Cellular mechanism of the insulin-like effect of growth hormone in adipocytes. Rapid translocation of the HepG2-type and adipocyte/muscle glucose transporters

Tanner, Jean-Paul; Leingang, Karen A.; Mueckler, Mike; Glenn, Kevin C.

doi:10.1042/bj2820099

Cited by 28 publications

(14 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GH effects on glucose transport were recently shown to be due to direct recruitment of the transporters GLUT1 and GLUT4 to the plasma membrane (49). As GLUT1 is the only recruitable transporter present in blastocysts (50,51), it follows that the increase in glucose transport observed in our study is due to direct GH stimulation of GLUT1 recruitment͞synthesis.…”

Section: Discussionsupporting

confidence: 54%

Functional growth hormone (GH) receptors and GH are expressed by preimplantation mouse embryos: A role for GH in early embryogenesis?

Pantaleon

Whiteside

Harvey

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

The results of this study challenge the widely held view that growth hormone (GH) acts only during the postnatal period. RNA phenotyping shows transcripts for the GH receptor and GH-binding protein in mouse preimplantation embryos of all stages from fertilized eggs (day 1) to blastocysts (day 4). An antibody specific to the cytoplasmic region of the GH receptor revealed receptor protein expression, first in two-cell embryos, the stage of activation of the embryonic genome (day 2), and in all subsequent stages. In cleavage-stage embryos this immunoreactivity was localized mainly to the nucleus, but clear evidence of membrane labeling was apparent in blastocysts. GH receptor immunoreactivity was also observed in cumulus cells associated with unfertilized oocytes but not in the unfertilized oocytes. The blastocyst receptor was demonstrated to be functional, exhibiting the classic bell-shaped dose-response curves for GH stimulation of both 3-O-methyl glucose transport and protein synthesis. Maximal stimulation of 40-50% was seen for both responses at less than 1 ng͞ml recombinant GH, suggesting a role for maternal GH. However mRNA transcripts for GH were also detected from the morula stage (day 3) by using reverse transcription-PCR, and GH immunoreactivity was seen in blastocysts. These observations raise the possibility of a paracrine͞autocrine GH loop regulating embryonic development in its earliest stages.Embryonic and fetal growth have long been considered to be independent of pituitary growth hormone (GH). However, this view is challenged by a growing body of evidence which demonstrates a role for GH in the development of the fetus. Newborn Laron dwarfs, lacking a functional GH receptor, are more than 2 SD shorter than normal (1). Exogenous GH has been shown to restore embryonic growth in rats after transplantation of parts of embryos into hypophysectomized hosts (2). A number of fetal tissues has been shown to respond to GH in vitro (3-6). GH receptor transcripts have been demonstrated in day 12 rat embryos and placentae (7), day 51 sheep embryos (8), and mouse placenta (9). Immunoreactive GH receptor was observed in the human fetus from the second trimester (10, 11). Recently GH receptor transcripts and immunoreactivity have been demonstrated in germ-line competent mouse embryonic stem cells, and GH receptor transcripts were also demonstrated in mouse blastocysts (12).Preimplantation stages earlier than the blastocyst, however, were not examined by Ohlsson et al. (12). Furthermore, there was no evidence that these very early embryos were capable of receptor synthesis or of signal transduction after ligand binding to expressed receptor. In this study we demonstrate the presence of GH receptors in the early embryo from fertilization to the blastocyst stage and the ability of GH to influence the metabolism of blastocyst. Moreover, we report the expression of GH by preimplantation blastocysts, raising the possibility of paracrine͞autocrine regulation of embryonic growth by GH. MATERIALS AND METHODSGene Ex...

show abstract

Section: Discussionsupporting

confidence: 54%

Functional growth hormone (GH) receptors and GH are expressed by preimplantation mouse embryos: A role for GH in early embryogenesis?

Pantaleon

Whiteside

Harvey

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

show abstract

“…Adipogenic induction of PLA cells also resulted in lineage-specific gene and protein expression. Immunofluores- cence confirmed the expression of leptin and GLUT4 in induced PLA samples ( Figure 2B), two proteins that are up-regulated in differentiating adipocytes (Tanner et al, 1992;Chen et al, 1997). Expression of these proteins seemed to be restricted to mature, lipid-filled PLA cells, as low levels were observed in cells with a fibroblastic morphology.…”

Section: Pla Cells Undergo Adipogenic Differentiation In Vitromentioning

confidence: 65%

Human Adipose Tissue Is a Source of Multipotent Stem Cells

Zuk

Zhu

Ashjian

et al. 2002

MBoC

5,925

144

4,535

View full text Add to dashboard Cite

Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

show abstract

“…We then determined PI 3-kinase activity in the anti-IRS-1 antibody immunoprecipitates. Chronic GH treatment alone increased IRS-1-associated PI 3-kinase activity 1.7-fold, and GH significantly enhanced insulinstimulated PI 3-kianse activity by 45,39, and 25% at insulin concentrations of 0.2, 2.0, and 20 nmol/l, respectively (Fig. 5A).…”

Section: Resultsmentioning

confidence: 99%

“…The activated JAK2 mediates tyrosine phosphorylation of various signaling molecules, including Shc, signal transducers and activators of transcription (STAT), IRS-1, and IRS-2 (36 -44). Tyrosine phosphorylation of IRS-1 by JAK2 is likely to mediate some insulin-like effects elicited by short-term GH stimulation (36,(45)(46)(47). However, it is not clear whether chronic GH treatment directly induces insulin resistance in insulin target cells, and the molecular mechanism of GH-induced insulin resistance has not been clarified.…”

mentioning

confidence: 99%

Growth Hormone Induces Cellular Insulin Resistance by Uncoupling Phosphatidylinositol 3-Kinase and Its Downstream Signals in 3T3-L1 Adipocytes

et al. 2001

View full text Add to dashboard Cite

Growth hormone (GH) is well known to induce in vivo insulin resistance. However, the molecular mechanism of GH-induced cellular insulin resistance is largely unknown. In this study, we demonstrated that chronic GH treatment of differentiated 3T3-L1 adipocytes reduces insulin-stimulated 2-deoxyglucose (DOG) uptake and activation of Akt (also known as protein kinase B), both of which are downstream effects of phosphatidylinositol (PI) 3-kinase, despite enhanced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, association of IRS-1 with the p85 subunit of PI 3-kinase, and IRS-1-associated PI 3-kinase activity. In contrast, chronic GH treatment did not affect 2-DOG uptake and Akt activation induced by overexpression of a membrane-targeted form of the p110 subunit of PI 3-kinase (p110 CAAX ) or Akt activation stimulated by plateletderived growth factor. Fractionation studies indicated that chronic GH treatment reduces insulin-stimulated translocation of Akt from the cytosol to the plasma membrane. Interestingly, chronic GH treatment increased insulin-stimulated association of IRS-1 with p85 and IRS-1-associated PI 3-kinase activity preferentially in the cytosol. These results indicate that cellular insulin resistance induced by chronic GH treatment in 3T3-L1 adipocytes is caused by uncoupling between activation of PI 3-kinase and its downstream signals, which is specific to the insulin-stimulated PI 3-kinase pathway. This effect of GH might result from the altered subcellular distribution of IRS-1-associated PI 3-kinase.

show abstract

Cellular mechanism of the insulin-like effect of growth hormone in adipocytes. Rapid translocation of the HepG2-type and adipocyte/muscle glucose transporters

Cited by 28 publications

References 49 publications

Functional growth hormone (GH) receptors and GH are expressed by preimplantation mouse embryos: A role for GH in early embryogenesis?

Functional growth hormone (GH) receptors and GH are expressed by preimplantation mouse embryos: A role for GH in early embryogenesis?

Human Adipose Tissue Is a Source of Multipotent Stem Cells

Growth Hormone Induces Cellular Insulin Resistance by Uncoupling Phosphatidylinositol 3-Kinase and Its Downstream Signals in 3T3-L1 Adipocytes

Contact Info

Product

Resources

About