Dissociation of insulin binding from insulin stimulation of 2-deoxyglucose transport by ruthenium red

1986 ◽  
Vol 6 (3) ◽  
pp. 317-322 ◽  
Author(s):  
P. F. Williams ◽  
W. E. Plehwe ◽  
J. R. Turtle
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Action ◽  
Insulin Binding ◽  
Ruthenium Red ◽  
Insulin Stimulation ◽  
Receptor Affinity ◽  
Enhancing Effect ◽  
Isolated Adipocytes ◽  
Specific Insulin ◽  
Stimulation Of

Ruthenium red increased specific insulin binding to isolated adipocytes 5.4 fold and 2.6 fold over binding determined in the absence and presence of Ca2+ and Mg2+. The increase in insulin binding was not accompanied by an increase in insulin sensitivity. The lack of effect of ruthenium red on insulin action argued strongly against an increase in intracellular Ca2+ as a potential messenger/transducer of insulin action and suggested that the enhancing effect of Ca2+ on insulin action was a result of increased receptor affinity.

Insulin action and cirrhosis: Insulin binding and lipogenesis in isolated adipocytes

Metabolism ◽  
1982 ◽  
Vol 31 (12) ◽  
pp. 1241-1246 ◽  
Author(s):  
M.S. Harewood ◽  
J. Proietto ◽  
F. Dudley ◽  
F.P. Alford
Keyword(s):  
Insulin Action ◽  
Insulin Binding ◽  
Isolated Adipocytes

scholarly journals Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

2015 ◽  
Vol 309 (4) ◽  
pp. E388-E397 ◽  
Author(s):  
Adam J. Trewin ◽  
Leonidas S. Lundell ◽  
Ben D. Perry ◽  
Kim Vikhe Patil ◽  
Alexander V. Chibalin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Repeated Measures ◽  
Insulin Action ◽  
Human Skeletal Muscle ◽  
Protein Signaling ◽  
Insulin Stimulation ◽  
Double Blind ◽  
Exercise Induced ◽  
Muscle Biopsies

—Reactive oxygen species (ROS) produced in skeletal muscle may play a role in potentiating the beneficial responses to exercise; however, the effects of exercise-induced ROS on insulin action and protein signaling in humans has not been fully elucidated. Seven healthy, recreationally active participants volunteered for this double-blind, randomized, repeated-measures crossover study. Exercise was undertaken with infusion of saline (CON) or the antioxidant N-acetylcysteine (NAC) to attenuate ROS. Participants performed two 1-h cycling exercise sessions 7–14 days apart, 55 min at 65% V̇o2peak plus 5 min at 85%V̇o2peak, followed 3 h later by a 2-h hyperinsulinemic euglycemic clamp (40 mIU·min−1·m2) to determine insulin sensitivity. Four muscle biopsies were taken on each trial day, at baseline before NAC infusion (BASE), after exercise (EX), after 3-h recovery (REC), and post-insulin clamp (PI). Exercise, ROS, and insulin action on protein phosphorylation were evaluated with immunoblotting. NAC tended to decrease postexercise markers of the ROS/protein carbonylation ratio by −13.5% ( P = 0.08) and increase the GSH/GSSG ratio twofold vs. CON ( P < 0.05). Insulin sensitivity was reduced (−5.9%, P < 0.05) by NAC compared with CON without decreased phosphorylation of Akt or AS160. Whereas p-mTOR was not significantly decreased by NAC after EX or REC, phosphorylation of the downstream protein synthesis target kinase p70S6K was blunted by 48% at PI with NAC compared with CON ( P < 0.05). We conclude that NAC infusion attenuated muscle ROS and postexercise insulin sensitivity independent of Akt signaling. ROS also played a role in normal p70S6K phosphorylation in response to insulin stimulation in human skeletal muscle.

scholarly journals Signalling pathways of an insulin-mimetic phosphoinositolglycan–peptide in muscle and adipose tissue

1998 ◽  
Vol 330 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Alexandra KESSLER ◽  
Günter MÜLLER ◽  
Susanne WIED ◽  
Anna CRECELIUS ◽  
Jürgen ECKEL
Keyword(s):  
Adipose Tissue ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Glucose Transport ◽  
Insulin Action ◽  
Kinase Activity ◽  
Signalling Pathways ◽  
Insulin Mimetic ◽  
Isolated Adipocytes ◽  
Stimulation Of

A novel phosphoinositolglycan-peptide (PIG-P) from the yeast Saccharomyces cerevisiae potently mimicks insulin action on glucose transport and metabolism in rat muscle and adipose tissue. The aim of the present study was to elucidate the cellular signalling pathways of this insulin-mimetic compound. Rapid onset and reversibility of PIG-P action on glucose transport were observed in isolated adipocytes with a half-time of transport stimulation of 6-8 min (insulin less than 5 min). Combined treatment with PIG-P and insulin indicated additive stimulation of glucose transport at submaximal concentrations and non-additive action of both agents at maximal doses. The tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) was markedly increased in response to PIG-P in rat cardiomyocytes without any effect on the tyrosine phosphorylation of the insulin receptor β-subunit. PIG-P action in these cells was accompanied by phosphorylation/dephosphorylation of several proteins with molecular masses of 15-30 kDa, a response not detected with insulin. Downstream signalling of IRS-1 was then analysed by monitoring IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity in cardiomyocytes. A stable (2 and 15 min incubation with PIG-P) 7-fold stimulation corresponding to about 50% of insulin action could be detected. Increased tyrosine phosphorylation of IRS-1 and enhanced PI 3-kinase activity in response to PIG-P independent of the insulin receptor was also observed in isolated adipocytes. Involvement of PI 3-kinase in PIG-P action was subsequently confirmed by the dose-dependent inhibition of PIG-P-activated glucose transport in rat diaphragm and adipocytes by the PI 3-kinase inhibitors wortmannin and LY294002. These data suggest divergent upstream signalling by insulin and PIG-P involving phosphoproteins not affected by insulin. However, PIG-P and insulin action converge at the level of IRS-1 inducing insulin-independent PI 3-kinase-mediated signalling to glucose transport.

scholarly journals The effect of malnutrition on insulin binding to rat erythrocytes

1992 ◽  
Vol 67 (2) ◽  
pp. 279-286 ◽  
Author(s):  
Hazel M. Payne-Robinson ◽  
Richard Brown
Keyword(s):  
Insulin Receptor ◽  
Insulin Binding ◽  
Rat Erythrocytes ◽  
Receptor Affinity ◽  
And Control ◽  
Specific Insulin

Insulin binding to erythrocyte receptors was compared in malnourished and control rats. Percentage specific insulin binding to malnourished rat erythrocytes was significantly lower than to control erythrocytes (P < 0.001). The low insulin binding in the malnourished rat erythrocytes was accompanied by low insulin receptor affinity (P = 0.035).

Insulin resistance in polycystic ovary syndrome is associated with defective regulation of ERK1/2 by insulin in skeletal muscle in vivo

2009 ◽  
Vol 418 (3) ◽  
pp. 665-671 ◽  
Author(s):  
Madhurima Rajkhowa ◽  
Sandra Brett ◽  
Daniel J. Cuthbertson ◽  
Christopher Lipina ◽  
Antonio J. Ruiz-Alcaraz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Insulin Signalling ◽  
Polycystic Ovary ◽  
Insulin Stimulation ◽  
Ovary Syndrome ◽  
Stimulation Of

Insulin resistance is a recognized feature of PCOS (polycystic ovary syndrome). However, the molecular reason(s) underlying this reduced cellular insulin sensitivity is not clear. The present study compares the major insulin signalling pathways in skeletal muscle isolated from PCOS and controls. We measured whole-body insulin sensitivity and insulin signalling in skeletal muscle biopsies taken before and after acute exposure to hyperinsulinaemia in nine women diagnosed with PCOS and seven controls. We examined the expression, basal activity and response to in vivo insulin stimulation of three signalling molecules within these human muscle samples, namely IRS-1 (insulin receptor substrate-1), PKB (protein kinase B) and ERK (extracellular-signal-regulated kinase) 1/2. There was no significant difference in the expression, basal activity or activation of IRS-1 or PKB between PCOS and control subjects. However, there was a severe attenuation of insulin stimulation of the ERK pathway in muscle from all but two of the women with PCOS (the two most obese), and an accompanying trend towards higher basal phosphorylation of ERK1/2 in PCOS. These results are striking in that the metabolic actions of insulin are widely believed to require the IRS-1/PKB pathway rather than ERK, and the former has been reported as defective in some previous PCOS studies. Most importantly, the molecular defect identified was independent of adiposity. The altered response of ERK to insulin in PCOS was the most obvious signalling defect associated with insulin resistance in muscle from these patients.

Exercise increases susceptibility of muscle glucose transport to activation by various stimuli

1990 ◽  
Vol 258 (2) ◽  
pp. E390-E393 ◽  
Author(s):  
G. D. Cartee ◽  
J. O. Holloszy
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Sugar Transport ◽  
Insulin Binding ◽  
Insulin Mimetic ◽  
Increased Sensitivity ◽  
Muscle Glucose Transport ◽  
Glucose Analogue ◽  
Stimulation Of

The insulin sensitivity of glucose transport in skeletal muscle is enhanced after exercise. In this study, stimulation of transport of the nonmetabolizable glucose analogue 3-O-methylglucose by the insulin-mimetic agents vanadate and H2O2 was markedly enhanced in rat epitrochlearis muscles 18 h after a bout of swimming. This increase in susceptibility of the glucose transport process in muscle to stimulation by insulin-mimetic agents that act beyond the insulin-binding step provides evidence that the increased insulin sensitivity results from an effect of exercise on a later step in the activation of glucose transport. Hypoxia and insulin appear to stimulate glucose transport by different pathways in muscle as evidenced by an additivity of their maximal effects. The effect of a submaximal hypoxic stimulus on muscle sugar transport was greatly amplified 3 h after exercise. This increase in susceptibility of glucose transport to stimulation by hypoxia after exercise suggests that the increased sensitivity is not limited to the insulin sensitive pathway. In contrast to exercise (i.e., swimming), in vitro muscle contractions did not result in an increase in sensitivity of muscle glucose transport to insulin, raising the possibility that a humoral factor is necessary for this effect.

scholarly journals Tumour-promoting phorbol esters increase basal and inhibit insulin-stimulated lipogenesis in rat adipocytes without decreasing insulin binding

1985 ◽  
Vol 225 (2) ◽  
pp. 523-527 ◽  
Author(s):  
G van de Werve ◽  
J Proietto ◽  
B Jeanrenaud
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Action ◽  
Phorbol Esters ◽  
Insulin Binding ◽  
Rat Adipocytes ◽  
Kinase C ◽  
Dose Dependent ◽  
Isolated Rat ◽  
Stimulation Of

In isolated rat adipocytes, tumour-promoting phorbol esters caused (1) dose-dependent stimulation of lipogenesis in the absence of insulin and (2) inhibition of the lipogenic effect of submaximal concentrations of insulin, but without affecting insulin binding. The possible involvement of protein kinase C in insulin action is discussed.

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.

Enhanced specific insulin binding and insulin action with C-terminal B-chain pentapeptide derived from insulin

FEBS Letters ◽  
1980 ◽  
Vol 119 (1) ◽  
pp. 161-164 ◽  
Author(s):  
K. Kikuchi ◽  
J. Larner ◽  
R. Freer ◽  
A.R. Day
Keyword(s):  
Insulin Action ◽  
Insulin Binding ◽  
Specific Insulin
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