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 Estriol blunts postprandial blood glucose rise in male rats through regulating intestinal glucose transporters

2015 ◽  
Vol 308 (5) ◽  
pp. E370-E379 ◽  
Author(s):  
Noriko Yamabe ◽  
Ki Sung Kang ◽  
Woojung Lee ◽  
Su-Nam Kim ◽  
Bao Ting Zhu
Keyword(s):  
Blood Glucose ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Male Rats ◽  
Postprandial Blood Glucose ◽  
Oral Glucose ◽  
Glucose Transporter 1 ◽  
Glucose Transporter 2 ◽  
17Β Estradiol

Despite increased total food intake in healthy, late-stage pregnant women, their peak postprandial blood sugar levels are normally much lower than the levels seen in healthy nonpregnant women. In this study, we sought to determine whether estriol (E3), an endogenous estrogen predominantly produced during human pregnancy, contributes to the regulation of the postprandial blood glucose level in healthy normal rats. In vivo studies using rats showed that E3 blunted the speed and magnitude of the blood glucose rise following oral glucose administration, but it did not appear to affect the total amount of glucose absorbed. E3 also did not affect insulin secretion, but it significantly reduced the rate of intestinal glucose transport compared with vehicle-treated animals. Consistent with this finding, expression of the sodium-dependent glucose transporter 1 and 2 was significantly downregulated by E3 treatment in the brush-border membrane and basolateral membrane, respectively, of enterocytes. Most of the observed in vivo effects were noticeably stronger with E3 than with 17β-estradiol. Using differentiated human Caco-2 enterocyte monolayer culture as an in vitro model, we confirmed that E3 at physiologically relevant concentrations could directly inhibit glucose uptake via suppression of glucose transporter 2 expression, whereas 17β-estradiol did not have a similar effect. Collectively, these data showed that E3 can blunt the postprandial glycemic surge in rats through modulating the level of intestinal glucose transporters.

scholarly journals Ecklonia cavaInhibits Glucose Absorption and Stimulates Insulin Secretion in Streptozotocin-Induced Diabetic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Kyung Kim
Keyword(s):  
Insulin Secretion ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Islet Cells ◽  
Glucose Absorption ◽  
Oral Glucose ◽  
Diabetic Mice ◽  
Glucose Transporter 1

Aims of study. Present study investigated the effect ofEcklonia cava(EC) on intestinal glucose uptake and insulin secretion.Materials and methods. Intestinal Na+-dependent glucose uptake (SGU) and Na+-dependent glucose transporter 1 (SGLT1) protein expression was determined using brush border membrane vesicles (BBMVs). Glucose-induced insulin secretion was examined in pancreatic β-islet cells. The antihyperglycemic effects of EC, SGU, and SGLT1 expression were determined in streptozotocin (STZ)-induced diabetic mice.Results. Methanol extract of EC markedly inhibited intestinal SGU of BBMV with the IC50value of 345 μg/mL. SGLT1 protein expression was dose dependently down regulated with EC treatment. Furthermore, insulinotrophic effect of EC extract was observed at high glucose media in isolated pancreatic β-islet cellsin vitro. We next conducted the antihyperglycemic effect of EC in STZ-diabetic mice. EC supplementation markedly suppressed SGU and SGLT1 abundance in BBMV from STZ mice. Furthermore, plasma insulin level was increased by EC treatment in diabetic mice. As a result, EC supplementation improved postprandial glucose regulation, assessed by oral glucose tolerance test, in diabetic mice.Conclusion. These results suggest that EC play a role in controlling dietary glucose absorption at the intestine and insulinotrophic action at the pancreas contributing blood glucose homeostasis in diabetic condition.

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.

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.

scholarly journals Insulin-regulated aminopeptidase inhibitors do not alter glucose handling in normal and diabetic rats

2017 ◽  
Vol 58 (4) ◽  
pp. 193-198 ◽  
Author(s):  
Anthony L Albiston ◽  
Mauricio Cacador ◽  
Puspha Sinnayah ◽  
Peta Burns ◽  
Siew Yeen Chai
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Specific Inhibitor ◽  
Diabetic Rats ◽  
Whole Body ◽  
Aminopeptidase Activity ◽  
Oral Glucose ◽  
Glucose Challenge

Insulin-regulated aminopeptidase (IRAP) co-localizes with the glucose transporter 4 (GLUT4) in GLUT4 storage vesicles (GSV) in insulin-responsive cells. In response to insulin, IRAP is the only transmembrane enzyme known to translocate together with GLUT4 to the plasma membrane in adipocytes and muscle cells. Although the intracellular region of IRAP is associated with GLUT4 vesicle trafficking, the role of the aminopeptidase activity in insulin-responsive cells has not been elucidated. The aim of this study was to investigate whether the inhibition of the aminopeptidase activity of IRAP facilitates glucose uptake in insulin-responsive cells. In both in vitro and in vivo studies, inhibition of IRAP aminopeptidase activity with the specific inhibitor, HFI-419, did not modulate glucose uptake. IRAP inhibition in the L6GLUT4myc cell line did not alter glucose uptake in both basal and insulin-stimulated state. In keeping with these results, HFI419 did not affect peripheral, whole-body glucose handling after an oral glucose challenge, neither in normal rats nor in the streptozotocin (STZ)-induced experimental rat model of diabetes mellitus (DM). Therefore, acute inhibition of IRAP aminopeptidase activity does not affect glucose homeostasis.

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 Glucose transporter 2 concentrations in hyper- and hypothyroid rat livers

1999 ◽  
Vol 160 (2) ◽  
pp. 285-289 ◽  
Author(s):  
T Mokuno ◽  
K Uchimura ◽  
R Hayashi ◽  
N Hayakawa ◽  
M Makino ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Abnormal Glucose Metabolism ◽  
Glucose Transporter 2 ◽  
Liver And Pancreas ◽  
Rat Livers

The deterioration of glucose metabolism frequently observed in hyperthyroidism may be due in part to increased gluconeogenesis in the liver and glucose efflux through hepatocyte plasma membranes. Glucose transporter 2 (GLUT 2), a facilitative glucose transporter localized to the liver and pancreas, may play a role in this distorted glucose metabolism. We examined changes in the levels of GLUT 2 in livers from rats with l-thyroxine-induced hyperthyroidism or methimazole-induced hypothyroidism by using Western blotting to detect GLUT 2. An oral glucose tolerance test revealed an oxyhyperglycemic curve (impaired glucose tolerance) in hyperthyroid rats (n=7) and a flattened curve in hypothyroid rats (n=7). GLUT 2 levels in hepatocyte plasma membranes were significantly increased in hyperthyroid rats and were not decreased in hypothyroid rats compared with euthyroid rats. The same results were obtained with a densitometric assay. These findings suggest that changes in the liver GLUT 2 concentration may contribute to abnormal glucose metabolism in thyroid disorders.

scholarly journals Discovery and Development of Inhibitors of the Plasmodial FNT-Type Lactate Transporter as Novel Antimalarials

2021 ◽  
Vol 14 (11) ◽  
pp. 1191
Author(s):  
Cornelius Nerlich ◽  
Nathan H. Epalle ◽  
Philip Seick ◽  
Eric Beitz
Keyword(s):  
Glucose Transporter ◽  
Resistance Mutation ◽  
In Vivo Studies ◽  
Glucose Transporter 1 ◽  
Transporter Family ◽  
Glucose Molecule ◽  
Lactate Transporter ◽  
Further Development ◽  
Glucose Supply

Plasmodium spp. malaria parasites in the blood stage draw energy from anaerobic glycolysis when multiplying in erythrocytes. They tap the ample glucose supply of the infected host using the erythrocyte glucose transporter 1, GLUT1, and a hexose transporter, HT, of the parasite’s plasma membrane. Per glucose molecule, two lactate anions and two protons are generated as waste that need to be released rapidly from the parasite to prevent blockage of the energy metabolism and acidification of the cytoplasm. Recently, the missing Plasmodium lactate/H+ cotransporter was identified as a member of the exclusively microbial formate–nitrite transporter family, FNT. Screening of an antimalarial compound selection with unknown targets led to the discovery of specific and potent FNT-inhibitors, i.e., pentafluoro-3-hydroxy-pent-2-en-1-ones. Here, we summarize the discovery and further development of this novel class of antimalarials, their modes of binding and action, circumvention of a putative resistance mutation of the FNT target protein, and suitability for in vivo studies using animal malaria models.

Lumenal adenosine and AMP rapidly increase glucose transport by intact small intestine

2005 ◽  
Vol 289 (6) ◽  
pp. G1007-G1014 ◽  
Author(s):  
Yasuhiro Kimura ◽  
Jerrold R. Turner ◽  
Dwaine A. Braasch ◽  
Randal K. Buddington
Keyword(s):  
Receptor Antagonist ◽  
Glucose Uptake ◽  
Clinical Relevance ◽  
Glucose Transporter ◽  
Disodium Salt ◽  
Systemic Availability ◽  
Intracellular Camp ◽  
Glucose Transporter 1 ◽  
Glucose Transporter 2 ◽  
Physiological Dose

Adenosine modulates the intestinal functions of secretion, motility, and immunity, yet little is known about the regulation of nutrient absorption. Therefore, we measured the carrier-mediated uptake of tracer d-[14C]glucose (2 μM) by everted sleeves of the mouse intestine after a lumenal exposure to adenosine and a disodium salt of AMP. Rates of glucose uptake by intact tissues increased almost twofold after a 7-min exposure to 5 mM adenosine (a physiological dose). The response was slightly more pronounced for AMP and could be induced by forskolin. The response to adenosine was blocked by theophylline and the A2 receptor antagonist 3,7-dimethyl-1-proparglyxanthine but not by the A1 receptor antagonist 8-phenyltheophylline. Glucose uptake by control and AMP-stimulated tissues was inhibited by phloridzin, implying that sodium-dependent glucose transporter 1 (SGLT1) is the responsive transporter, but the involvement of glucose transporter 2 (GLUT2) cannot be excluded. Of clinical relevance, AMP accelerated the systemic availability of 3- O-methylglucose after an oral administration to mice. Our results indicate that adenosine causes a rapid increase in carrier-mediated glucose uptake that is of clinical relevance and acts via receptors linked to a signaling pathway that involves intracellular cAMP production.

scholarly journals Glutamate increases glucose uptake in L6 myotubes in a concentration- and time-dependent manner that is mediated by AMPK

2018 ◽  
Vol 43 (12) ◽  
pp. 1307-1313 ◽  
Author(s):  
Tyler Barnes ◽  
Katie M. Di Sebastiano ◽  
Filip Vlavcheski ◽  
Joe Quadrilatero ◽  
Evangelia Litsa Tsiani ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Serum Insulin ◽  
Insulin Response ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
L6 Myotubes ◽  
Compound C ◽  
Carbohydrate Load

Various in vivo studies have investigated the insulin response that is elicited when glutamate is elevated in circulation or in a given tissue; fewer studies have investigated the effects of glutamate on glucose uptake and handling. Glutamate ingestion in humans can attenuate rises in blood glucose following a carbohydrate load in the absence of increases in serum insulin concentrations. However, the underlying mechanisms have yet to be investigated. To elucidate the effects of glutamate on glucose handling in skeletal muscle tissue, differentiated rat L6 myocytes were treated with glutamate, and glucose uptake was assessed with the use of 2-[3H]-deoxy-d-glucose ([3H]-2-DG). Cells treated with 2 mmol/L glutamate experienced the greatest increase in [3H]-2-DG uptake relative to the control condition (177% ± 2% of control, P < 0.001) and the uptake was similar to that of metformin (184% ± 4%, P < 0.001). In line with these findings, differentiated glucose transporter 4 (GLUT4)-overexpressing myotubes treated with 2 mmol/L glutamate displayed significantly increased GLUT4 translocation when compared with the control condition (159% ± 8% of control, P < 0.001) and to an extent similar to that of insulin and metformin (181% ± 7% and 159% ± 12%, respectively). An AMP-activated protein kinase (AMPK) inhibitor (Compound C) abolished the glutamate-stimulated glucose uptake (98% ± 12% of control), and Western blotting revealed significantly elevated AMPK phosphorylation (278% ± 17% of control, P < 0.001) by glutamate. Our findings suggest that when muscle cells are exposed to increased glutamate concentrations, glucose uptake into these cells is augmented through AMPK activation, through mechanisms distinct from those of insulin and leucine.

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