scholarly journals Selectivity of the insulin-like actions of vanadate on glucose and protein metabolism in skeletal muscle

1985 ◽  
Vol 232 (1) ◽  
pp. 273-276 ◽  
Author(s):  
A S Clark ◽  
J M Fagan ◽  
W E Mitch
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Protein Metabolism ◽  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
Metabolic Responses ◽  
Receptor Phosphorylation ◽  
Stimulation Of

To determine if vanadate has insulin-like actions in skeletal muscle, we measured its effects on glucose and protein metabolism in epitrochlearis muscles of rats. Compared with insulin, vanadate increased glucose uptake, glycogen synthesis and glycolysis to a lesser degree, but caused a greater stimulation of lactate and glucose oxidation. Unlike insulin, vanadate did not change either protein synthesis or degradation. These different metabolic responses could be related to the different pattern of insulin-receptor phosphorylation caused by insulin and vanadate.

scholarly journals Insulin-Like Growth Factor I Circumvents Defective Insulin Action in Human Myotonic Dystrophy Skeletal Muscle Cells1

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 4244-4250 ◽  
Author(s):  
Denis Furling ◽  
André Marette ◽  
Jack Puymirat
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Factor I ◽  
Impaired Insulin ◽  
Igf I ◽  
Impaired Insulin Action

Abstract Primary human skeletal muscle cell cultures derived from muscles of a myotonic dystrophy (DM) fetus provided a model in which both resistance to insulin action described in DM patient muscles and the potential ability of insulin-like growth factor I (IGF-I) to circumvent this defect could be investigated. Basal glucose uptake was the same in cultured DM cells as in normal myotubes. In DM cells, a dose of 10 nm insulin produced no stimulatory effect on glucose uptake, and at higher concentrations, stimulation of glucose uptake remained significantly lower than that in normal myotubes. In addition, basal and insulin-mediated protein synthesis were both significantly reduced compared with those in normal cells. In DM myotubes, insulin receptor messenger RNA expression and insulin receptor binding were significantly diminished, whereas the expression of GLUT1 and GLUT4 glucose transporters was not affected. These results indicate that impaired insulin action is retained in DM cultured myotubes. The action of recombinant human IGF-I (rhIGF-I) was evaluated in this cellular model. We showed that rhIGF-I is able to stimulate glucose uptake to a similar extent as in control cells and restore normal protein synthesis level in DM myotubes. Thus, rhIGF-I is able to bypass impaired insulin action in DM myotubes. This provides a solid foundation for the eventual use of rhIGF-I as an effective treatment of muscle weakness and wasting in DM.

Effect of prolactin on 2-deoxyglucose uptake in mouse mammary gland explants

1992 ◽  
Vol 262 (5) ◽  
pp. E627-E630 ◽  
Author(s):  
B. J. Peters ◽  
J. A. Rillema
Keyword(s):  
Protein Synthesis ◽  
Mammary Gland ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Actinomycin D ◽  
Mouse Mammary Gland ◽  
Temporal Response ◽  
Pregnant Mice ◽  
Glucose Analogue ◽  
Stimulation Of

These studies were carried out to explore the possible effect of prolactin (PRL) on glucose uptake into culture mammary gland explants derived from 12- to 14-day pregnant mice. PRL was found to stimulate an increased rate of uptake of a nonmetabolized glucose analogue, 2-[3H]deoxyglucose, into cultured mammary tissues. The onset of this response was 16 h after the addition of PRL, and the response persisted for at least 24 h. A similar temporal response was observed when the PRL stimulation of [14C]glucose oxidation to 14CO2 was determined. The lowest PRL concentration that elicited a stimulation of 2-deoxyglucose uptake was 20 ng/ml, and a maximum response occurred with PRL at a concentration of 250 ng/ml. Ongoing protein synthesis appears to be essential for PRL to express its effect on 2-deoxyglucose transport since cyclohexamide, puromycin, and actinomycin D abolished the PRL response. It is also apparent that the PRL stimulation of 2-deoxyglucose involves activation of a specific carrier-mediated uptake transport system, since the rate of uptake of L-glucose into mouse mammary gland explants was unaffected by PRL.

A novel PKB/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle

2012 ◽  
Vol 447 (1) ◽  
pp. 137-147 ◽  
Author(s):  
Yu-Chiang Lai ◽  
Yang Liu ◽  
Roxane Jacobs ◽  
Mark H. Rider
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Glycogen Synthase ◽  
Insulin Signalling ◽  
Glycogen Synthesis ◽  
Initiation Factor ◽  
Dependent Manner ◽  
Akt Inhibitor

PKB (protein kinase B), also known as Akt, is a key component of insulin signalling. Defects in PKB activation lead to insulin resistance and metabolic disorders, whereas PKB overactivation has been linked to tumour growth. Small-molecule PKB inhibitors have thus been developed for cancer treatment, but also represent useful tools to probe the roles of PKB in insulin action. In the present study, we examined the acute effects of two allosteric PKB inhibitors, MK-2206 and Akti 1/2 (Akti) on PKB signalling in incubated rat soleus muscles. We also assessed the effects of the compounds on insulin-stimulated glucose uptake, glycogen and protein synthesis. MK-2206 dose-dependently inhibited insulin-stimulated PKB phosphorylation, PKBβ activity and phosphorylation of PKB downstream targets (including glycogen synthase kinase-3α/β, proline-rich Akt substrate of 40 kDa and Akt substrate of 160 kDa). Insulin-stimulated glucose uptake, glycogen synthesis and glycogen synthase activity were also decreased by MK-2206 in a dose-dependent manner. Incubation with high doses of MK-2206 (10 μM) inhibited insulin-induced p70 ribosomal protein S6 kinase and 4E-BP1 (eukaryotic initiation factor 4E-binding protein-1) phosphorylation associated with increased eEF2 (eukaryotic elongation factor 2) phosphorylation. In contrast, Akti only modestly inhibited insulin-induced PKB and mTOR (mammalian target of rapamycin) signalling, with little or no effect on glucose uptake and protein synthesis. MK-2206, rather than Akti, would thus be the tool of choice for studying the role of PKB in insulin action in skeletal muscle. The results point to a key role for PKB in mediating insulin-stimulated glucose uptake, glycogen synthesis and protein synthesis in skeletal muscle.

Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle

2008 ◽  
Vol 294 (1) ◽  
pp. E28-E35 ◽  
Author(s):  
Michale Bouskila ◽  
Michael F. Hirshman ◽  
Jørgen Jensen ◽  
Laurie J. Goodyear ◽  
Kei Sakamoto
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Wild Type ◽  
Muscle Glycogen Synthesis ◽  
Mutant Forms

Insulin promotes dephosphorylation and activation of glycogen synthase (GS) by inactivating glycogen synthase kinase (GSK) 3 through phosphorylation. Insulin also promotes glucose uptake and glucose 6-phosphate (G-6- P) production, which allosterically activates GS. The relative importance of these two regulatory mechanisms in the activation of GS in vivo is unknown. The aim of this study was to investigate if dephosphorylation of GS mediated via GSK3 is required for normal glycogen synthesis in skeletal muscle with insulin. We employed GSK3 knockin mice in which wild-type GSK3α and -β genes are replaced with mutant forms (GSK3α/βS21A/S21A/S9A/S9A), which are nonresponsive to insulin. Although insulin failed to promote dephosphorylation and activation of GS in GSK3α/βS21A/S21A/S9A/S9Amice, glycogen content in different muscles from these mice was similar compared with wild-type mice. Basal and epinephrine-stimulated activity of muscle glycogen phosphorylase was comparable between wild-type and GSK3 knockin mice. Incubation of isolated soleus muscle in Krebs buffer containing 5.5 mM glucose in the presence or absence of insulin revealed that the levels of G-6- P, the rate of [14C]glucose incorporation into glycogen, and an increase in total glycogen content were similar between wild-type and GSK3 knockin mice. Injection of glucose containing 2-deoxy-[3H]glucose and [14C]glucose also resulted in similar rates of muscle glucose uptake and glycogen synthesis in vivo between wild-type and GSK3 knockin mice. These results suggest that insulin-mediated inhibition of GSK3 is not a rate-limiting step in muscle glycogen synthesis in mice. This suggests that allosteric regulation of GS by G-6- P may play a key role in insulin-stimulated muscle glycogen synthesis in vivo.

scholarly journals Relationships between urinary inositol excretions and whole-body glucose tolerance and skeletal muscle insulin receptor phosphorylation

Metabolism ◽  
2008 ◽  
Vol 57 (11) ◽  
pp. 1545-1551 ◽  
Author(s):  
April J. Stull ◽  
John P. Thyfault ◽  
Mark D. Haub ◽  
Richard E. Ostlund ◽  
Wayne W. Campbell
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Insulin Receptor ◽  
Whole Body ◽  
Receptor Phosphorylation

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.

Expression of a dominant-negative Ras mutant does not affect stimulation of glucose uptake and glycogen synthesis by insulin

Diabetologia ◽  
1996 ◽  
Vol 39 (5) ◽  
pp. 558-563 ◽  
Author(s):  
J. Dorrestijn ◽  
D. M. Ouwens ◽  
N. Van den Berghe ◽  
J. L. Bos ◽  
J. A. Maassen
Keyword(s):  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Dominant Negative ◽  
Stimulation Of
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