scholarly journals 5′-AMP-activated Protein Kinase Phosphorylates IRS-1 on Ser-789 in Mouse C2C12 Myotubes in Response to 5-Aminoimidazole-4-carboxamide Riboside

2001 ◽  
Vol 276 (50) ◽  
pp. 46912-46916 ◽  
Author(s):  
Søren N. Jakobsen ◽  
D. Grahame Hardie ◽  
Nick Morrice ◽  
Hans E. Tornqvist
Keyword(s):  
Protein Kinase ◽  
Insulin Signaling ◽  
Direct Interaction ◽  
C2c12 Myotubes ◽  
Phosphatidylinositol 3 Kinase ◽  
Increase Insulin Sensitivity ◽  
Effective Form ◽  
Amp Activated Protein Kinase ◽  
Phosphatidylinositol 3

Exercise is known to increase insulin sensitivity and is an effective form of treatment for the hyperglycemia observed in type 2 diabetes. Activation of 5′-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle. Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1). We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR. In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789. This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR. The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR. These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.

scholarly journals Corticotropin-Releasing Hormone Directly Stimulates Thermogenesis in Skeletal Muscle Possibly through Substrate Cycling between de Novo Lipogenesis and Lipid Oxidation

Endocrinology ◽  
2006 ◽  
Vol 147 (1) ◽  
pp. 31-38 ◽  
Author(s):  
G. Solinas ◽  
S. Summermatter ◽  
D. Mainieri ◽  
M. Gubler ◽  
J. P. Montani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Lipid Oxidation ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Phosphatidylinositol 3 Kinase ◽  
Intact Mouse ◽  
Amp Activated Protein Kinase ◽  
Protein Kinase Signaling ◽  
Phosphatidylinositol 3

The mechanisms by which CRH and related peptides (i.e. the CRH/urocortin system) exert their control over thermogenesis and weight regulation have until now focused only upon their effects on brain centers controlling sympathetic outflow. Using a method that involves repeated oxygen uptake determinations in intact mouse skeletal muscle, we report here that CRH can act directly on skeletal muscle to stimulate thermogenesis, an effect that is more pronounced in oxidative than in glycolytic muscles and that can be inhibited by a selective CRH-R2 antagonist or blunted by a nonselective CRH receptor antagonist. This thermogenic effect of CRH can also be blocked by interference along pathways of de novo lipogenesis and lipid oxidation, as well as by inhibitors of phosphatidylinositol 3-kinase or AMP-activated protein kinase. Taken together, these studies demonstrate that CRH can directly stimulate thermogenesis in skeletal muscle, and in addition raise the possibility that this thermogenic effect, which requires both phosphatidylinositol 3-kinase and AMP-activated protein kinase signaling, might occur via substrate cycling between de novo lipogenesis and lipid oxidation. The effect of CRH in directly stimulating thermogenesis in skeletal muscle underscores a potentially important peripheral role for the CRH/urocortin system in the control of thermogenesis in this tissue, in its protection against excessive intramyocellular lipid storage, and hence against skeletal muscle lipotoxicity and insulin resistance.

Phosphatidylinositol 3-kinase Glu545Lys and His1047Tyr Mutations are not Associated with T2D

2020 ◽  
Vol 16 (8) ◽  
pp. 881-888 ◽  
Author(s):  
Imadeldin Elfaki ◽  
Rashid Mir ◽  
Faisel M. Abu-Duhier ◽  
Roaid Khan ◽  
Mohammed Sakran
Keyword(s):  
Insulin Signaling ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Phosphatidylinositol 3 Kinase ◽  
Single Nucleotide ◽  
Peripheral Tissues ◽  
Different Populations ◽  
Larger Sample ◽  
Phosphatidylinositol 3

Background: Insulin resistance initiated in peripheral tissues induces type 2 diabetes (T2D). It occurs when insulin signaling is impaired. Introduction: Phosphatidylinositol 3-kinases (PI3K) are important for insulin signaling. Single nucleotide polymorphisms of the PI3K gene have been associated with T2D. Methods: We have investigated the association of Glu545Lys and His1047Tyr mutations of phosphatidylinositol- 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene with T2D. We have screened 103 T2D patients and 132 controls for Glu545Lys mutation, and 101 T2D patients and 103 controls for the His1047Tyr mutation from a Saudi cohort using AS-PCR. Results: Our results indicated that there is no association between the GA genotype of rs104886003 (Glu545Lys) and T2D, OR= 0.15 (95% CI: 0.007-3.28), RR= 0.29(0.02-3.72), P value= 0.23. The A allele is also not associated with T2D diabetes, OR= 1.01(95% CI: 0.70-1.46), RR=1.00(0.85-1.18), P value=0.91. Results showed that CT genotype of rs121913281 (His1047Tyr) was not associated with T2D, OR=0.94(95% CI: 0.23-3.9), RR= 0.97(0.48-1.97), P-value = 0.94, and T allele was also not associated with T2D, OR=1.06 (95% CI: 0.71-1.56), RR= 1.02(0.84-1.24), P-value =0.76. Conclusion: We conclude that the A allele of rs104886003 may not be associated with T2D. The T allele of rs121913281 may also not associated with T2D. However, future studies with larger sample sizes and in different populations are recommended.

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