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.

scholarly journals Differential Expression of Glucose Transporter Proteins GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in the Placenta of Macrosomic, Small-for-Gestational-Age and Growth-Restricted Foetuses

2021 ◽  
Vol 10 (24) ◽  
pp. 5833
Author(s):  
Paweł Jan Stanirowski ◽  
Dariusz Szukiewicz ◽  
Agata Majewska ◽  
Mateusz Wątroba ◽  
Michał Pyzlak ◽  
...  
Keyword(s):  
Gestational Age ◽  
Small For Gestational Age ◽  
Glucose Transporter ◽  
Placental Tissue ◽  
Glucose Transporters ◽  
Computer Assisted ◽  
Vascular Density ◽  
Transporter Proteins ◽  
Glut 1 ◽  
Glucose Transporter Proteins

Placental transfer of glucose constitutes one of the major determinants of the intrauterine foetal growth. The objective of the present study was to evaluate the expression of glucose transporter proteins GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in the placenta of macrosomic, small-for-gestational-age (SGA) and growth-restricted foetuses (FGR). A total of 70 placental tissue samples were collected from women who delivered macrosomic ≥4000 g (n = 26), SGA (n = 11), growth-restricted (n = 13) and healthy control neonates (n = 20). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected GLUT proteins. Immunohistochemical staining identified the presence of all glucose transporters in the placental tissue. Quantitative morphometric analysis performed for the vascular density-matched placental samples revealed a significant decrease in GLUT-1 and increase in GLUT-3 protein expression in pregnancies complicated by FGR as compared to other groups (p < 0.05). In addition, expression of GLUT-8 was significantly decreased among SGA foetuses (p < 0.05). No significant differences in GLUTs expression were observed in women delivering macrosomic neonates. In the SGA group foetal birth weight (FBW) was negatively correlated with GLUT-3 (rho = −0.59, p < 0.05) and positively with GLUT-12 (rho = 0.616, p < 0.05) placental expression. In addition, a positive correlation between FBW and GLUT-12 expression in the control group (rho = 0.536, p < 0.05) was noted. In placentas derived from FGR-complicated pregnancies the expression of two major glucose transporters GLUT-1 and GLUT-3 is altered. On the contrary, idiopathic foetal macrosomia is not associated with changes in the placental expression of GLUT-1, GLUT-3, GLUT-8 and GLUT-12 proteins.

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.

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 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.

Insulin induces translocation of GLUT-4 glucose transporters in human skeletal muscle

1995 ◽  
Vol 268 (4) ◽  
pp. E613-E622 ◽  
Author(s):  
A. Guma ◽  
J. R. Zierath ◽  
H. Wallberg-Henriksson ◽  
A. Klip
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Human Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Vastus Lateralis ◽  
Glucose Transporters ◽  
Membrane Markers ◽  
Glut 4 ◽  
Muscle Biopsies

Understanding the molecular mechanisms involved in the regulation of glucose transport into human muscle is necessary to unravel possible defects in glucose uptake associated with insulin resistance in humans. Here we report a strategy to subfractionate human skeletal muscle biopsies (0.5 g) removed from vastus lateralis during a euglycemic insulinemic clamp procedure. A sucrose gradient separated total membranes into five fractions. Fraction 25 (25% sucrose) contained the plasma membrane markers alpha 1- and alpha 2-subunits of the Na(+)-K(+)-adenosinetriphosphatase and the GLUT-5 hexose transporter, recently immunolocalized to the cell surface of human skeletal muscle. The dihydropyridine receptor, a transverse tubule marker, was present exclusively in this fraction. The GLUT-4 glucose transporter was more concentrated in fraction 27.5 (27.5% sucrose) and largely diminished in plasma membrane markers. Open skeletal muscle biopsies were removed before and 30 min after clamping insulin to 550 pM. This increased GLUT-4 protein by 1.61-fold in fraction 25 and lowered it by 50% in fraction 27.5. Thus physiological concentrations of insulin induce translocation of glucose transporters from an internal membrane pool to surface membranes in human skeletal muscle.

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.

Effect of physical training on glucose transporter protein and mRNA levels in rat adipocytes

1993 ◽  
Vol 265 (1) ◽  
pp. E128-E134 ◽  
Author(s):  
B. Stallknecht ◽  
P. H. Andersen ◽  
J. Vinten ◽  
L. L. Bendtsen ◽  
J. Sibbersen ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Physical Training ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Intrinsic Activity ◽  
Mrna Levels ◽  
Glut 1 ◽  
Transporter Protein ◽  
Glut 4 ◽  
Adipocyte Volume

Physical training increases insulin-stimulated glucose transport and the number of glucose transporters in adipocytes measured by cytochalasin B binding. In the present study we used immunoblotting to measure the abundance of two glucose transporters (GLUT-4, GLUT-1) in white adipocytes from trained rats. Furthermore, the abundance of the mRNAs for these proteins and glucose transport was measured. Rats were swim-trained for 10 wk, and adipocytes were isolated from epididymal fat pads. The amount of GLUT-4/adipocyte volume unit was significantly higher in trained animals compared with both age- and cell size-matched animals. The amount of GLUT-4 mRNA was also increased by training and it decreased with increasing age. Furthermore, young age as well as training was accompanied by relatively low GLUT-4 protein/mRNA and relatively high overall GLUT-4 efficiency (recruitability and/or intrinsic activity). GLUT-1 protein and mRNA levels/adipocyte volume did not change with age or training.

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.

scholarly journals Diabetes and obesity during pregnancy alter insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue

2009 ◽  
Vol 44 (4) ◽  
pp. 213-223 ◽  
Author(s):  
Michelle Colomiere ◽  
Michael Permezel ◽  
Martha Lappas
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Transporter ◽  
Insulin Signalling ◽  
Signalling Pathway ◽  
Glut 1 ◽  
Glut 4 ◽  
Insulin Signalling Pathway ◽  
Subcutaneous Adipose ◽  
Diabetes And Obesity

Severe insulin resistance is a defining attribute of gestational diabetes mellitus (GDM). It is postulated that alterations in the insulin-signalling pathway and subsequent glucose disposal are the underlying cause of insulin resistance in patients with GDM. The purpose of this study was to profile the insulin-signalling pathway and intermediates in insulin-sensitive tissues. Subcutaneous adipose tissue and skeletal muscle were collected from normal glucose-tolerant (NGT) and insulin-controlled GDM in both non-obese and obese cohorts (n=6–8 per subgroup). Expression studies of the insulin-signalling pathway were performed using western blotting and quantitative reverse transcription-PCR. This study demonstrated altered mRNA expression of insulin receptor substrate (IRS)-1, IRS-2, glucose transporter (GLUT)-1, GLUT-4 and glycogen synthase kinase (GSK)-3 isoforms genes in adipose tissue in GDM women in comparison to NGT pregnant controls. In skeletal muscle, insulin-controlled GDM was associated with decreased IRS-1, phosphatidylinositol-3-kinase (PI3-K) p85α, GLUT-1 and -4, GSK-3 isoforms and phosphoinositide-dependent kinase-1. Both adipose tissue and skeletal muscle from women with GDM displayed decreased IRS-1 and GLUT-4 and increased PI3-K p85α protein expression. Both skeletal muscle and adipose tissue from obese women demonstrated lower GLUT-1 and -4 mRNA expression and diminished GLUT-4 protein expression in skeletal muscle only. Collectively, our results suggest that diabetes and obesity during pregnancy cause defects in insulin-signalling transduction in adipose tissue and skeletal muscle and may be the underlying cause of GDM.

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