses of Dex.

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