scholarly journals Insulin Increases Ceramide Synthesis in Skeletal Muscle

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
M. E. Hansen ◽  
T. S. Tippetts ◽  
M. C. Anderson ◽  
Z. E. Holub ◽  
E. R. Moulton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Cells ◽  
Insulin Injection ◽  
Sphingolipid Metabolism ◽  
Anabolic Effect ◽  
Potential Mechanism ◽  
Ceramide Synthesis ◽  
Time Periods ◽  
Ceramide Accumulation ◽  
Novel Therapeutic

Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle.Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG) were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis.Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals.Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects.

scholarly journals Antioxidants Supplementation Reduces Ceramide Synthesis Improving the Cardiac Insulin Transduction Pathway in a Rodent Model of Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3413
Author(s):  
Katarzyna Hodun ◽  
Klaudia Sztolsztener ◽  
Adrian Chabowski
Keyword(s):  
Lipid Metabolism ◽  
Insulin Signaling ◽  
High Performance ◽  
Sphingolipid Metabolism ◽  
Intragastric Administration ◽  
Transduction Pathway ◽  
Ceramide Synthesis ◽  
Sphingosine 1 Phosphate ◽  
Male Wistar Rats ◽  
Ceramide Accumulation

Obesity-related disruption in lipid metabolism contributes to cardiovascular dysfunction. Despite numerous studies on lipid metabolism in the left ventricle, there is no data describing the influence of n-acetylcysteine (NAC) and α-lipoic acid (ALA), as glutathione precursors, on sphingolipid metabolism, and insulin resistance (IR) occurrence. The aim of our experiment was to evaluate the influence of chronic antioxidants administration on myocardial sphingolipid state and intracellular insulin signaling as a potential therapeutic strategy for obesity-related cardiovascular IR. The experiment was conducted on male Wistar rats fed a standard rodent chow or a high-fat diet with intragastric administration of NAC or ALA for eight weeks. Cardiac and plasma sphingolipid species were assessed by high-performance liquid chromatography (HPLC). The proteins expressed from sphingolipid and insulin signaling pathways were determined by Western blot. Antioxidant supplementation markedly reduced ceramide accumulation by lowering the expression of selected proteins from the sphingolipid pathway and simultaneously increased the myocardial sphingosine-1-phosphate level. Moreover, NAC and ALA augmented the expression of GLUT4 and the phosphorylation state of Akt (Ser473) and GSK3β (Ser9), which improved the intracellular insulin transduction pathway. Based on our results, we may postulate that NAC and ALA have a beneficial influence on the cardiac ceramidose under IR conditions.

scholarly journals Intracellular ceramide synthesis and protein kinase Cζ activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells

2004 ◽  
Vol 382 (2) ◽  
pp. 619-629 ◽  
Author(s):  
Darren J. POWELL ◽  
Sophie TURBAN ◽  
Alexander GRAY ◽  
Eric HAJDUCH ◽  
Harinder S. HUNDAL
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Transport ◽  
Insulin Signalling ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
L6 Myotubes ◽  
Skeletal Muscle Insulin Resistance ◽  
Ceramide Synthesis

Non-esterified fatty acids (NEFAs) have been implicated in the pathogenesis of skeletal muscle insulin resistance that may develop, in part, as a consequence of a direct inhibitory effect on early insulin signalling events. Here we report work investigating the mechanism by which palmitate (a saturated free fatty acid) inhibits insulin action in rat L6 myotubes. Palmitate suppressed the insulin-induced plasma membrane recruitment and phosphorylation of protein kinase B (PKB) and this was associated with a loss in insulin-stimulated glucose transport. The inhibition in PKB was not due to a loss in insulin receptor substrate (IRS)1 tyrosine phosphorylation, IRS-1/p85 (phosphoinositide 3-kinase) association or suppression in phosphatidyl 3,4,5 triphosphate synthesis, but was attributable to an elevated intracellular synthesis of ceramide (6-fold) from palmitate and a concomitant activation of protein kinase PKCζ (5-fold). Inhibitors of serine palmitoyl transferase suppressed the intracellular synthesis of ceramide from palmitate, prevented PKCζ activation, and antagonized the inhibition in PKB recruitment/phosphorylation and the loss in insulin-stimulated glucose transport elicited by the NEFA. Inhibiting the palmitate-induced activation of PKCζ with Ro 31.8220, also prevented the loss in the insulin-dependent phosphorylation of PKB caused by palmitate. These findings indicate that intracellular ceramide synthesis and PKCζ activation are important aspects of the mechanism by which palmitate desensitizes L6 muscle cells to insulin.

Extracts of Hymenocardia acida ameliorate insulin resistance in skeletal muscle cells

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
II Ezeigbo ◽  
C Wheeler-Jones ◽  
S Gibbons ◽  
ME Cleasby
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Ameliorate Insulin Resistance

TGFß regulates metabolism of human skeletal muscle cells by miRNAs

2018 ◽  
Author(s):  
S Höckele ◽  
P Huypens ◽  
C Hoffmann ◽  
T Jeske ◽  
M Hastreiter ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells

1878-P: The Role and Potential Mechanism of LncRNA Gm15441 in Skeletal Muscle Glucose and Lipid Metabolism

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1878-P
Author(s):  
LIANGHUI YOU ◽  
YU ZENG ◽  
NAN GU ◽  
CHENBO JI
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Potential Mechanism ◽  
Glucose And Lipid Metabolism
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