A critical role for the small GTPase Rac1 in insulin signaling that regulates glucose uptake in skeletal muscle

Satoh, Takaya; Takenaka, Nobuyuki

doi:10.1007/s11164-019-03976-0

Cited by 2 publications

(2 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, Rac1 protein was found to be linked to the translocation of facilitated glucose transporter (GLUT4) in the muscle of diabetic patients 108 . Evidence for the participation of Rac1 in glucose uptake signalling in skeletal muscle has emerged from studies conducted on cell cultures and genetically engineered mice 109 . Actually, muscle‐specific Rac1 knockout mice displayed decreased glucose tolerance, and plasma insulin concentrations following glucose injection were higher in muscle‐specific rac1 knockout mice.…”

Section: Discussionmentioning

confidence: 99%

“…108 Evidence for the participation of Rac1 in glucose uptake signalling in skeletal muscle has emerged from studies conducted on cell cultures and genetically engineered mice. 109 Actually, muscle-specific Rac1 knockout mice displayed decreased glucose tolerance, and plasma insulin concentrations following glucose injection were higher in muscle-specific rac1 knockout mice. Moreover, the activation of the serine/threonine kinase PAK, an effector of Rac1, was impaired in insulin-resistant human and mouse skeletal muscle.…”

Section: Mechanisms By Which the Rac1 Gene Polymorphisms May Contribu...mentioning

confidence: 99%

See 1 more Smart Citation

Association between RAC1 gene variation, redox homeostasis and type 2 diabetes mellitus

Azarova

Klyosova

Полоников

2022

Eur J Clin Investigation

View full text Add to dashboard Cite

Background Increased production of reactive oxygen species (ROS) and oxidative stress are known to play a key role in the pathogenesis of type 2 diabetes (T2D); however, the relationship between genes encoding a multi‐subunit ROS‐generated enzyme NADPH oxidase and disease susceptibility remains unexplored. Aims The present pilot study investigated whether single‐nucleotide polymorphisms (SNP) at the RAC1 gene (Rac family small GTPase 1), a molecular switcher of NADPH oxidase, are associated with the risk of T2D, glucose metabolism and redox homeostasis. Materials & Methods DNA samples from 3206 unrelated Russian subjects (1579 T2D patients and 1627 controls) were genotyped for six common SNPs rs4724800, rs7784465, rs10951982, rs10238136, rs836478 and rs9374 of RAC1 using the MassArray‐4 system. Results SNP rs7784465 was associated with an increased risk of T2D (p = .0003), and significant differences in the RAC1 haplotypes occurred between the cases and controls (p = .005). Seventeen combinations of RAC1 genotypes showed significant associations with T2D risk (FDR <0.05). Associations of RAC1 polymorphisms with T2D were modified by environmental factors such as sedentary lifestyle, psychological stresses, a dietary deficit of fresh fruits/vegetables and increased carbohydrate intake. RAC1 polymorphisms were associated with biochemical parameters in diabetics: rs7784465 (p = .015) and rs836478 (p = .028) with increased glycated haemoglobin, rs836478 (p = .005) with increased fasting blood glucose, oxidized glutathione (p = .012) and uric acid (p = .034). Haplotype rs4724800A–rs7784465C–rs10951982G–rs10238136A–rs836478C–rs9374G was strongly associated with increased levels of hydrogen peroxide (p < .0001). Conclusion Thus, polymorphisms in the RAC1 gene represent novel genetic markers of type 2 diabetes, and their link with glucose metabolism and disease pathogenesis is associated with the changes in redox homeostasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Mechanisms By Which the Rac1 Gene Polymorphisms May Contribu...mentioning

confidence: 99%

Association between RAC1 gene variation, redox homeostasis and type 2 diabetes mellitus

Azarova

Klyosova

Полоников

2022

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

The interactions of CAP and LYN with the insulin signaling transducer CBL play an important role in polycystic ovary syndrome

Shen

et al. 2022

Metabolism

View full text Add to dashboard Cite

A critical role for the small GTPase Rac1 in insulin signaling that regulates glucose uptake in skeletal muscle

Cited by 2 publications

References 40 publications

Association between RAC1 gene variation, redox homeostasis and type 2 diabetes mellitus

Association between RAC1 gene variation, redox homeostasis and type 2 diabetes mellitus

The interactions of CAP and LYN with the insulin signaling transducer CBL play an important role in polycystic ovary syndrome

Contact Info

Product

Resources

About