Insulin-independent GLUT4 translocation in proliferative vascular smooth muscle cells involves SM22α.

Abstract

The insulin-sensitive glucose transporter 4 (GLUT4) is a predominant facilitative glucose transporter in vascular smooth muscle cells (VSMCs) and is significantly upregulated in rabbit neointima. This study investigated the role of GLUT4 in VSMC proliferation, the cellular mechanism underlying PDGF-BB-stimulated GLUT4 translocation, and effects of SM22α, an actin-binding protein, on this process. Chronic treatment of VSMCs with PDGF-BB significantly elevated GLUT4 expression and glucose uptake. PDGF-BB-induced VSMC proliferation was dependent on GLUT4-mediated glucose uptake. Meanwhile, the response of GLUT4 to insulin decreased in PDGF-BB-stimulated VSMCs. PDGF-BB-induced GLUT4 translocation partially rescued glucose utilization in insulin-resistant cells. Immunofluorescence and western blot analysis revealed that PDGF-BB induced GLUT4 translocation in an actin dynamics-dependent manner. SM22α disruption facilitated GLUT4 translocation and glucose uptake by promoting actin dynamics and cortical actin polymerization. Similar results were observed in VSMCs of SM22α -/- mice. The in vivo experiments showed that the glucose level in the neointima induced by ligation was significantly increased in SM22α -/- mice, accompanied by increased neointimal thickness, compared with those in wild-type mice. These findings suggest that GLUT4-mediated glucose uptake is involved in VSMC proliferation, and provide a novel link between SM22α and glucose utilization in PDGF-BB-triggered proliferation.

KEY MESSAGES:

• GLUT4-mediated glucose uptake is required for the VSMC proliferation. • PDGF-BB-induced GLUT4 translocation partially rescues glucose uptake in insulin resistance. • SM22α disruption enhances PDGF-BB-induced GLUT4 translocation. • Glucose level in injured vascular tissue is positively correlated with neointimal hyperplasia.

• Authors: Li-Li Zhao, Fan Zhang, Peng Chen, Xiao-Li Xie, Yong-Qing Dou, Yan-Ling Lin, Lei Nie, Pin Lv, Dan-Dan Zhang, Xiao-Kun Li, Sui-Bing Miao, Ya-Juan Yin, Li-Hua Dong, Yu Song, Ya-Nan Shu, Mei Han
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 95 Issue 2 Pg. 181-192 (02 2017) ISSN: 1432-1440 [Electronic] Germany
• PMID: 27631639 (Publication Type: Journal Article)

Chemical References

• Actins
• Angiogenesis Inducing Agents
• DNA-Binding Proteins
• GLUT4 enhancer factor, mouse
• Insulin
• Microfilament Proteins
• Muscle Proteins
• Proto-Oncogene Proteins c-sis
• RNA, Small Interfering
• Tagln protein, mouse
• Transcription Factors
• Becaplermin
• Glucose

Topics

• Actins (metabolism)
• Angiogenesis Inducing Agents (pharmacology)
• Animals
• Aorta (metabolism)
• Becaplermin
• Carotid Artery Injuries (metabolism)
• Cell Proliferation (drug effects)
• Cells, Cultured
• DNA-Binding Proteins (drug effects, metabolism)
• Glucose (metabolism)
• Insulin (pharmacology)
• Insulin Resistance (physiology)
• Male
• Mice
• Microfilament Proteins (genetics, metabolism)
• Muscle Proteins (genetics, metabolism)
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Neointima (metabolism)
• Polymerization
• Proto-Oncogene Proteins c-sis (pharmacology)
• RNA, Small Interfering (genetics)
• Rats
• Rats, Sprague-Dawley
• Transcription Factors (drug effects, metabolism)