title: High-dose insulin inhibits gap junction intercellular communication in vascular smooth muscle cells.
abstract: Gap junction intercellular communication (GJIC) is important in mediating intercellular substance and signal transmission. Connexin (Cx)43 is a major component involved in GJIC in vascular tissue and its abnormal expression is closely associated with various vascular diseases. Insulin resistance is the central component of metabolic syndrome, and high doses of insulin can affect vascular function through multiple pathways, resulting in cardiovascular disease. However, the effects of insulin on GJIC function and connexin (Cx)43 expression in vascular smooth muscle cells (VSMCs) remain unclear. Following treatment of VSMCs with different doses of insulin, a fluorescence recovery after photobleaching (FRAP) assay was performed to evaluate GJIC function in treated VSMCs. The results showed that high‑dose insulin suppressed GJIC function. Western blot assays further demonstrated that high‑dose insulin induced the phosphorylation of Cx43 at s368 and downregulated the expression of Cx43. H2O2 release assays demonstrated that high‑dose insulin treatment significantly elevated the cellular H2O2 level. In addition, compared with cells treated with high‑dose insulin, pretreatment with catalase significantly restored the cellular GJIC function, decreased the phosphorylation level of Cx43 at s368, and enhanced Cx43 expression. In conclusion, these data indicate that high‑dose insulin inhibits cellular GJIC function through the oxidative stress‑activated signaling pathway. This phenomenon may also constitute a potential mechanism underlying the pathogenesis of insulin resistance and its complications.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ou
authors.initials: O
authors.lastname: Bian
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Haishan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Qigang
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Dingyin
authors.initials: D
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018031:Connexin 43; D007004:Hypoglycemic Agents; D007328:Insulin; D006861:Hydrogen Peroxide; D005947:Glucose