Roles of insulin, guanosine 5′-[<i>γ</i>-thio]triphosphate and phorbol 12-myristate 13-acetate in signalling pathways of GLUT4 translocation

Todaka, Mikio; Hayashi, Hideki; Imanaka, Toshinobu; Mitani, Yuichiro; Kamohara, Seika; Kishi, Kazuhiro; Tamaoka, Keisuke; Kanai, Fumihiko; Shichiri, Motoaki; Morii, Narito; Narumiya, Shuh; Ebina, Yasuhiko

doi:10.1042/bj3150875

Cited by 26 publications

(19 citation statements)

References 62 publications

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“…The inability of GDP␤S to prevent insulin-stimulated GLUT4 translocation at supraphysiological insulin concentrations has been previously reported, but the effect of GDP␤S was not examined at physiological insulin levels (49). There are several plausible reasons accounting for the ineffectiveness of GDP␤S at high insulin concentrations, including the possibility that insulin can mediate GLUT4 translocation by more than one signaling pathway, i.e.…”

Section: Discussionmentioning

confidence: 99%

Guanosine 5′-O-(3-Thiotriphosphate) (GTPγS) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent

Elmendorf

Chen

Pessin

1998

Journal of Biological Chemistry

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Guanosine 5-O-(3-thiotriphosphate) (GTP␥S) treatment of permeabilized adipocytes results in GLUT4 translocation similar to that elicited by insulin treatment. However, although the selective phosphatidylinositol 3-kinase inhibitor, wortmannin, completely prevented insulin-stimulated GLUT4 translocation, it was without effect on GTP␥S-stimulated GLUT4 translocation. In addition, insulin was an effective stimulant, whereas GTP␥S was a very weak activator of the downstream Akt serine/threonine kinase. Consistent with an Akt-independent mechanism, guanosine 5-O-2-(thio) diphosphate inhibited insulin-stimulated GLUT4 translocation without any effect on the Akt kinase. Surprisingly, two functionally distinct tyrosine kinase inhibitors, genistein and herbimycin A, as well as microinjection of a monoclonal phosphotyrosine specific antibody, inhibited both GTP␥S-and insulin-stimulated GLUT4 translocation. Phosphotyrosine immunoblotting and specific immunoprecipitation demonstrated that GTP␥S did not elicit tyrosine phosphorylation of insulin receptor or insulin receptor substrate-1. In contrast to insulin, proteins in the 120 -130-kDa and 55-75-kDa range were tyrosine-phosphorylated following GTP␥S stimulation. Several of these proteins were identified and include protein-tyrosine kinase 2 (also known as CAK␤, RAFTK, and CADTK), pp125 focal adhesion tyrosine kinase, pp130 Crk-associated substrate, paxillin, and Cbl. These data demonstrate that the GTP␥S-stimulated GLUT4 translocation utilizes a novel tyrosine kinase pathway that is independent of both the phosphatidylinositol 3-kinase and the Akt kinase.

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Section: Discussionmentioning

confidence: 99%

Guanosine 5′-O-(3-Thiotriphosphate) (GTPγS) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent

Elmendorf

Chen

Pessin

1998

Journal of Biological Chemistry

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“…29 The PKC activator PMA was shown to induce GLUT-4 translocation as well as an increased 3-O-methylglucose transport in adipocytes. 30,31 Conversely, in skeletal muscle cells PMA does not translocate GLUT-4 while increasing glucose uptake. 16 To our knowledge, there is no information concerning the effect of PKC activation on GLUT-4 in the heart.…”

Section: Discussionmentioning

confidence: 99%

Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester

et al. 2002

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OBJECTIVE:To investigate the influence of obesity on the regulation of myocardial glucose metabolism following protein kinase C (PKC) activation in obese (fa=fa) and lean (Fa=?) Zucker rats. DESIGN: Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) for different time periods prior to the evaluation of PKC and GLUT-4 translocation. For metabolic studies isolated hearts from 48 h starved Zucker rats were perfused with an erythrocytes-enriched buffer containing increased concentrations (10 -100 nM) of PMA. MEASUREMENTS: Immunodetectable PKC isozymes and GLUT-4 were determined by Western blots. Glucose oxidation and glycolysis were evaluated by measuring the myocardial release of 14 CO 2 and 3 H 2 O from [U-14 C]glucose and [5-3 H]glucose, respectively. RESULTS: PMA (200 nM) induced maximal translocation of ventricular PKCa from the cytosol to the membranes within 10 min. This translocation was 2-fold lower in the heart from obese rats when compared to lean rats. PMA also induced a significant translocation of ventricular GLUT-4 from the microsomal to the sarcolemmal fraction within 60 min in lean but not in obese rats. Rates of basal cardiac glucose oxidation and glycolysis in obese rats were approximately 2-fold lower than those of lean rats. Perfusion with increasing concentrations of PMA (10 -100 nM) led to a significant decrease of cardiac glucose oxidation in lean but not in obese rats. CONCLUSION: Our results show that in the heart of the genetically obese Zucker rat, the impairment in PKCa activation is in line with a diminished activation of GLUT-4 as well as with the lack of PMA effect on glucose oxidation.

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“…PI 3-Kinase Assay-Preparation of cell lysates and PI 3-kinase assay were done as described (24). Briefly, total cell lysates were prepared with buffer containing 1% Nonidet P-40 after treatment with the indicated concentrations of insulin or PDGF and precipitated with the PY20 antibodies and protein A-Sepharose CL-4B (Amersham Pharmacia Biotech).…”

Section: Fig 1 Effect Of Pdgf and Insulin On Glucose Uptake In 3t3-mentioning

confidence: 99%

Transient Effect of Platelet-derived Growth Factor on GLUT4 Translocation in 3T3-L1 Adipocytes

Wang

Hayashi

Ebina

1999

Journal of Biological Chemistry

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We earlier developed a novel method to detect translocation of the glucose transporter (GLUT) directly and simply using c-MYC epitope-tagged GLUT (GLUTMYC). To define the effect of platelet-derived growth factor (PDGF) on glucose transport in 3T3-L1 adipocytes, we investigated the PDGF-and insulin-induced glucose uptake, translocation of glucose transporters, and phosphatidylinositol (PI) 3-kinase activity in 3T3-L1, 3T3-L1GLUT4MYC, and 3T3-L1GLUT1MYC adipocytes. Insulin and PDGF stimulated glucose uptake by 9 -10-and 5.5-6.5-fold, respectively, in both 3T3-L1 and 3T3-L1GLUT4MYC adipocytes. Exogenous GLUT4MYC expression led to enhanced PDGF-induced glucose transport. In 3T3-L1GLUT4MYC adipocytes, insulin and PDGF induced an 8-and 5-fold increase in GLUT4MYC translocation, respectively, determined in a cell-surface anti-c-MYC antibody binding assay. This PDGF-induced GLUT4MYC translocation was further demonstrated with fluorescent detection. In contrast, PDGF stimulated a 2-fold increase of GLUT1MYC translocation and 2.5-fold increase of glucose uptake in 3T3-L1GLUT1MYC adipocytes. The PDGF-induced GLUT4MYC translocation, glucose uptake, and PI 3-kinase activity were maximal (100%) at 5-10 min and thereafter rapidly declined to 40, 30, and 12%, respectively, within 60 min, a time when effects of insulin were maximal. Wortmannin (0.1 M) abolished PDGF-induced GLUT4MYC translocation and glucose uptake in 3T3-L1GLUT4MYC adipocytes. These results suggest that PDGF can transiently trigger the translocation of GLUT4 and stimulate glucose uptake by translocation of both GLUT4 and GLUT1 in a PI 3-kinase-dependent signaling pathway in 3T3-L1 adipocytes.The insulin signaling pathway mediating the glucose transport is not fully understood. Translocation of GLUT4 1 from an intracellular pool to the plasma membrane is thought to be a major mechanism of glucose uptake in response to insulin in insulin-sensitive tissues (1-3). We (4) and others (5-8) found that PI 3-kinase activation is essential for insulin-stimulated glucose uptake. Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) activate many of the same signaling cascades as does insulin. One of the most prominent shared pathways is phosphatidylinositol 3-kinase. Therefore, the question arose as to whether PDGF or EGF would trigger GLUT4 translocation by the activation of PI 3-kinase. We developed a sensitive immunological method that can detect c-MYC epitope-tagged GLUT4 (GLUT4MYC) on the cell surface, directly and quantitatively (9). By using this method, we have found that PDGF and EGF did trigger the GLUT4 translocation to the plasma membrane in CHO and 3T3-L1 adipocytes by a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase, p85/p110 heterodimer type) (10, 11). We considered that PDGF and EGF as well as insulin may have latent potential to trigger GLUT4 translocation by activation of PI 3-kinase in cultured cells. PDGF-or EGF-triggered GLUT4 translocation has been reported by other research groups (12, 13). However, there is...

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Roles of insulin, guanosine 5′-[γ-thio]triphosphate and phorbol 12-myristate 13-acetate in signalling pathways of GLUT4 translocation

Cited by 26 publications

References 62 publications

Guanosine 5′-O-(3-Thiotriphosphate) (GTPγS) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent

Guanosine 5′-O-(3-Thiotriphosphate) (GTPγS) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent

Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester

Transient Effect of Platelet-derived Growth Factor on GLUT4 Translocation in 3T3-L1 Adipocytes

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