scholarly journals 5-Aminoimidazole-4-carboxamide riboside (AICAR) enhances GLUT2-dependent jejunal glucose transport: a possible role for AMPK

2005 ◽  
Vol 385 (2) ◽  
pp. 485-491 ◽  
Author(s):  
John WALKER ◽  
Humberto B. JIJON ◽  
Hugo DIAZ ◽  
Payam SALEHI ◽  
Thomas CHURCHILL ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Western Blotting ◽  
Glucose Transporter ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Energy Status ◽  
P38 Inhibitor ◽  
Mitogen Activated Protein

AMPK (AMP-activated protein kinase) is a key sensor of energy status within the cell. Activated by an increase in the AMP/ATP ratio, AMPK acts to limit cellular energy depletion by down-regulating selective ATP-dependent processes. The purpose of the present study was to determine the role of AMPK in regulating intestinal glucose transport. [3H]3-O-methyl glucose fluxes were measured in murine jejunum in the presence and absence of the AMPK activators AICAR (5-aminoimidazole-4-carboxamide riboside) and metformin and the p38 inhibitor, SB203580. To differentiate between a sodium-coupled (SGLT1) and diffusive (GLUT2) route of entry, fluxes were measured in the presence of the SGLT1 and GLUT2 inhibitors phloridzin and phloretin. Glucose transporter mRNA levels were measured by reverse transcriptase–PCR, and localization by Western blotting. Surface-expressed GLUT2 was assessed by luminal biotinylation. Activation of p38 mitogen-activated protein kinase was analysed by Western blotting. We found that treatment of jejunal tissue with AICAR resulted in enhanced net glucose uptake and was associated with phosphorylation of p38 mitogen-activated protein kinase. Inhibition of p38 abrogated the stimulation of AICAR-stimulated glucose uptake. Phloretin abolished the AICAR-mediated increase in glucose flux, whereas phloridzin had no effect, suggesting the involvement of GLUT2. In addition, AICAR decreased total protein levels of SGLT1, concurrently increasing levels of GLUT2 in the brush-border membrane. The anti-diabetic drug metformin, a known activator of AMPK, also induced the localization of GLUT2 to the luminal surface. We conclude that the activation of AMPK results in an up-regulation of non-energy requiring glucose uptake by GLUT2 and a concurrent down-regulation of sodium-dependent glucose transport.

scholarly journals Exercise signalling to glucose transport in skeletal muscle

2004 ◽  
Vol 63 (2) ◽  
pp. 211-216 ◽  
Author(s):  
Erik A. Richter ◽  
Jakob N. Nielsen ◽  
Sebastian B. Jørgensen ◽  
Christian Frøsig ◽  
Jesper B. Birk ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Surface Membrane ◽  
Mitogen Activated Protein Kinase ◽  
Storage Site ◽  
Mitogen Activated Protein ◽  
Intracellular Storage

Contraction-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism that leads to translocation of the GLUT4 glucose transporter to the muscle surface membrane from an intracellular storage site. Although the signalling events that increase glucose transport in response to muscle contraction are not fully elucidated, the aim of the present review is to briefly present the current understanding of the molecular signalling mechanisms involved. Glucose uptake may be regulated by Ca2+-sensitive contraction-related mechanisms, possibly involving Ca2+/calmodulin-dependent protein kinase II and some isoforms of protein kinase C. In addition, glucose transport may be regulated by mechanisms that reflect the metabolic status of the muscle, probably involving the 5′AMP-activated protein kinase. Furthermore, the p38 mitogen-activated protein kinase may be involved in activating the GLUT4 translocated to the surface membrane. Nevertheless, the picture is incomplete, and fibre type differences also seem to be involved.

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 acts via mitogen-activated protein kinase phosphorylation in rabbit blastocysts

Reproduction ◽  
2004 ◽  
Vol 128 (5) ◽  
pp. 517-526 ◽  
Author(s):  
Anne Navarrete Santos ◽  
Sarah Tonack ◽  
Michaela Kirstein ◽  
Marie Pantaleon ◽  
Peter Kaye ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Transport ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Preimplantation Embryos ◽  
Mrna Levels ◽  
Glut4 Translocation ◽  
Mitogen Activated Protein ◽  
Rabbit Embryos

The addition of insulin during in vitro culture has beneficial effects on rabbit preimplantation embryos leading to increased cell proliferation and reduced apoptosis. We have previously described the expression of the insulin receptor (IR) and the insulin-responsive glucose transporters (GLUT) 4 and 8 in rabbit preimplantation embryos. However, the effects of insulin on IR signaling and glucose metabolism have not been investigated in rabbit embryos. In the present study, the effects of 170 nM insulin on IR, GLUT4 and GLUT8 mRNA levels, Akt and Erk phosphorylation, GLUT4 translocation and methyl glucose transport were studied in cultured day 3 to day 6 rabbit embryos. Insulin stimulated phosphorylation of the mitogen-activated protein kinase (MAPK) Erk1/2 and levels of IR and GLUT4 mRNA, but not phosphorylation of the phosphatidylinositol 3-kinase-dependent protein kinase, Akt, GLUT8 mRNA levels, glucose uptake or GLUT4 translocation. Activation of the MAPK signaling pathway in the absence of GLUT4 translocation and of a glucose transport response suggest that in the rabbit preimplantation embryo insulin is acting as a growth factor rather than a component of glucose homeostatic control.

scholarly journals Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 711-719 ◽  
Author(s):  
Munkhuu Bayarsaikhan ◽  
Akiko Shiratsuchi ◽  
Davaakhuu Gantulga ◽  
Yoshinobu Nakanishi ◽  
Katsuji Yoshioka
Keyword(s):  
Protein Kinase ◽  
Western Blotting ◽  
Cell Types ◽  
Mapk Signaling ◽  
Scaffold Protein ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Early Postnatal Development ◽  
Mitogen Activated Protein ◽  
Signaling Modules

Scaffold proteins of mitogen-activated protein kinase (MAPK) intracellular signal transduction pathways mediate the efficient and specific activation of the relevant MAPK signaling modules. Previously, our group and others have identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffold protein for JNK MAPK pathways. Although JSAP1 is expressed in the testis in adults, its expression during development has not been investigated. In addition, it is unknown which types of cells in the testis express the scaffold protein. Here, we examined the expression of JSAP1 in the testis of mice aged 14 days, 20 days, 6 weeks, and 12 weeks by immunohistochemistry and Western blotting. The specificity of the anti-JSAP1 antibody was evaluated from its reactivity to exogenously expressed JSAP1 and a structurally related protein, and by antigen-absorption experiments. The immunohistochemical analyses with the specific antibody showed that the JSAP1 protein was selectively expressed in the spermatogonia and spermatocytes, but not in other cell types, including spermatids and somatic cells, during development. However, not all spermatogonia and spermatocytes were immunopositive either, especially in the 12-week-old mouse testis. Furthermore, we found by Western blotting that the expression levels of JSAP1 protein vary during development; there is high expression until 6 weeks after birth, which approximately corresponds to the end of the first wave of spermatogenesis. Collectively, these results suggest that JSAP1 function may be important in spermatogenic cells during early postnatal development.

scholarly journals Helicobacter pylori VacA Enhances Prostaglandin E2 Production through Induction of Cyclooxygenase 2 Expression via a p38 Mitogen-Activated Protein Kinase/Activating Transcription Factor 2 Cascade in AZ-521 Cells

2007 ◽  
Vol 75 (9) ◽  
pp. 4472-4481 ◽  
Author(s):  
Junzo Hisatsune ◽  
Eiki Yamasaki ◽  
Masaaki Nakayama ◽  
Daisuke Shirasaka ◽  
Hisao Kurazono ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Transcription Factor ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Cyclooxygenase 2 ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Mitogen Activated Protein ◽  
Cox 2 ◽  
Activating Transcription Factor

ABSTRACT Treatment of AZ-521 cells with Helicobacter pylori VacA increased cyclooxygenase 2 (COX-2) mRNA in a time- and dose-dependent manner. A p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, blocked elevation of COX-2 mRNA levels, whereas PD98059, which blocks the Erk1/2 cascade, partially suppressed the increase. Consistent with involvement of p38 MAPK, VacA-induced accumulation of COX-2 mRNA was reduced in AZ-521 cells overexpressing a dominant-negative p38 MAPK (DN-p38). Phosphatidylinositol-specific phospholipase C, which inhibits VacA-induced p38 MAPK activation, blocked VacA-induced COX-2 expression. In parallel with COX-2 expression, VacA increased prostaglandin E2 (PGE2) production, which was inhibited by SB203580 and NS-398, a COX-2 inhibitor. VacA-induced PGE2 production was markedly attenuated in AZ-521 cells stably expressing DN-p38. VacA increased transcription of a COX-2 promoter reporter gene and activated a COX-2 promoter containing mutated NF-κB or NF-interleukin-6 sites but not a mutated cis-acting replication element (CRE) site, suggesting direct involvement of the activating transcription factor 2 (ATF-2)/CREB-binding region in VacA-induced COX-2 promoter activation. The reduction of ATF-2 expression in AZ-521 cells transformed with ATF-2-small interfering RNA duplexes resulted in suppression of COX-2 expression. Thus, VacA enhances PGE2 production by AZ-521 cells through induction of COX-2 expression via the p38 MAPK/ATF-2 cascade, leading to activation of the CRE site in the COX-2 promoter.

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