scholarly journals Adiponectin stimulates glucose uptake in mouse blastocysts and embryonic carcinoma cells

Reproduction ◽  
2020 ◽  
Vol 159 (3) ◽  
pp. 227-239
Author(s):  
J Burkuš ◽  
A Navarrete Santos ◽  
M Schindler ◽  
J Babeľová ◽  
J S Jung ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
P38 Mapk ◽  
Glucose Transporter ◽  
Embryoid Bodies ◽  
Full Length ◽  
Preimplantation Embryos ◽  
Embryonic Cells ◽  
Mapk Phosphorylation ◽  
Embryonic Carcinoma ◽  
Globular Adiponectin

Preimplantation embryos are sensitive to maternal hormones affecting embryonic signal transduction and metabolic functions. We examined whether adiponectin, the most abundantly secreted adipokine, can influence glucose transport in mouse embryonic cells. In mouse blastocysts full-length adiponectin stimulated glucose uptake, while no effect of globular adiponectin was found. Full-length adiponectin stimulated translocation of GLUT8 glucose transporter to the cell membrane; we did not detect significant changes in the intracellular localization of GLUT4 glucose transporter in adiponectin-treated blastocysts. To study adiponectin signaling in detail, we used embryoid bodies formed from mouse embryonic carcinoma cell (ECC) line P19. We confirmed the expression of adiponectin receptors in these cells. Similar to mouse blastocysts, full-length adiponectin, but not globular adiponectin, stimulated glucose uptake in ECC P19 embryoid bodies. Moreover, full-length adiponectin stimulated AMPK and p38 MAPK phosphorylation. These results indicate that besides AMPK, p38 MAPK is a potential target of adiponectin in mouse embryonic cells. AMPK inhibitor did not influence the adiponectin-stimulated p38 MAPK phosphorylation, indicating independent action of these two signaling pathways. In mouse embryos adiponectin acts as a hormonal regulator of glucose uptake, which becomes especially important in phases with reduced levels of circulating insulin. Our results suggest that adiponectin maintains the glucose supply for early embryos under hypoinsulinaemic conditions, for example, in mothers suffering from type 1 diabetes mellitus.

scholarly journals Glucose uptake inhibition decreases expressions of receptor activator of nuclear factor-kappa B ligand (RANKL) and osteocalcin in osteocytic MLO-Y4-A2 cells

2018 ◽  
Vol 314 (2) ◽  
pp. E115-E123 ◽  
Author(s):  
Ayumu Takeno ◽  
Ippei Kanazawa ◽  
Masakazu Notsu ◽  
Ken-ichiro Tanaka ◽  
Toshitsugu Sugimoto
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
P38 Mapk ◽  
Glucose Transporter ◽  
Mek Inhibitor ◽  
Long Bone ◽  
Uptake Inhibition ◽  
Glucose Transporter 1 ◽  
P38 Inhibitor ◽  
Glucose Levels

Bone and glucose metabolism are closely associated with each other. Both osteoblast and osteoclast functions are important for the action of osteocalcin, which plays pivotal roles as an endocrine hormone regulating glucose metabolism. However, it is unknown whether osteocytes are involved in the interaction between bone and glucose metabolism. We used MLO-Y4-A2, a murine long bone-derived osteocytic cell line, to investigate effects of glucose uptake inhibition on expressions of osteocalcin and bone-remodeling modulators in osteocytes. We found that glucose transporter 1 (GLUT1) is expressed in MLO-Y4-A2 cells and that treatment with phloretin, a GLUT inhibitor, significantly inhibited glucose uptake. Real-time PCR and Western blot showed that phloretin significantly and dose-dependently decreased the expressions of RANKL and osteocalcin, whereas osteoprotegerin or sclerostin was not affected. Moreover, phloretin activated AMP-activated protein kinase (AMPK), an intracellular energy sensor. Coincubation of ara-A, an AMPK inhibitor, with phloretin canceled the phloretin-induced decrease in osteocalcin expression, but not RANKL. In contrast, phloretin suppressed phosphorylation of ERK1/2, JNK, and p38 MAPK, and treatments with the p38 inhibitor SB203580 and the MEK inhibitor PD98059, but not the JNK inhibitor SP600125, significantly decreased expressions of RANKL and osteocalcin. These results indicate that glucose uptake by GLUT1 is required for RANKL and osteocalcin expressions in osteocytes, and that inhibition of glucose uptake decreases their expressions through AMPK, ERK1/2, and p38 MAPK pathways. These findings suggest that lowering glucose uptake into osteocytes may contribute to maintain blood glucose levels by decreasing osteocalcin expression and RANKL-induced bone resorption.

Prior exercise increases basal and insulin-induced p38 mitogen-activated protein kinase phosphorylation in human skeletal muscle

2003 ◽  
Vol 94 (6) ◽  
pp. 2337-2341 ◽  
Author(s):  
Farah S. L. Thong ◽  
Wim Derave ◽  
Birgitte Ursø ◽  
Bente Kiens ◽  
Erik A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
P38 Mapk ◽  
Human Skeletal Muscle ◽  
Insulin Infusion ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Phosphorylation ◽  
Prior Exercise ◽  
Mitogen Activated Protein

We have examined the effects of insulin on p38 mitogen-activated protein kinase (MAPK) phosphorylation in human skeletal muscle and the effects of prior exercise hereon. Seven men performed 1-h one-legged knee extensor exercise 3 h before the initiation of a 100-min euglycemic-hyperinsulinemic (600 pmol/l) clamp. Glucose uptake across the legs was measured with the leg balance technique, and muscle biopsies were obtained from the rested and exercised vastus lateralis before and during insulin infusion. Net glucose uptake during the clamp was ∼50% higher ( P< 0.05) in the exercised leg than in the rested leg. Insulin induced a modest sustained 1.2- and 1.3-fold increase ( P < 0.05) in p38 MAPK phosphorylation in the rested and exercised legs, respectively. However, p38 phosphorylation was ∼50% higher ( P < 0.05) in the exercised compared with the rested leg before and during insulin infusion. We conclude that a physiological concentration of insulin causes modest but sustained activation of the p38 MAPK pathway in human skeletal muscle. Furthermore, the stimulatory effect of exercise on p38 phosphorylation is persistent for at least 3 h after exercise and remains evident during subsequent insulin stimulation. Because p38 MAPK has been suggested to play a necessary role in activation of GLUT-4 at the cell surface, the present data may suggest a putative role of p38 MAPK in the increased insulin sensitivity of skeletal muscle after exercise.

scholarly journals MKK6/3 and p38 MAPK Pathway Activation Is Not Necessary for Insulin-induced Glucose Uptake but Regulates Glucose Transporter Expression

2001 ◽  
Vol 276 (23) ◽  
pp. 19800-19806 ◽  
Author(s):  
Midori Fujishiro ◽  
Yukiko Gotoh ◽  
Hideki Katagiri ◽  
Hideyuki Sakoda ◽  
Takehide Ogihara ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
P38 Mapk ◽  
Glucose Transporter ◽  
Mapk Pathway ◽  
P38 Mapk Pathway ◽  
Pathway Activation ◽  
Transporter Expression

scholarly journals Expression of glucose transporter and glucose uptake in human oocytes and preimplantation embryos

1997 ◽  
Vol 12 (11) ◽  
pp. 2508-2510 ◽  
Author(s):  
M. Dan-Goor ◽  
S. Sasson ◽  
A. Davarashvili ◽  
M. Almagor
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Preimplantation Embryos ◽  
Human Oocytes

scholarly journals Adenosine 5′-Monophosphate-Activated Protein Kinase and p38 Mitogen-Activated Protein Kinase Participate in the Stimulation of Glucose Uptake by Dinitrophenol in Adult Cardiomyocytes

Endocrinology ◽  
2005 ◽  
Vol 146 (5) ◽  
pp. 2285-2294 ◽  
Author(s):  
Amélie Pelletier ◽  
Érik Joly ◽  
Marc Prentki ◽  
Lise Coderre
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Primary Cultures ◽  
Metabolic Stress ◽  
Mapk Signaling ◽  
Mapk Phosphorylation ◽  
Adult Cardiomyocytes ◽  
Stimulation Of

Abstract During metabolic stress, such as ischemia or hypoxia, glucose becomes the principal energy source for the heart. It has been shown that increased cardiac glucose uptake during metabolic stress has a protective effect on cell survival and heart function. Despite its physiological importance, only limited data are available on the molecular mechanisms regulating glucose uptake under these conditions. We used 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, as a model to mimic hypoxia and gain insight into the signaling pathway underlying metabolic stress-induced glucose uptake in primary cultures of rat adult cardiomyocytes. The results demonstrate that 0.1 mm DNP induces 2.2- and 9-fold increases in AMP-activated protein kinase (AMPK) and p38 MAPK phosphorylation, respectively. This is associated with a 2.3-fold increase in glucose uptake in these cells. To further delineate the role of AMPK in the regulation of glucose uptake, we used two complementary approaches: pharmacological inhibition of the enzyme with adenine 9-β-D arabinofuranoside and adenoviral infection with a dominant-negative AMPK (DN-AMPK) mutant. Our results show that overexpression of DN-AMPK completely suppressed DNP-mediated phosphorylation of acetyl coenzyme A carboxylase, a downstream target of AMPK. Inhibition of AMPK with either 9-β-D arabinofuranoside or DN-AMPK also abolished DNP-mediated p38 MAPK phosphorylation. Importantly, AMPK inhibition only partially decreased DNP-stimulated glucose uptake in cardiomyocytes. Inhibition of p38 MAPK with the pharmacological agent PD169316 also partially reduced (70%) glucose uptake in response to DNP. In conclusion, our results indicate that p38 MAPK acts downstream of AMPK in cardiomyocytes and that activation of the AMPK/p38 MAPK signaling cascade is essential for maximal stimulation of glucose uptake in response to DNP in adult cardiomyocytes.

scholarly journals Two insulin-responsive glucose transporter isoforms and the insulin receptor are developmentally expressed in rabbit preimplantation embryos

Reproduction ◽  
2004 ◽  
Vol 128 (5) ◽  
pp. 503-516 ◽  
Author(s):  
Anne Navarrete Santos ◽  
Sarah Tonack ◽  
Michaela Kirstein ◽  
Silke Kietz ◽  
Bernd Fischer
Keyword(s):  
Insulin Receptor ◽  
Western Blotting ◽  
Glucose Transporter ◽  
Preimplantation Embryos ◽  
Embryonic Cells ◽  
Coding Region ◽  
Rt Pcr ◽  
Early Embryos ◽  
Perinuclear Cytoplasm ◽  
Race Pcr

Glucose is the most important energy substrate for mammalian blastocysts. Its uptake is mediated by glucose transporters (GLUT). In muscle and adipocyte cells insulin stimulates glucose uptake by activation of the insulin receptor (IR) pathway and translocation of GLUT4. GLUT4 is expressed in bovine preimplantation embryos. A new insulin-responsive isoform, GLUT8, was recently described in mouse blastocysts. Thus, potentially, two insulin-responsive isoforms are expressed in early embryos. The mechanism of insulin action on embryonic cells, however, is still not clear. In the present study expression of IR, GLUT1, 2, 3, 4, 5 and 8 was studied in rabbit preimplantation embryos using RT-PCR, Western blotting and immunohistochemistry. The rabbit mRNA sequences for the complete coding region of IR, GLUT4 and a partial GLUT8 sequence were determined by RACE-PCR and sequencing. GLUT4 was expressed in 3-day-old morulae and in 4- and 6-day-old blastocysts. IR and GLUT8 transcripts were detectable only in blastocysts. Blastocysts also expressed GLUT1 and 3, but not GLUT2 and 5. Transcript numbers of GLUT4 and 8 were higher in trophoblast than in embryoblast cells. Translation of IR, GLUT4 and 8 proteins in blastocysts was confirmed by Western blotting. GLUT4 was localized mainly in the membrane and in the perinuclear region in trophoblast cells while in embryoblast cells its localization was predominantly in the perinuclear cytoplasm. The possible function(s) of two insulin-responsive isoforms, GLUT4 and GLUT8, in rabbit preimplantation embryos needs further investigation. It may not necessarily be linked to insulin-stimulated glucose transport.

Activation of the glucose transporter GLUT4 by insulin

2002 ◽  
Vol 80 (5) ◽  
pp. 569-578 ◽  
Author(s):  
L Michelle Furtado ◽  
Romel Somwar ◽  
Gary Sweeney ◽  
Wenyan Niu ◽  
Amira Klip
Keyword(s):  
Glucose Uptake ◽  
P38 Mapk ◽  
Glucose Transporter ◽  
Mitogen Activated Protein Kinase ◽  
Intrinsic Activity ◽  
Glut4 Translocation ◽  
Glucose Transporter 4 ◽  
Mitogen Activated Protein ◽  
In Series ◽  
Glucose Transporter Glut4

The transport of glucose into cells and tissues is a highly regulated process, mediated by a family of facilitative glucose transporters (GLUTs). Insulin-stimulated glucose uptake is primarily mediated by the transporter isoform GLUT4, which is predominantly expressed in mature skeletal muscle and fat tissues. Our recent work suggests that two separate pathways are initiated in response to insulin: (i) to recruit transporters to the cell surface from intracellular pools and (ii) to increase the intrinsic activity of the transporters. These pathways are differentially inhibited by wortmannin, demonstrating that the two pathways do not operate in series. Conversely, inhibitors of p38 mitogen-activated protein kinase (MAPK) imply that p38 MAPK is involved only in the regulation of the pathway leading to the insulin-stimulated activation of GLUT4. This review discusses the evidence for the divergence of GLUT4 translocation and activity and proposed mechanisms for the regulation of GLUT4.Key words: glucose transporter 4 (GLUT4), glucose uptake, p38 MAPK, GLUT4 activity.

scholarly journals LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Monira Obaid ◽  
S. M. Nashir Udden ◽  
Prasanna Alluri ◽  
Subhrangsu S. Mandal
Keyword(s):  
Immune Response ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Immune Cells ◽  
Glucose Transporter ◽  
Energy Needs ◽  
Glut1 Expression ◽  
Lncrna Hotair ◽  
Upstream Regulators ◽  
Glucose Transporter Glut1

AbstractInflammation plays central roles in the immune response. Inflammatory response normally requires higher energy and therefore is associated with glucose metabolism. Our recent study demonstrates that lncRNA HOTAIR plays key roles in NF-kB activation, cytokine expression, and inflammation. Here, we investigated if HOTAIR plays any role in the regulation of glucose metabolism in immune cells during inflammation. Our results demonstrate that LPS-induced inflammation induces the expression of glucose transporter isoform 1 (Glut1) which controls the glucose uptake in macrophages. LPS-induced Glut1 expression is regulated via NF-kB activation. Importantly, siRNA-mediated knockdown of HOTAIR suppressed the LPS-induced expression of Glut1 suggesting key roles of HOTAIR in LPS-induced Glut1 expression in macrophage. HOTAIR induces NF-kB activation, which in turn increases Glut1 expression in response to LPS. We also found that HOTAIR regulates glucose uptake in macrophages during LPS-induced inflammation and its knockdown decreases LPS-induced increased glucose uptake. HOTAIR also regulates other upstream regulators of glucose metabolism such as PTEN and HIF1α, suggesting its multimodal functions in glucose metabolism. Overall, our study demonstrated that lncRNA HOTAIR plays key roles in LPS-induced Glut1 expression and glucose uptake by activating NF-kB and hence HOTAIR regulates metabolic programming in immune cells potentially to meet the energy needs during the immune response.

Differential glycolytic and glycogenogenic transduction pathways in male and female bovine embryos produced in vitro

2012 ◽  
Vol 24 (2) ◽  
pp. 344 ◽  
Author(s):  
M. Garcia-Herreros ◽  
I. M. Aparicio ◽  
D. Rath ◽  
T. Fair ◽  
P. Lonergan
Keyword(s):  
Glucose Metabolism ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Bovine Embryos ◽  
High Concentration ◽  
Glucose Transporter 1 ◽  
Male And Female ◽  
Glut 1

Previous studies have shown that developmental kinetic rates following IVF are lower in female than in male blastocysts and that this may be related to differences in glucose metabolism. In addition, an inhibition of phosphatidylinositol 3-kinase (PI3-K) inhibits glucose uptake in murine blastocysts. Therefore, the aim of this study was to identify and compare the expression of proteins involved in glucose metabolism (hexokinase-I, HK-I; phosphofructokinase-1, PFK-1; pyruvate kinase1/2, PK1/2; glyceraldehyde-3-phosphate dehydrogenase, GAPDH; glucose transporter-1, GLUT-1; and glycogen synthase kinase-3, GSK-3) in male and female bovine blastocysts to determine whether PI3-K has a role in the regulation of the expression of these proteins. Hexokinase-I, PFK-1, PK1/2, GAPDH and GLUT-1 were present in bovine embryos. Protein expression of these proteins and GSK-3 was significantly higher in male compared with female blastocysts. Inhibition of PI3-K with LY294002 significantly decreased the expression of HK-I, PFK-1, GAPDH, GSK-3 A/B and GLUT-1. Results showed that the expression of glycolytic proteins HK-I, PFK-1, GAPDH and PK1/2, and the transporters GLUT-1 and GSK-3 is regulated by PI3-K in bovine blastocysts. Moreover, the differential protein expression observed between male and female blastocysts might explain the faster developmental kinetics seen in males, as the expression of main proteins involved in glycolysis and glycogenogenesis was significantly higher in male than female bovine embryos and also could explain the sensitivity of male embryos to a high concentration of glucose, as a positive correlation between GLUT-1 expression and glucose uptake in embryos has been demonstrated.

scholarly journals Somatostatin stimulates intestinal NHE8 expression via p38 MAPK pathway

2011 ◽  
Vol 300 (2) ◽  
pp. C375-C382 ◽  
Author(s):  
Chunhui Wang ◽  
Hua Xu ◽  
Huacong Chen ◽  
Jing Li ◽  
Bo Zhang ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mapk Pathway ◽  
Somatostatin Receptor ◽  
Peptide Hormone ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Phosphorylation ◽  
P38 Mapk Pathway ◽  
Mitogen Activated Protein ◽  
D Cells ◽  
Human Intestinal Cells

Diarrhea is a common manifestation of gastrointestinal disorders. Diarrhea-induced losses of fluid and electrolyte could lead to dehydration and electrolyte imbalances, resulting in significant morbidity and mortality, especially in children living in developing countries. Somatostatin, a peptide hormone secreted by D-cells, plays an important role in regulating motility and intestinal Na+ absorption. Although octreotide, a somatostatin analog, is used to treat diarrhea, its mechanisms of action are unclear. Here we showed that octreotide increased brush-border membrane Na+/H+ exchanger 8 (NHE8) expression in the small intestine to the exclusion of other NHEs that participate in Na+ absorption. The same effect also occurred in human intestinal cells (Caco-2). We found that the increase of NHE8 expression by somatostatin required p38 mitogen-activated protein kinase (MAPK) activation. Furthermore, the somatostatin receptor SSTR2 antagonist CYN154806 could abolish somatostatin-induced NHE8 expression and p38 MAPK phosphorylation. Thus our data provided the first concrete evidence indicating that somatostatin stimulates intestinal Na+ absorption by increasing intestinal NHE8 expression through the SSTR2-p38 MAPK pathway.

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