scholarly journals Glucocorticoids Enhance Intestinal Glucose Uptake Via the Dimerized Glucocorticoid Receptor in Enterocytes

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1783-1794 ◽  
Author(s):  
Sybille D. Reichardt ◽  
Michael Föller ◽  
Rexhep Rexhepaj ◽  
Ganesh Pathare ◽  
Kerstin Minnich ◽  
...  
Keyword(s):  
Small Intestine ◽  
Glucose Uptake ◽  
Molecular Mechanism ◽  
Glucose Transport ◽  
Transcriptional Control ◽  
Glucose Transporter ◽  
Gene Activation ◽  
Mouse Strains ◽  
Glucose Transporter 1

Glucocorticoid (GC) treatment of inflammatory disorders, such as inflammatory bowel disease, causes deranged metabolism, in part by enhanced intestinal resorption of glucose. However, the underlying molecular mechanism is poorly understood. Hence, we investigated transcriptional control of genes reported to be involved in glucose uptake in the small intestine after GC treatment and determined effects of GC on electrogenic glucose transport from transepithelial currents. GRvillinCre mice lacking the GC receptor (GR) in enterocytes served to identify the target cell of GC treatment and the requirement of the GR itself; GRdim mice impaired in dimerization and DNA binding of the GR were used to determine the underlying molecular mechanism. Our findings revealed that oral administration of dexamethasone to wild-type mice for 3 d increased mRNA expression of serum- and GC-inducible kinase 1, sodium-coupled glucose transporter 1, and Na+/H+ exchanger 3, as well as electrogenic glucose transport in the small intestine. In contrast, GRvillinCre mice did not respond to GC treatment, neither with regard to gene activation nor to glucose transport. GRdim mice were also refractory to GC, because dexamethasone treatment failed to increase both, gene expression and electrogenic glucose transport. In addition, the rise in blood glucose levels normally observed after GC administration was attenuated in both mutant mouse strains. We conclude that enhanced glucose transport in vivo primarily depends on gene regulation by the dimerized GR in enterocytes, and that this mechanism contributes to GC-induced hyperglycemia.

Functional Expression of Sodium-Dependent Glucose Transporter in Amelogenesis

2020 ◽  
Vol 99 (8) ◽  
pp. 977-986
Author(s):  
H. Ida-Yonemochi ◽  
K. Otsu ◽  
H. Harada ◽  
H. Ohshima
Keyword(s):  
Organ Culture ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Maturation Stage ◽  
Sodium Dependent ◽  
Tooth Morphogenesis

Glucose is an essential source of energy for mammalian cells and is transported into the cells by glucose transporters. There are 2 types of glucose transporters: one is a passive glucose transporter, GLUT ( SLC2A), and the other is a sodium-dependent active glucose transporter, SGLT ( SLC5A). We previously reported that the expression of GLUTs during tooth development is precisely and spatiotemporally controlled and that the glucose uptake mediated by GLUT1 plays a crucial role in early tooth morphogenesis and tooth size determination. This study aimed to clarify the localization and roles of SGLT1 and SGLT2 in murine ameloblast differentiation by using immunohistochemistry, immunoelectron microscopy, an in vitro tooth organ culture experiment, and in vivo administration of an inhibitor of SGLT1/2, phloridzin. SGLT1, which has high affinity with glucose, was immunolocalized in the early secretory ameloblasts and the ruffle-ended ameloblasts in the maturation stage. However, SGLT2, which has high glucose transport capacity, was observed in the stratum intermedium, papillary layer, and ameloblasts at the maturation stage and colocalized with Na+-K+-ATPase. The inhibition of SGLT1/2 by phloridzin in the tooth germs induced the disturbance of ameloblast differentiation and enamel matrix formation both in vitro (organ culture) and in vivo (mouse model). The expression of SGLT1 and SGLT2 was significantly upregulated in hypoxic conditions in the ameloblast-lineage cells. These findings suggest that the active glucose uptake mediated by SGLT1 and SGLT2 is strictly regulated and dependent on the intra- and extracellular microenvironments during tooth morphogenesis and that the appropriate passive and active glucose transport is an essential event in amelogenesis.

scholarly journals PPARγ-Independent Increase in Glucose Uptake and Adiponectin Abundance in Fat Cells

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3648-3660 ◽  
Author(s):  
Olga Dubuisson ◽  
Emily J. Dhurandhar ◽  
Rashmi Krishnapuram ◽  
Heather Kirk-Ballard ◽  
Alok K. Gupta ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glycemic Control ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Human Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Glucose Transporter 1

Although thiazolidinediones (TZD) effectively improve hyperglycemia and increase adiponectin, a proinsulin-sensitizing adipokine, they also increase adipogenesis via peroxisome proliferator-activated receptor (PPAR)γ induction, which may be undesirable. Recent safety concerns about some TZD have prompted the search for next generation agents that can enhance glycemic control and adiponectin independent of PPARγ or adipogenesis. Reminiscent of TZD action, a human adenovirus, adenovirus 36 (Ad36), up-regulates PPARγ, induces adipogenesis, and improves systemic glycemic control in vivo. We determined whether this effect of Ad36 requires PPARγ and/or adipogenesis. Glucose uptake and relevant cell signaling were determined in mock-infected or human adenoviruses Ad36 or Ad2-infected cell types under the following conditions: 1) undifferentiated human-adipose-tissue-derived stem cells (hASC), 2) hASC differentiated as adipocytes, 3) hASC in presence or absence of a PPARγ inhibitor, 4) NIH/3T3 that have impaired PPARγ expression, and 5) PPARγ-knockout mouse embryonic fibroblasts. Mouse embryonic fibroblasts with intact PPARγ served as a positive control. Additionally, to determine natural Ad36 infection, human sera were screened for Ad36 antibodies. In undifferentiated or differentiated hASC, or despite the inhibition, down-regulation, or the absence of PPARγ, Ad36 significantly enhanced glucose uptake and PPARγ, adiponectin, glucose transporter 4, and glucose transporter 1 protein abundance, compared with mock or Ad2-infected cells. This indicated that Ad36 up-regulates glucose uptake and adiponectin secretion independent of adipogenesis or without recruiting PPARγ. In humans, natural Ad36 infection predicted greater adiponectin levels, suggesting a human relevance of these effects. In conclusion, Ad36 provides a novel template to metabolically remodel human adipose tissue to enhance glycemic control without the concomitant increase in adiposity or PPARγ induction associated with TZD actions.

8-Bromo-cAMP inhibits glucose transport activity in mouse placental cells in culture

1996 ◽  
Vol 150 (2) ◽  
pp. 319-327 ◽  
Author(s):  
M Sakata ◽  
M Yamaguchi ◽  
T Imai ◽  
C Tadokoro ◽  
Y Yoshimoto ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Northern Blot ◽  
Glucose Transporter ◽  
Immunoblot Analysis ◽  
Transport Activity ◽  
Glucose Transporter 1 ◽  
Cells In Culture ◽  
Primary Mouse ◽  
Placental Cells

Abstract Glucose plays an important role in fetal development and energy metabolism. Facilitative glucose transporter-1 (GLUT1) has been found in placenta. However, little is known about GLUT1 modulation in placental cells. To examine changes in mouse placental GLUT1 levels caused by 8-bromo-cAMP, we performed 2-deoxyglucose uptake experiments, Northern blot analysis and immunoblot analysis using a primary mouse placental cell culture. Immunohistochemical analysis showed that GLUT1 was localized to the ectoplacental cone and the labyrinth zone of mouse placentas on days 7 and 11 of pregnancy respectively. Treatment of mouse placental cells with 250 μmol/l 8-bromo-cAMP resulted in a significant (P<0·01) decrease in glucose uptake on days 2–5 of culture. The inhibitory effect of 8-bromo-cAMP on glucose uptake was concentration-dependent. Glucose uptake was also inhibited by 100 μg/l cholera toxin and by 0·1 mmol/l forskolin. Northern blot and immunoblot analysis revealed that both GLUT1 mRNA and protein levels were also decreased by 8-bromo-cAMP. These findings suggest that 8-bromo-cAMP inhibits glucose transport activity in mouse placental cells in culture. Journal of Endocrinology (1996) 150, 319–327

Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice

2006 ◽  
Vol 291 (5) ◽  
pp. R1533-R1538 ◽  
Author(s):  
Ferruh Artunc ◽  
Rexhep Rexhepaj ◽  
Harald Völkl ◽  
Florian Grahammer ◽  
Christine Remy ◽  
...  
Keyword(s):  
Small Intestine ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Ussing Chamber ◽  
Glucose Absorption ◽  
Renal Tubules ◽  
Glucose Transporter 1 ◽  
Glucose Reabsorption ◽  
Urinary Glucose ◽  
Proximal Tubular

The phosphoinositide-dependent kinase-1 (PDK-1) activates the serum- and glucocorticoid-inducible kinase and protein kinase B isoforms, which, in turn, are known to stimulate the renal and intestinal Na+-dependent glucose transporter 1. The present study has been performed to explore the role of PDK-1 in electrogenic glucose transport in small intestine and proximal renal tubules. To this end, mice expressing ∼20% of PDK-1 ( pdk1 hm) were compared with their wild-type littermates ( pdk1 wt). According to Ussing chamber experiments, electrogenic glucose transport was significantly smaller in the jejunum of pdk1 hm than of pdk1 wt mice. Similarly, proximal tubular electrogenic glucose transport in isolated, perfused renal tubule segments was decreased in pdk1 hm compared with pdk1 wt mice. Intraperitoneal injection of 3 g/kg body wt glucose resulted in a similar increase of plasma glucose concentration in pdk1 hm and in pdk1 wt mice but led to a higher increase of urinary glucose excretion in pdk1 hm mice. In conclusion, reduction of functional PDK-1 leads to impairment of electrogenic intestinal glucose absorption and renal glucose reabsorption. The experiments disclose a novel element of glucose transport regulation in kidney and small intestine.

Glucagon-like peptide-2 protects against TPN-induced intestinal hexose malabsorption in enterally refed piglets

2006 ◽  
Vol 290 (2) ◽  
pp. G293-G300 ◽  
Author(s):  
J. J. Cottrell ◽  
B. Stoll ◽  
R. K. Buddington ◽  
J. E. Stephens ◽  
L. Cui ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Glucose Absorption ◽  
Glucose Transporter 1 ◽  
Portal Vein Flow ◽  
Glucose Transporter 2 ◽  
Glucagon Like Peptide ◽  
Portal Veins

Premature infants receiving chronic total parenteral nutrition (TPN) due to feeding intolerance develop intestinal atrophy and reduced nutrient absorption. Although providing the intestinal trophic hormone glucagon-like peptide-2 (GLP-2) during chronic TPN improves intestinal growth and morphology, it is uncertain whether GLP-2 enhances absorptive function. We placed catheters in the carotid artery, jugular and portal veins, duodenum, and a portal vein flow probe in piglets before providing either enteral formula (ENT), TPN or a coinfusion of TPN plus GLP-2 for 6 days. On postoperative day 7, all piglets were fed enterally and digestive functions were evaluated in vivo using dual infusion of enteral (13C) and intravenous (2H) glucose, in vitro by measuring mucosal lactase activity and rates of apical glucose transport, and by assessing the abundances of sodium glucose transporter-1 (SGLT-1) and glucose transporter-2 (GLUT2). Both ENT and GLP-2 pigs had larger intestine weights, longer villi, and higher lactose digestive capacity and in vivo net glucose and galactose absorption compared with TPN alone. These endpoints were similar in ENT and GLP-2 pigs except for a lower intestinal weight and net glucose absorption in GLP-2 compared with ENT pigs. The enhanced hexose absorption in GLP-2 compared with TPN pigs corresponded with higher lactose digestive and apical glucose transport capacities, increased abundance of SGLT-1, but not GLUT-2, and lower intestinal metabolism of [13C]glucose to [13C]lactate. Our findings indicate that GLP-2 treatment during chronic TPN maintains intestinal structure and lactose digestive and hexose absorptive capacities, reduces intestinal hexose metabolism, and may facilitate the transition to enteral feeding in TPN-fed infants.

scholarly journals Quercetin-3-O-glucoside Improves Glucose Tolerance in Rats and Decreases Intestinal Sugar Uptake in Caco-2 Cells

2017 ◽  
Vol 12 (11) ◽  
pp. 1934578X1701201 ◽  
Author(s):  
Denys Torres-Villarreal ◽  
Alberto Camacho ◽  
Fermín I. Milagro ◽  
Rocío Ortiz-Lopez ◽  
Ana Laura de la Garza
Keyword(s):  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
In Vivo Studies ◽  
Sugar Uptake ◽  
Oral Glucose ◽  
Rt Pcr ◽  
Glucose Transporter 1 ◽  
Glucose Transporter 2

Flavonoid-rich foods intake has been associated with lower risk of non-communicable chronic diseases. Quercetin is the most abundant flavonoid in nature (fruits, vegetables, leaves and grains) as well as the most consumed flavonol. This study aims to investigate the potential effects of its conjugated form quercetin-3- O-glucoside (or isoquercetin) on glucose metabolism in rats and Caco-2 cells. To analyse the effect of quercetin-3- O-glucoside on postprandial hyperglycemia, an oral glucose tolerance test (OGTT) was conducted in Wistar rats. Additionally, Caco-2 cells were used to determine the effect of quercetin-3- O-glucoside (30 to 60 μM) on mRNA expression of genes involved in glucose uptake by RT-PCR. Thereby, in vivo studies demonstrated that quercetin-3- O-glucoside decreased blood glucose levels evaluated by OGTT in rats. Furthermore, in the presence of Na+, quercetin-3- O-glucoside inhibited methylglucoside (MG) uptake in enterocytes and both sodium dependent glucose transporter-1 (SGLT1)- and glucose transporter-2 (GLUT2)-mediated glucose uptake were downregulated in Caco-2 cells incubated with quercetin-3- O-glucoside. In summary, our results show that quercetin-3- O-glucoside improves postprandial glycemic control in rats and reduces sugar uptake in Caco-2 cells, possible by decreasing the expression of glucose transporters (SGLT1 and GLUT2) according to the results obtained through RT-PCR.

scholarly journals Glucose-transporter (GLUT4) protein content in oxidative and glycolytic skeletal muscles from calf and goat

1995 ◽  
Vol 305 (2) ◽  
pp. 465-470 ◽  
Author(s):  
J F Hocquette ◽  
F Bornes ◽  
M Balage ◽  
P Ferre ◽  
J Grizard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Transporter Protein ◽  
Rat Muscle ◽  
Glucose Transporter Glut4

It is well accepted that skeletal muscle is a major glucose-utilizing tissue and that insulin is able to stimulate in vivo glucose utilization in ruminants as in monogastrics. In order to determine precisely how glucose uptake is controlled in various ruminant muscles, particularly by insulin, this study was designed to investigate in vitro glucose transport and insulin-regulatable glucose-transporter protein (GLUT4) in muscle from calf and goat. Our data demonstrate that glucose transport is the rate-limiting step for glucose uptake in bovine fibre strips, as in rat muscle. Insulin increases the rate of in vitro glucose transport in bovine muscle, but to a lower extent than in rat muscle. A GLUT4-like protein was detected by immunoblot assay in all insulin-responsive tissues from calf and goat (heart, skeletal muscle, adipose tissue) but not in liver, brain, erythrocytes and intestine. Unlike the rat, bovine and goat GLUT4 content is higher in glycolytic and oxido-glycolytic muscles than in oxidative muscles. In conclusion, using both a functional test (insulin stimulation of glucose transport) and an immunological approach, this study demonstrates that ruminant muscles express GLUT4 protein. Our data also suggest that, in ruminants, glucose is the main energy-yielding substrate for glycolytic but not for oxidative muscles, and that insulin responsiveness may be lower in oxidative than in other skeletal muscles.

scholarly journals A GSK-3/TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression

2008 ◽  
Vol 295 (3) ◽  
pp. C836-C843 ◽  
Author(s):  
Carolyn L. Buller ◽  
Robert D. Loberg ◽  
Ming-Hui Fan ◽  
Qihong Zhu ◽  
James L. Park ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Cell Types ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Glucose Transporter 1 ◽  
Glut1 Expression ◽  
Mutant Cells

Glucose transport is a highly regulated process and is dependent on a variety of signaling events. Glycogen synthase kinase-3 (GSK-3) has been implicated in various aspects of the regulation of glucose transport, but the mechanisms by which GSK-3 activity affects glucose uptake have not been well defined. We report that basal glycogen synthase kinase-3 (GSK-3) activity regulates glucose transport in several cell types. Chronic inhibition of basal GSK-3 activity (8–24 h) in several cell types, including vascular smooth muscle cells, resulted in an approximately twofold increase in glucose uptake due to a similar increase in protein expression of the facilitative glucose transporter 1 (GLUT1). Conversely, expression of a constitutively active form of GSK-3β resulted in at least a twofold decrease in GLUT1 expression and glucose uptake. Since GSK-3 can inhibit mammalian target of rapamycin (mTOR) signaling via phosphorylation of the tuberous sclerosis complex subunit 2 (TSC2) tumor suppressor, we investigated whether chronic GSK-3 effects on glucose uptake and GLUT1 expression depended on TSC2 phosphorylation and TSC inhibition of mTOR. We found that absence of functional TSC2 resulted in a 1.5-to 3-fold increase in glucose uptake and GLUT1 expression in multiple cell types. These increases in glucose uptake and GLUT1 levels were prevented by inhibition of mTOR with rapamycin. GSK-3 inhibition had no effect on glucose uptake or GLUT1 expression in TSC2 mutant cells, indicating that GSK-3 effects on GLUT1 and glucose uptake were mediated by a TSC2/mTOR-dependent pathway. The effect of GSK-3 inhibition on GLUT1 expression and glucose uptake was restored in TSC2 mutant cells by transfection of a wild-type TSC2 vector, but not by a TSC2 construct with mutated GSK-3 phosphorylation sites. Thus, TSC2 and rapamycin-sensitive mTOR function downstream of GSK-3 to modulate effects of GSK-3 on glucose uptake and GLUT1 expression. GSK-3 therefore suppresses glucose uptake via TSC2 and mTOR and may serve to match energy substrate utilization to cellular growth.

scholarly journals Regulation of GLUT1-mediated glucose uptake by PKCλ–PKCβII interactions in 3T3-L1 adipocytes

2004 ◽  
Vol 384 (2) ◽  
pp. 349-355 ◽  
Author(s):  
Remko R. BOSCH ◽  
Merlijn BAZUINE ◽  
Paul N. SPAN ◽  
Peter H. G. M. WILLEMS ◽  
André J. OLTHAAR ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Mitogen Activated Protein Kinase ◽  
Glucose Transporter 1 ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
Pkc Protein Kinase C

Members of the PKC (protein kinase C) superfamily play key regulatory roles in glucose transport. How the different PKC isotypes are involved in the regulation of glucose transport is still poorly defined. PMA is a potent activator of conventional and novel PKCs and PMA increases the rate of glucose uptake in many different cell systems. In the present study, we show that PMA treatment increases glucose uptake in 3T3-L1 adipocytes by two mechanisms: a mitogen-activated protein kinase kinase-dependent increase in GLUT1 (glucose transporter 1) expression levels and a PKCλ-dependent translocation of GLUT1 towards the plasma membrane. Intriguingly, PKCλ co-immunoprecipitated with PKCβII and did not with PKCβI. Previously, we have described that down-regulation of PKCβII protein levels or inhibiting PKCβII by means of the myristoylated PKCβC2–4 peptide inhibitor induced GLUT1 translocation towards the plasma membrane in 3T3-L1 adipocytes. Combined with the present findings, these results suggest that the liberation of PKCλ from PKCβII is an important factor in the regulation of GLUT1 distribution in 3T3-L1 adipocytes.

scholarly journals INSULIN GROWTH FACTOR I AND ITS RECEPTOR ARE ANTAGONISTIC MODULATORS OF GLUCOSE HANDLING BY ASTROCYTES

2015 ◽  
Author(s):  
Edwin Hernandez ◽  
Ana M Fernandez ◽  
Alberto Perez Alvarez ◽  
Sara Mederos ◽  
Paloma Perez Domper ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Brain Slices ◽  
Glucose Transporter 1 ◽  
Factor I ◽  
Igf I ◽  
Pharmacological Blockade ◽  
Growth Factor I

Reducing insulin-like growth factor I receptor (IGF-IR) levels or administration of IGF-I show beneficial effects in the brain. We now provide evidence to help resolve this paradox. The unliganded IGF-IR inhibits glucose uptake by astrocytes while its stimulation with IGF-I, in concert with insulin activation of the insulin receptor, produces the opposite effect. In vivo imaging showed that shRNA interference of brain IGF-IR increased glucose uptake by astrocytes while pharmacological blockade of IGF-IR reduced it. Brain 18FGlucose-PET of IGF-IR shRNA injected mice confirmed an inhibitory role of unliganded IGF-IR on glucose uptake, whereas glucose-dependent recovery of neuronal activity in brain slices was blunted by pharmacological blockade of IGF-IR. Mechanistically, we found that the unliganded IGF-IR retains glucose transporter 1 (GLUT1), the main glucose transporter in astrocytes, inside the cell while IGF-I, in cooperation with insulin, synergistically stimulates MAPK/PKD to promote association of IGF-IR with GLUT 1 via Rac1/GIPC1 and increases GLUT1 availability at the cell membrane. These findings identify IGF-I and its receptor as antagonistic modulators of brain glucose uptake.

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