scholarly journals Insulin action on adipocytes. Evidence that the anti-lipolytic and lipogenic effects of insulin are mediated by the same receptor

1979 ◽  
Vol 184 (2) ◽  
pp. 355-360 ◽  
Author(s):  
S H L Thomas ◽  
M H Wisher ◽  
D Brandenburg ◽  
P H Sönksen
Keyword(s):  
Dose Response ◽  
Insulin Action ◽  
Insulin Analogues ◽  
Bovine Insulin ◽  
Maximal Effect ◽  
Maximal Concentration ◽  
Insulin Stimulation ◽  
Chemically Modified ◽  
Chemically Modified Insulins ◽  
Stimulation Of

1. The dose-response relationships of insulin stimulation of lipogenesis and inhibition of lipolysis were studied simultaneously by using rat adipocytes to determine whether these different effects of insulin are mediated through the same or different sets of receptors. 2. The sensitivity (defined as the concentration of insulin required to produce a half-maximal effect) of the stimulated lipogenic response to insulin was not significantly different from the sensitivity of the anti-lipolytic response to insulin. The addition of different adrenaline and glucose concentrations did not alter the half-maximal concentration of insulin required to inhibit lipolysis. 3. The specificities of the lipogenic and antilipolytic responses were studied by using insulin analogues. The sensitivities of the lipogenic and anti-lipolytic responses were the same for five chemically modified insulins and hagfish insulin, which have potencies compared with bovine insulin of between 3 and 90%. 4. Starving rats for 48h significantly increased the sensitivities of both the antilipolytic and lipogenic responses to insulin, but the changes in the sensitivities of both lipogenesis and anti-lipolysis returned to that of fed rats. 5. We conclude that insulin stimulates lipogenesis and inhibits lipolysis over the same concentration range. These observations provide powerful evidence that the different effects of insulin are mediated through the same set of receptors.

scholarly journals Insulin stimulation of pyruvate dehydrogenase in adipocytes involves two distinct signalling pathways

2003 ◽  
Vol 369 (2) ◽  
pp. 351-356 ◽  
Author(s):  
Sam A. JOHNSON ◽  
Richard M. DENTON
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Maximal Effect ◽  
Insulin Stimulation ◽  
Rat Adipocytes ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Phosphoinositide 3 Kinase ◽  
Stimulation Of

In isolated rat adipocytes, the insulin stimulation of pyruvate dehydrogenase can be partially inhibited by inhibitors of PI3K (phosphoinositide 3-kinase) and MEK1/2 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase). In combination, U0126 and wortmannin completely block the insulin stimulation of pyruvate dehydrogenase. It is concluded that the effect of insulin on pyruvate dehydrogenase in rat adipocytes involves two distinct signalling pathways: one is sensitive to wortmannin and the other to U0126. The synthetic phosphoinositolglycan PIG41 can activate pyruvate dehydrogenase but the activation is only approx. 30% of the maximal effect of insulin. This modest activation can be completely blocked by wortmannin alone, suggesting that PIG41 acts through only one of the pathways leading to the activation of pyruvate dehydrogenase.

Mechanism of insulin-induced activation of Na(+)-K(+)-ATPase in isolated rat soleus muscle

1991 ◽  
Vol 261 (2) ◽  
pp. C224-C230 ◽  
Author(s):  
E. Weil ◽  
S. Sasson ◽  
Y. Gutman
Keyword(s):  
Soleus Muscle ◽  
Time Course ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Insulin Stimulation ◽  
K Uptake ◽  
Sequence Of Events ◽  
Rat Soleus Muscle ◽  
Isolated Rat ◽  
Stimulation Of

Insulin augments Na(+)-K(+)-ATPase activity in skeletal muscles. It has been proposed that the sequence of events is activation of Na(+)-H+ antiporter, increased intracellular Na+ concentration ( [Na+]i), and stimulation of Na(+)-K+ pump. We have used isolated rat soleus muscles to test this hypothesis. Insulin increased the ouabain-suppressible K+ uptake in a dose- and time-dependent manner. The maximal effect was observed at 50-100 mU/ml insulin. Stimulation of K+ uptake was accompanied by increased specific [3H]ouabain binding and lowered [Na+]i. The ionophore monensin, which promotes Na(+)-H+ exchange, also increased the rate of ouabain-suppressible K+ uptake in soleus muscle, with a maximal effect obtained at 10-100 microM ionophore. However, this increase was accompanied by an elevation of [Na+]i. In the presence of 10-100 microM monensin, addition of 100 mU/ml insulin further increased K+ uptake but reduced [Na+]i. The effect on K+ uptake was additive. Ouabain (10(-3) M) completely suppressed the effect of insulin on [Na+]i. Insulin had no effect on the magnitude or the time course of insulin stimulation of K+ uptake. Thus equal stimulation of Na(+)-K(+)-ATPase by insulin was observed when [Na+]i was elevated (under monensin) or lowered (under amiloride). These data suggest that activation of Na(+)-K(+)-ATPase in soleus muscle by insulin is not secondary to stimulation of Na(+)-H+ antiporter.

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.

Is intracellular Ca2+ involved in insulin stimulation of sugar transport? Fact and prejudice

1984 ◽  
Vol 62 (11) ◽  
pp. 1228-1236 ◽  
Author(s):  
Amira Klip
Keyword(s):  
Plasma Membrane ◽  
Glucose Transport ◽  
Insulin Action ◽  
Sugar Transport ◽  
Muscle Cells ◽  
Fat Tissue ◽  
Insulin Stimulation ◽  
Hormonal Response ◽  
L6 Muscle Cells ◽  
Stimulation Of

Insulin stimulates the rate of glucose transport in muscle and fat tissue by incorporation of transporters from internal membranes into the plasma membrane. It is conceivable that cell Ca2+ ions could play a role in transporter translocation. Indeed Ca2+ has been thought to mediate insulin action, but the evidence remains highly controversial. Experiments to this effect include (i) determinations of a requirement for extracellular Ca2+ in the hormonal response, (ii) stimulation of glucose transport by agents thought to elevate cytosolic Ca2+, [Ca2+]i, and (iii) determinations of Ca2+ efflux. Actual measurements of the effect of insulin on [Ca2+]i were missing until recently. Current methods to measure [Ca2+]i include Ca2+-selective intracellular electrodes, metallochromic dyes, and photoproteins. Main drawbacks of these procedures have been the requirement of microinjection for their incorporation, which restricts their use to large cells, and their interaction with cytoplasmic Mg2+ and H+. Recently, a fluorescent Ca2+ chelator, quin-2, has been devised, which circumvents these difficulties. A permeable, non-chelating precursor of quin-2 penetrates cells and once in the cytosol becomes an impermeant, fluorescent Ca2+ chelator. With this technique it was shown that insulin does not change [Ca2+]i while stimulating glucose transport in L6 muscle cells.

Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle

2000 ◽  
Vol 279 (1) ◽  
pp. E206-E212 ◽  
Author(s):  
Luis F. Del Aguila ◽  
Raj K. Krishnan ◽  
Jan S. Ulbrecht ◽  
Peter A. Farrell ◽  
Pamela H. Correll ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Muscle Damage ◽  
Insulin Action ◽  
Molecular Mechanisms ◽  
Physiological Stress ◽  
Serine Phosphorylation ◽  
Insulin Stimulation ◽  
Akt Kinase ◽  
Tnf Α ◽  
Stimulation Of

Physiological stress associated with muscle damage results in systemic insulin resistance. However, the mechanisms responsible for the insulin resistance are not known; therefore, the present study was conducted to elucidate the molecular mechanisms associated with insulin resistance after muscle damage. Muscle biopsies were obtained before (base) and at 1 h during a hyperinsulinemic-euglycemic clamp (40 mU · kg−1 · min−1) in eight young (age 24 ± 1 yr) healthy sedentary (maximal O2 consumption, 49.7 ± 2.4 ml · kg−1 · min−1) males before and 24 h after eccentric exercise (ECC)-induced muscle damage. To determine the role of cytokines in ECC-induced insulin resistance, venous blood samples were obtained before (control) and 24 h after ECC to evaluate ex vivo endotoxin-induced mononuclear cell secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Glucose disposal was 19% lower after ECC ( P < 0.05). Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation was 45% lower after ECC ( P < 0.05). Insulin-stimulated phosphatidylinositol (PI) 3-kinase, Akt (protein kinase B) serine phosphorylation, and Akt activity were reduced 34, 65, and 20%, respectively, after ECC ( P < 0.05). TNF-α, but not IL-6 or IL-1β production, increased 2.4-fold 24 h after ECC ( P < 0.05). TNF-α production was positively correlated with reduced insulin action on PI 3-kinase ( r = 0.77, P = 0.04). In summary, the physiological stress associated with muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase, presumably leading to decreased insulin-mediated glucose uptake. Although more research is needed on the potential role for TNF-α inhibition of insulin action, elevated TNF-α production after muscle damage may impair insulin signal transduction.

Insulin activation of brain Na(+)-K(+)-ATPase is mediated by alpha 2-form of enzyme

1990 ◽  
Vol 258 (5) ◽  
pp. C812-C817 ◽  
Author(s):  
J. L. Brodsky
Keyword(s):  
Dose Response ◽  
Cardiac Glycoside ◽  
Insulin Action ◽  
Response Curve ◽  
Sodium Influx ◽  
Insulin Effect ◽  
High Affinity ◽  
The Brain ◽  
Stimulation Of

The sensitivity of the synaptosomal Na(+)-K(+)-ATPase to insulin was examined and found to be stimulated by the hormone when physiological intracellular sodium concentrations were present. Activation was not mediated by a sodium influx into the vesicles, as shown using sodium uptake experiments and by the fact that tetrodotoxin did not inhibit insulin action. Because the brain Na(+)-K(+)-ATPase catalytic subunit exists as two forms with different affinities for the inhibitory cardiac glycoside ouabain, the sensitivity of each form for insulin was examined. As previously observed in adipocytes, only the high-affinity component, alpha 2, was insulin sensitive. A dose-response curve of insulin activation of the Na(+)-K(+)-ATPase demonstrated a maximal insulin effect at relatively high hormone concentrations. It is unknown, therefore, whether stimulation of the brain Na(+)-K(+)-ATPase occurs in vivo.

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