Polymyxin B selectively inhibits insulin effects on transport in isolated muscle

1987 ◽  
Vol 252 (2) ◽  
pp. E248-E254
Author(s):  
T. Gremeaux ◽  
J. F. Tanti ◽  
E. Van Obberghen ◽  
Y. Le Marchand-Brustel
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Glycogen Synthase ◽  
Polymyxin B ◽  
Acid Uptake ◽  
Insulin Effect ◽  
Insulin Receptor Tyrosine Kinase ◽  
Free System

Polymyxin B (PMB), a cyclic decapeptide antibiotic, inhibits the hypoglycemic effect of insulin in vivo. To elucidate the mechanism of PMB action, we have studied its effect in vitro on insulin-stimulated pathways in the mouse skeletal muscle. PMB, added to the incubation mixture, specifically inhibited insulin-stimulated 2-deoxyglucose transport and alpha-aminoisobutyric acid uptake in the isolated soleus muscle but did not affect the basal rates of transport (measured in the absence of insulin). PMB did not alter insulin binding and hexokinase activity. PMB effect was observed at all deoxyglucose concentrations tested, and PMB was also able to inhibit vanadate-stimulated glucose transport. By contrast, insulin activation of glycogen synthase was not prevented by PMB. Basal and maximally insulin-stimulated insulin receptor tyrosine kinase activity, tested in a cell-free system, was similar for both autophosphorylation and phosphorylation of exogenous substrates in the absence or in the presence of PMB. Furthermore, the insulin sensitivity of the kinase was increased in the presence of PMB. Our results suggest that the anti-insulin effect of PMB observed in vivo is due to an inhibition of insulin-stimulated glucose transport in the skeletal muscle perhaps through a specific blockade of the insulin-induced translocation of the glucose carriers.

Palmitate oxidation rate and action on glycogen synthase in myoblasts from insulin-resistant subjects

2000 ◽  
Vol 279 (3) ◽  
pp. E561-E569 ◽  
Author(s):  
David M. Mott ◽  
Cristen Hoyt ◽  
Rael Caspari ◽  
Karen Stone ◽  
Richard Pratley ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glycogen Synthase ◽  
Glucose Disposal ◽  
Nonesterified Fatty Acid ◽  
Palmitate Oxidation ◽  
Oxidation Rates ◽  
Glycogen Synthase Activity

Elevated plasma lipid and nonesterified fatty acid concentrations reduce insulin-mediated glucose disposal in skeletal muscle. Cultured myoblasts from 21 subjects were studied for rates of palmitate oxidation and the effect of palmitate on glycogen synthase activity at the end of an 18-h incubation in serum- and glucose-free media. Oxidation rates of 40 μM palmitate in cultured myoblasts correlated with the fasting glucose ( r = 0.71, P = 0.001), log fasting insulin ( r = 0.52, P = 0.03), and insulin-mediated glucose storage rate ( r = −0.50, P = 0.04) of the muscle donors. Myoblast glycogen synthase activity can be regulated by 240 μM palmitate, but the changes are associated with the basal respiratory quotient and not with the insulin resistance of the muscle donor. These results indicate that myoblasts producing elevated palmitate oxidation rates in vitro can be used to identify skeletal muscle abnormalities which are primary contributors to insulin resistance in vivo. Effects of 240 μM palmitate on myoblast glycogen synthase activity appear to be mechanistically different from the relationship between myoblast palmitate oxidation rates and insulin resistance of the muscle donor.

In vivo regulation of protein-serine kinases by insulin in skeletal muscle of fructose-hypertensive rats

1999 ◽  
Vol 277 (2) ◽  
pp. E299-E307 ◽  
Author(s):  
Sanjay Bhanot ◽  
Baljinder S. Salh ◽  
Subodh Verma ◽  
John H. McNeill ◽  
Steven L. Pelech
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Synthase ◽  
Insulin Injection ◽  
Glycogen Synthase Kinase 3 ◽  
Phosphatidylinositol 3 Kinase ◽  
S6 Kinase ◽  
Serine Kinases ◽  
Gsk 3Β

The effects of tail-vein insulin injection (2 U/kg) on the regulation of protein-serine kinases in hindlimb skeletal muscle were investigated in hyperinsulinemic hypertensive fructose-fed (FF) animals that had been fasted overnight. Basal protein kinase B (PKB) activity was elevated about twofold in FF rats and was not further stimulated by insulin. Phosphatidylinositol 3-kinase (PI3K), which lies upstream of PKB, was increased ∼3.5-fold within 2–5 min by insulin in control rats. Basal and insulin-activated PI3K activities were further enhanced up to 2-fold and 1.3-fold, respectively, in FF rats. The 70-kDa S6 kinase (S6K) was stimulated about twofold by insulin in control rats. Both basal and insulin-stimulated S6K activity was further enhanced up to 1.5-fold and 3.5-fold, respectively, in FF rats. In control rats, insulin caused a 40–50% reduction of the phosphotransferase activity of the β-isoform of glycogen synthase kinase 3 (GSK-3β), which is a PKB target in vitro. Basal GSK-3β activity was decreased by ∼40% in FF rats and remained unchanged after insulin treatment. In summary, 1) the PI3K → PKB → S6K pathway was upregulated under basal conditions, and 2) insulin stimulation of PI3K and S6K activities was enhanced, but both PKB and GSK-3 were refractory to the effects of insulin in FF rats.

scholarly journals Selective Glycogen Synthase Kinase 3 Inhibitors Potentiate Insulin Activation of Glucose Transport and Utilization In Vitro and In Vivo

Diabetes ◽  
2003 ◽  
Vol 52 (3) ◽  
pp. 588-595 ◽  
Author(s):  
D. B. Ring ◽  
K. W. Johnson ◽  
E. J. Henriksen ◽  
J. M. Nuss ◽  
D. Goff ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3

scholarly journals Effects of prolonged elevation of plasma adrenaline concentration in vivo on insulin-sensitivity in soleus muscle of the rat

1987 ◽  
Vol 244 (3) ◽  
pp. 655-660 ◽  
Author(s):  
L Budohoski ◽  
R A Challiss ◽  
A Dubaniewicz ◽  
H Kaciuba-Usciłko ◽  
B Leighton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Biochemical Basis ◽  
Plasma Adrenaline ◽  
Skeletal Muscle Insulin Sensitivity

1. Prolonged elevation of the plasma adrenaline concentration was produced in rats by implantation of adrenaline-releasing retard-tablets. With this technique, a hyperadrenalinaemic state is maintained for at least 5 days. 2. At 6 h after implantation of the retard-tablet it was found that plasma glucose and fatty acid concentrations increased and insulin concentration decreased compared with values obtained from placebo-tablet-implanted rats. Administration of a subcutaneous glucose load demonstrated an impaired glucose tolerance in vivo, and incubation of soleus muscle strips from 6 h-hyperadrenalinaemic rats in vitro demonstrated a decreased sensitivity of the rates of glycolysis and glucose transport to insulin. 3. The sensitivities of the rates of glycolysis, glucose transport and glycogen synthesis to insulin were determined for the incubated soleus muscle preparation isolated from animals after 48 h, 72 h and 120 h duration of hyperadrenalinaemia. At 48 h after retard-tablet implantation, the sensitivity of the processes of glucose transport and glycolysis was decreased; at 72 h, the insulin-sensitivities of the rates of glycolysis and glucose transport in skeletal muscle were similar to those determined for control animals; at 120 h, however, the sensitivities of the processes of glucose transport and glycolysis were both statistically significantly increased. In contrast, no changes in the sensitivity of the process of glycogen synthesis were observed at any of the time intervals studied. 4. The possible biochemical basis for the observed changes in skeletal-muscle insulin-sensitivity with prolonged hyperadrenalinaemia is discussed.

Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle

2001 ◽  
Vol 281 (1) ◽  
pp. E8-E15 ◽  
Author(s):  
Yenshou Lin ◽  
Samar I. Itani ◽  
Theodore G. Kurowski ◽  
David J. Dean ◽  
Zhijun Luo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Transport ◽  
Insulin Signaling ◽  
Phorbol Esters ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Insulin Receptor Tyrosine Kinase ◽  
Pkc Isoforms ◽  
Glucose Incorporation

Numerous studies have shown a correlation between changes in protein kinase C (PKC) distribution and/or activity and insulin resistance in skeletal muscle. To investigate which PKC isoforms might be involved and how they affect insulin action and signaling, studies were carried out in rat soleus muscle incubated with phorbol esters. Muscles preincubated for 1 h with 1 μM phorbol 12,13-dibutyrate (PDBu) showed an impaired ability of insulin to stimulate glucose incorporation into glycogen and a translocation of PKC-α, -βI, -θ, and -ε, and probably -βII, from the cytosol to membranes. Preincubation with 1 μM PDBu decreased activation of the insulin receptor tyrosine kinase by insulin and to an even greater extent the phosphorylation of Akt/protein kinase B and glycogen synthase kinase-3. However, it failed to diminish the activation of phosphatidylinositol 3′-kinase by insulin. Despite these changes in signaling, the stimulation by insulin of glucose transport (2-deoxyglucose uptake) and glucose incorporation into lipid and oxidation to CO2 was unaffected. The results indicate that preincubation of skeletal muscle with phorbol ester leads to a translocation of multiple conventional and novel PKC isoforms and to an impairment of several, but not all, events in the insulin-signaling cascade. They also demonstrate that these changes are associated with an inhibition of insulin-stimulated glycogen synthesis but that, at the concentration of PDBu used here, glucose transport, its incorporation into lipid, and its oxidation to CO2 are unaffected.

Insulin binding and glucose transport activity in cardiomyocytes of a diabetic rat

1986 ◽  
Vol 250 (4) ◽  
pp. E402-E406 ◽  
Author(s):  
E. C. Almira ◽  
A. R. Garcia ◽  
B. R. Boshell
Keyword(s):  
Glucose Transport ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Heart Cells ◽  
Apparent Difference ◽  
Insulin Effect ◽  
Streptozotocin Induced Diabetes

We studied insulin binding and glucose transport in isolated adult cardiomyocytes from rats with 2-wk streptozotocin-induced diabetes. At 37 degrees C, cells from diabetic rats bound less 125I-insulin and exhibited lower rates of 3-O-methylglucose transport than cells from control rats. In contrast, the amount of 125I-insulin bound to myocytes at 4 degrees C was the same in both groups. Preincubation of cells from both groups with 10-10,000 ng/ml insulin significantly increased their basal rates of glucose transport by approximately 40%. However, the augmented rates in diabetics were still approximately 36% lower than the corresponding insulin-stimulated rates in the controls. When the glucose transport data were expressed as percent maximal insulin effect and plotted as a function of the amount of insulin bound, the curves obtained from both diabetic and nondiabetic controls were superimposable. These data demonstrate that 1) heart cells from diabetic rats bind less insulin than from control rats under conditions in which they exhibit impaired glucose transport rates, 2) there is no apparent difference in total receptor number between the two groups, but internalization of intact insulin appears to be diminished in diabetes, 3) coupling exists between insulin binding and glucose transport in both groups, and 4) these impaired processes are completely reversed by insulin treatment in vivo but not in vitro.

Transgenic models – a scientific tool to understand exercise-induced metabolism: the regulatory role of AMPK (5′-AMP-activated protein kinase) in glucose transport and glycogen synthase activity in skeletal muscle

2003 ◽  
Vol 31 (6) ◽  
pp. 1290-1294 ◽  
Author(s):  
J.F.P. Wojtaszewski ◽  
J.N. Nielsen ◽  
S.B. Jørgensen ◽  
C. Frøsig ◽  
J.B. Birk ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Transport ◽  
Glycogen Synthase ◽  
Muscle Metabolism ◽  
Regulatory Role ◽  
Amp Activated Protein Kinase ◽  
Glycogen Synthase Activity

The AMPK (5´AMP-activated protein kinase) is becoming recognized as a critical regulator of energy metabolism. However, many of these effects in muscle metabolism have been ascribed to AMPK based on the use of the unspecific activator AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside). Using mouse models in which AMPK activity has been specifically blocked (kinase dead) or knocked out we and others have been able to conduct studies gaining more conclusive data on the role of AMPK in muscle metabolism. In this mini-review focus is on AMPK and its regulatory role for glucose transport and GS (glycogen synthase) activity in skeletal muscle, indicating that AMPK is a GS kinase in vivo which might influence GS activity during exercise and that AMPK is involved in AICAR/hypoxia-induced glucose transport but not or only partially in contraction-stimulated glucose transport.

In vitro simulation of calorie restriction-induced decline in glucose and insulin leads to increased insulin-stimulated glucose transport in rat skeletal muscle

2007 ◽  
Vol 293 (6) ◽  
pp. E1782-E1788 ◽  
Author(s):  
Edward B. Arias ◽  
Gregory D. Cartee
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Calorie Restriction ◽  
Serine Phosphorylation ◽  
Rat Skeletal Muscle ◽  
Extracellular Glucose ◽  
In Vitro Simulation

In vivo calorie restriction [CR; consuming 60% of ad libitum (AL) intake] induces elevated insulin-stimulated glucose transport (GT) in skeletal muscle. The mechanisms triggering this adaptation are unknown. The aim of this study was to determine whether physiological reductions in extracellular glucose and/or insulin, similar to those found with in vivo CR, were sufficient to elevate GT in isolated muscles. Epitrochlearis muscles dissected from rats were incubated for 24 h in media with glucose (8 mM) and insulin (80 μU/ml) at levels similar to plasma values of AL-fed rats and compared with muscles incubated with glucose (5.5 mM) and/or insulin (20 μU/ml) at levels similar to plasma values of CR rats. Muscles incubated with CR levels of glucose and insulin for 24 h had a subsequently greater ( P < 0.005) GT with 80 μU/ml insulin and 8 mM [3H]-3- O-methylglucose but unchanged GT without insulin. Reducing only glucose or insulin for 24 h or both glucose and insulin for 6 h did not induce altered GT. Increased GT after 24-h incubation with CR levels of glucose and insulin was not attributable to increased insulin receptor tyrosine phosphorylation, Akt serine phosphorylation, or Akt substrate of 160 kDa phosphorylation. Nor did 24-h incubation with CR levels of glucose and insulin alter the abundance of insulin receptor, insulin receptor substrate-1, GLUT1, or GLUT4 proteins. These results provide the proof of principle that reductions in extracellular glucose and insulin, similar to in vivo CR, are sufficient to induce an increase in insulin-stimulated glucose transport comparable to the increase found with in vivo CR.

scholarly journals Glucose-transporter (GLUT4) protein content in oxidative and glycolytic skeletal muscles from calf and goat

1995 ◽  
Vol 305 (2) ◽  
pp. 465-470 ◽  
Author(s):  
J F Hocquette ◽  
F Bornes ◽  
M Balage ◽  
P Ferre ◽  
J Grizard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Transporter Protein ◽  
Rat Muscle ◽  
Glucose Transporter Glut4

It is well accepted that skeletal muscle is a major glucose-utilizing tissue and that insulin is able to stimulate in vivo glucose utilization in ruminants as in monogastrics. In order to determine precisely how glucose uptake is controlled in various ruminant muscles, particularly by insulin, this study was designed to investigate in vitro glucose transport and insulin-regulatable glucose-transporter protein (GLUT4) in muscle from calf and goat. Our data demonstrate that glucose transport is the rate-limiting step for glucose uptake in bovine fibre strips, as in rat muscle. Insulin increases the rate of in vitro glucose transport in bovine muscle, but to a lower extent than in rat muscle. A GLUT4-like protein was detected by immunoblot assay in all insulin-responsive tissues from calf and goat (heart, skeletal muscle, adipose tissue) but not in liver, brain, erythrocytes and intestine. Unlike the rat, bovine and goat GLUT4 content is higher in glycolytic and oxido-glycolytic muscles than in oxidative muscles. In conclusion, using both a functional test (insulin stimulation of glucose transport) and an immunological approach, this study demonstrates that ruminant muscles express GLUT4 protein. Our data also suggest that, in ruminants, glucose is the main energy-yielding substrate for glycolytic but not for oxidative muscles, and that insulin responsiveness may be lower in oxidative than in other skeletal muscles.

scholarly journals Sodium plus Potassium-Activated, Ouabain-Inhibited AdenosineTriphosphatase from a Fraction of Rat Skeletal Muscle, and Lack of Insulin Effect on It

1969 ◽  
Vol 54 (2) ◽  
pp. 188-202 ◽  
Author(s):  
Ellen Rogus ◽  
Thomas Price ◽  
Kenneth L. Zierler
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Enzyme System ◽  
Human Muscle ◽  
Rat Skeletal Muscle ◽  
Ph Optimum ◽  
Insulin Effect ◽  
Na Efflux

An ATPase, activated by Na+ plus K+ in the presence of Mg++ and inhibited by ouabain, has been obtained from rat skeletal muscle. Unlike ATPase's with similar properties obtained from other preparations, this ATPase was found only in the fraction containing fragmented sarcoplasmic reticulum. It is suggested that in rat skeletal muscle this ATPase may reside in sarcoplasmic reticulum and not in sarcolemma. This ATPase differed in its pH optimum and in its cation sensitivity from that of rat brain and from that of human muscle reported by Samaha and Gergely (1965, 1966). Because insulin accelerates Na+ efflux from muscle, efforts were made to determine whether or not this effect of insulin could be attributed to increased Na+ + K+-activated ATPase activity. Insulin, administered either in vivo or in vitro, had no demonstrable effect on the enzyme system, nor did it protect against inhibition by ouabain.

Sign in / Sign up

Export Citation Format

Share Document