scholarly journals Affinity change of the adipocyte receptor fails to alter insulin-stimulated glucose transport

1982 ◽  
Vol 202 (1) ◽  
pp. 263-265 ◽  
Author(s):  
Michael L. McCaleb ◽  
David B. Donner
Keyword(s):  
Insulin Receptor ◽  
Glucose Transport ◽  
Maximum Response ◽  
Simple Relationship ◽  
Insulin Stimulation ◽  
Receptor Affinity ◽  
Maximal Sensitivity ◽  
Affinity Change ◽  
Stimulation Of

Occupancy increased the affinity of the insulin receptor of the adipocyte. During the affinity change the half-maximal sensitivity of glucose transport to insulin stimulation was unaltered. Decreased maximum response of transport only occurred after the affinity change. There was not a simple relationship between receptor affinity and insulin stimulation of glucose transport in the adipocyte.

scholarly journals Osmotic Shock Inhibits Insulin Signaling by Maintaining Akt/Protein Kinase B in an Inactive Dephosphorylated State

1999 ◽  
Vol 19 (7) ◽  
pp. 4684-4694 ◽  
Author(s):  
Dong Chen ◽  
Raymond V. Fucini ◽  
Ann Louise Olson ◽  
Brian A. Hemmings ◽  
Jeffrey E. Pessin
Keyword(s):  
Protein Kinase ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Protein Kinase B ◽  
Osmotic Shock ◽  
Glycogen Synthesis ◽  
Type I ◽  
Transport Activity ◽  
Insulin Stimulation ◽  
Stimulation Of

ABSTRACT We have previously reported that insulin and osmotic shock stimulate an increase in glucose transport activity and translocation of the insulin-responsive glucose transporter isoform GLUT4 to the plasma membrane through distinct pathways in 3T3L1 adipocytes (D. Chen, J. S. Elmendorf, A. L. Olson, X. Li, H. S. Earp, and J. E. Pessin, J. Biol. Chem. 272:27401–27410, 1997). In investigations of the relationships between these two signaling pathways, we have now observed that these two stimuli are not additive, and, in fact, osmotic shock pretreatment was found to completely prevent any further insulin stimulation of glucose transport activity and GLUT4 protein translocation. In addition, osmotic shock inhibited the insulin stimulation of lipogenesis and glycogen synthesis. This inhibition of insulin-stimulated downstream signaling occurred without any significant effect on insulin receptor autophosphorylation or tyrosine phosphorylation of insulin receptor substrate 1 (IRS1). Furthermore, there was no effect on either the insulin-stimulated association of the p85 type I phosphatidylinositol (PI) 3-kinase regulatory subunit with IRS1 or phosphotyrosine antibody-immunoprecipitated PI 3-kinase activity. In contrast, osmotic shock pretreatment markedly inhibited the insulin stimulation of protein kinase B (PKB) and p70S6 kinase activities. In addition, the dephosphorylation of PKB was prevented by pretreatment with the phosphatase inhibitors okadaic acid and calyculin A. These data support a model in which osmotic shock-induced insulin resistance of downstream biological responses results from an inhibition of insulin-stimulated PKB activation.

Glucosamine-induced insulin resistance in 3T3-L1 adipocytes

2000 ◽  
Vol 278 (1) ◽  
pp. E103-E112 ◽  
Author(s):  
Emma Heart ◽  
Woo S. Choi ◽  
Chin K. Sung
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Insulin Stimulation ◽  
Glut 4 ◽  
Impaired Insulin ◽  
Glut 4 Translocation ◽  
Stimulation Of

To study molecular mechanisms for glucosamine-induced insulin resistance, we induced complete and reversible insulin resistance in 3T3-L1 adipocytes with glucosamine in a dose- and time-dependent manner (maximal effects at 50 mM glucosamine after 6 h). In these cells, glucosamine impaired insulin-stimulated GLUT-4 translocation. Glucosamine (6 h) did not affect insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 and -2 and weakly, if at all, impaired insulin stimulation of phosphatidylinositol 3-kinase. Glucosamine, however, severely impaired insulin stimulation of Akt. Inhibition of insulin-stimulated glucose transport was correlated with that of Akt activity. In these cells, glucosamine also inhibited insulin stimulation of p70 S6 kinase. Glucosamine did not alter basal glucose transport and insulin stimulation of GLUT-1 translocation and mitogen-activated protein kinase. In summary, glucosamine induced complete and reversible insulin resistance in 3T3-L1 adipocytes. This insulin resistance was accompanied by impaired insulin stimulation of GLUT-4 translocation and Akt activity, without significant impairment of upstream molecules in insulin-signaling pathway.

Insulin stimulation of glucose transport in adipose cells. An energy-dependent process

Biochemistry ◽  
1977 ◽  
Vol 16 (6) ◽  
pp. 1151-1158 ◽  
Author(s):  
Visvanathan Chandramouli ◽  
Marianne Milligan ◽  
James R. Carter
Keyword(s):  
Glucose Transport ◽  
Insulin Stimulation ◽  
Dependent Process ◽  
Energy Dependent ◽  
Adipose Cells ◽  
Stimulation Of

scholarly journals Effects of ML-9 on insulin stimulation of glucose transport in 3T3-L1 adipocytes.

1993 ◽  
Vol 268 (7) ◽  
pp. 5272-5278 ◽  
Author(s):  
G. Inoue ◽  
H. Kuzuya ◽  
T. Hayashi ◽  
M. Okamoto ◽  
Y. Yoshimasa ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Insulin Stimulation ◽  
Stimulation Of

scholarly journals Insulin receptor substrate 1 rescues insulin action in CHO cells expressing mutant insulin receptors that lack a juxtamembrane NPXY motif.

1995 ◽  
Vol 15 (9) ◽  
pp. 4711-4717 ◽  
Author(s):  
D Chen ◽  
D J Van Horn ◽  
M F White ◽  
J M Backer
Keyword(s):  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Cho Cells ◽  
Glycogen Synthesis ◽  
Insulin Receptors ◽  
Insulin Receptor Substrate ◽  
Insulin Stimulation ◽  
Insulin Receptor Substrate 1 ◽  
Npxy Motif ◽  
Stimulation Of

Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 (IRS-1) and Shc by the activated insulin receptor (IR). Phosphorylation of both proteins is nearly abolished by an alanine substitution at Tyr-960 (A960) in the beta-subunit of the receptor. However, overexpression of IRS-1 in CHO cells expressing the mutant receptor (A960 cells) restored sufficient tyrosine phosphorylation of IRS-1 to rescue IRS-1/Grb-2 binding and phosphatidylinositol 3' kinase activation during insulin stimulation. Shc tyrosine phosphorylation and its binding to Grb-2 were impaired in the A960 cells and were unaffected by overexpression of IRS-1. Although overexpression of IRS-1 increased IRS-1 binding to Grb-2, ERK-1/ERK-2 activation was not rescued. These data suggest that signaling molecules other than IRS-1, perhaps including Shc, are critical for insulin stimulation of p21ras. Interestingly, overexpression of IRS-1 in the A960 cells restored insulin-stimulated mitogenesis and partially restored insulin stimulation of glycogen synthesis. Thus, IRS-1 tyrosine phosphorylation is sufficient to increase the mitogenic response to insulin, whereas insulin stimulation of glycogen synthesis appears to involve other factors. Moreover, IRS-1 phosphorylation is either not sufficient or not involved in insulin stimulation of ERK.

Role of IRS-1-GRB-2 complexes in insulin signaling

1994 ◽  
Vol 14 (6) ◽  
pp. 3577-3587
Author(s):  
M G Myers ◽  
L M Wang ◽  
X J Sun ◽  
Y Zhang ◽  
L Yenush ◽  
...  
Keyword(s):  
Map Kinase ◽  
Insulin Receptor ◽  
Insulin Receptors ◽  
Growth Factor Signaling ◽  
Insulin Stimulation ◽  
Mitogen Activated Protein ◽  
D Cells ◽  
Stimulation Of

GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21ras during growth factor signaling. During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1. Substitution of Tyr-895 with phenylalanine (IRS-1F-895) prevented the IRS-1-GRB-2 association in vivo and in vitro. The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase. The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells. Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. Our results suggest that the Shc-GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation.

Insulin-stimulated cytosol alkalinization facilitates optimal activation of glucose transport in cardiomyocytes

2002 ◽  
Vol 283 (6) ◽  
pp. E1299-E1307 ◽  
Author(s):  
Jing Yang ◽  
Alison K. Gillingham ◽  
Alois Hodel ◽  
Françoise Koumanov ◽  
Brian Woodward ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Glucose Transport ◽  
Insulin Treatment ◽  
Ph Regulation ◽  
Bafilomycin A1 ◽  
Transport Activity ◽  
Insulin Stimulation ◽  
Cytosolic Ph ◽  
Syntaxin 4

Abnormalities in intracellular pH regulation have been proposed to be important in type 2 diabetes and the associated cardiomyopathy and hypertension. We have therefore investigated the dependence of insulin-stimulated glucose transport on cytosolic pH in cardiomyocytes. Insulin treatment of cardiomyocytes resulted in a marked alkalinization of the cytoplasm as measured using carboxy-semi-napthorhodofluor-1. The alkalinizing effect of insulin was blocked by treatment with either cariporide (which inhibits the Na+/H+ exchanger) or by bafilomycin A1 (which inhibits H+-ATPase activity). After treatments with cariporide or bafilomycin A1, insulin stimulation of insulin receptor and insulin receptor substrate-1 phosphorylation and Akt activity were normal. In contrast, glucose transport activity and the levels of functional GLUT4 at the plasma membrane (detected using an exofacial photolabel) were reduced by ∼50%. Immunocytochemical analysis revealed that insulin treatment caused a translocation of the GLUT4 from perinuclear structures and increased its co-localization with cell surface syntaxin 4. However, neither cariporide nor bafilomycin A1 treatment reduced the translocation of immunodetectable GLUT4 to the sarcolemma region of the cell. It is therefore hypothesized that insulin-stimulated cytosol alkalinization facilitates the final stages of translocation and incorporation of fully functional GLUT4 at the surface-limiting membrane.

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