scholarly journals Role of guanine nucleotide regulatory proteins in insulin stimulation of glucose transport in rat adipocytes. Influence of bacterial toxins

1989 ◽  
Vol 264 (2) ◽  
pp. 389-396 ◽  
Author(s):  
T P Ciaraldi ◽  
A Maisel
Keyword(s):  
Glucose Transport ◽  
Pertussis Toxin ◽  
Insulin Binding ◽  
Regulatory Proteins ◽  
Guanine Nucleotide ◽  
Insulin Stimulation ◽  
Guanine Nucleotide Regulatory Proteins ◽  
Toxin Inhibition ◽  
Stimulation Of

The potential role of guanine nucleotide regulatory proteins (G-proteins) in acute insulin regulation of glucose transport was investigated by using bacterial toxins which are known to modify these proteins. Cholera-toxin treatment of isolated rat adipocytes had no effect on either 2-deoxyglucose transport or insulin binding. Pertussis-toxin treatment resulted in an inhibition of both insulin binding and glucose transport. Insulin binding was decreased in pertussis-toxin-treated cells by up to 40%, owing to a lowering of the affinity of the receptor for hormone, with no change in hormone internalization. The dose-response curve for insulin stimulation of glucose transport was strongly shifted to the right by pertussis-toxin treatment [EC50 (half-maximally effective insulin concn.) = 0.31 +/- 0.04 ng/ml in control cells; 2.29 +/- 1.0 in treated cells), whereas cholera toxin had only a small effect (EC50 = 0.47 +/- 0.02 ng/ml). Correcting for the change in hormone binding, pertussis toxin was found to decrease the coupling efficiency of occupied receptors (50% of maximal insulin effect with 928 molecules bound/cell in control and 3418 in treated cells). Pertussis-toxin inhibition of insulin sensitivity was slow in onset, requiring 2-3 h for completion. Under conditions where pertussis-toxin inhibition of insulin sensitivity was maximal, a 41,000 Da protein similar to the alpha subunit of Gi (the inhibitory G-protein) was found to be fully ribosylated. These results are consistent with the concept that pertussis-toxin-sensitive G-protein(s) can modify the insulin-receptor/glucose-transport coupling system.

Thrombin-induced prostacyclin biosynthesis in human endothelium: Role of guanine nucleotide regulatory proteins in stimulus/coupling responses

1990 ◽  
Vol 142 (1) ◽  
pp. 186-193 ◽  
Author(s):  
Joe G. N. Garcia ◽  
Richard G. Painter ◽  
John W. Fenton ◽  
Denis English ◽  
Karleen S. Callahan
Keyword(s):  
Regulatory Proteins ◽  
Guanine Nucleotide ◽  
Guanine Nucleotide Regulatory Proteins ◽  
Human Endothelium

Role of kinases in insulin stimulation of glucose transport

1989 ◽  
Vol 111 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Amira Klip ◽  
Andre G. Douen
Keyword(s):  
Glucose Transport ◽  
Insulin Stimulation ◽  
Stimulation Of

Modulation of NO and endothelin by chronic increases in blood flow in canine femoral arteries

1992 ◽  
Vol 263 (1) ◽  
pp. H103-H108 ◽  
Author(s):  
V. M. Miller ◽  
J. C. Burnett
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Pertussis Toxin ◽  
Isometric Force ◽  
Regulatory Proteins ◽  
Arterial Blood Flow ◽  
Guanine Nucleotide ◽  
Femoral Arteries ◽  
Arterial Blood ◽  
Guanine Nucleotide Regulatory Proteins

Experiments were designed to determine whether chronic increases in arterial blood flow alter production of or response to nitric oxide and endothelin. Canine femoral arteries proximal to an arteriovenous fistula- and from the contralateral sham-operated blood vessels were removed, cut into rings, and suspended for measurement of isometric force in organ chambers. The remainder of the artery was homogenized for measurement of endothelin content by radioimmunoassay. NG-monomethyl-L-arginine (10(-4) M) caused concentration-dependent increases in tension only in fistula-operated arteries. Endothelium-dependent relaxations to acetylcholine and BHT-920 were greater in fistula- compared with sham-operated arteries. These differences were reduced by the arginine analogue. Pertussis toxin (100 ng/ml) inhibited relaxations to acetylcholine only in fistula-operated arteries and to BHT-920 only in sham-operated arteries. Contractions to endothelin-1 were greater in fistula- compared with sham-operated arteries. These results suggest that chronic increases in blood flow enhance the tonic and receptor-stimulated production of nitric oxide and its release by receptors coupled to pertussis toxin-sensitive guanine nucleotide regulatory proteins. Furthermore, chronic increases in blood flow may either inhibit the production of endothelin or promote its depletion from endothelial cells while simultaneously increasing the sensitivity of the smooth muscle to its contractile effects.

scholarly journals Catecholamine-induced insulin resistance of glucose transport in isolated rat adipocytes

1983 ◽  
Vol 216 (3) ◽  
pp. 737-745 ◽  
Author(s):  
D M Kirsch ◽  
M Baumgarten ◽  
T Deufel ◽  
F Rinninger ◽  
W Kemmler ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Insulin Binding ◽  
Affinity Binding ◽  
Insulin Stimulation ◽  
High Affinity Binding ◽  
Rat Adipocytes ◽  
High Affinity ◽  
Atp Levels ◽  
Isolated Rat ◽  
Stimulation Of

The effects of pre-incubation with isoprenaline and noradrenaline on insulin binding and insulin stimulation of D-glucose transport in isolated rat adipocytes are reported. (1) Pre-incubation of the cells with isoprenaline (0.1-10 microM) in Krebs-Ringer-Hepes [4-(2-hydroxyethyl)-1-piperazine-ethanesulphonic acid] buffer (30 min, 37 degrees C) at D-glucose concentrations of 16 mM, in which normal ATP levels were maintained, caused a rightward-shift in sensitivity of D-glucose transport to insulin stimulation by 50% and a decrease in maximal responsiveness by 30% (2) [A14-125I]insulin binding was reduced significantly by 35% at insulin concentrations less than 100 mu-units/ml and Scatchard analysis showed that this consisted mainly of a decrease in high-affinity binding. (3) Pre-incubation with catecholamines under the same conditions but at low glucose concentrations (0-5 mM) caused a fall in intracellular ATP levels of 65 and 45% respectively. (4) The fall in ATP additionally lowered insulin binding by 50% at all insulin concentrations and a parallel shift of the binding curves in the Scatchard plot showed that this was due to a decrease in the number of receptors. (5) At low and high ATP concentrations the insulin stimulation of D-glucose transport was inhibited to a similar extent. (6) Pre-incubation with catecholamines thus inhibited insulin stimulation of D-glucose transport in rat adipocytes mainly by a decrease in high-affinity binding of insulin, which was not mediated by low ATP levels. This mechanism may play a role in the pathogenesis of catecholamine-induced insulin resistance in vivo.

scholarly journals Guanine nucleotide regulation of phospholipase C activity in permeabilized rabbit neutrophils. Inhibition by pertussis toxin and sensitization to submicromolar calcium concentrations

1986 ◽  
Vol 239 (1) ◽  
pp. 97-102 ◽  
Author(s):  
P G Bradford ◽  
R P Rubin
Keyword(s):  
Phospholipase C ◽  
G Protein ◽  
Pertussis Toxin ◽  
Response Curve ◽  
Regulatory Protein ◽  
Guanine Nucleotide ◽  
Nucleotide Regulation ◽  
Guanine Nucleotide Regulatory Protein ◽  
Stimulation Of

Rabbit neutrophils labelled with [3H]inositol and permeabilized with saponin produced [3H]inositol trisphosphate (InsP3) when incubated with stable analogues of GTP or millimolar concentrations of Ca2+. [3H]InsP3 production elicited by guanosine 5′-[gamma-thio]triphosphate was enhanced by the chemoattractant formylmethionyl-leucyl-phenylalanine and inhibited by pertussis-toxin pretreatment. A pertussis-toxin-sensitive stimulation of [3H]InsP3 concentration was also observed with guanosine 5′-[beta gamma-imido]triphosphate, but not with guanosine 5′-[beta-thio]diphosphate or GTP. Millimolar Ca2+ alone was sufficient to stimulate [3H]InsP3 production; however, in the presence of guanosine 5′-[gamma-thio]triphosphate, the Ca2+ dose-response curve was shifted to submicromolar concentrations. These findings directly confirm the role of a pertussis-toxin-sensitive guanine nucleotide regulatory protein (G protein) in chemoattractant-stimulated phospholipase C activity in rabbit neutrophils. Moreover, the ability of guanine nucleotides to sensitize phospholipase C to physiologically relevant Ca2+ concentrations suggests that the role of the activated G protein may be to enhance the apparent affinity of phospholipase C for Ca2+ and thus to activate the enzyme without an increase in the Ca2+ concentration.

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