High glucose induces cell death and changes in insulin signaling in cultured hypertensive vascular smooth muscle cells of rat
Alterations of the vessel structure, which is mainly determined by smooth muscle cells through growth and/or cell death mechanisms, are characteristic of diabetes complications. Cellular survival, such as the inhibiting of apoptotic processes, and signaling molecule in insulin signaling pathway, both involve mitogens and protein kinases B. Mitogen- activated protein kinases, ERK 1/2, have also been proven to play a role in cellular activities and physiological processes. Protein kinases B, AKT has the role of apoptosis, cell proliferation, and glucose metabolism through insulin regulation. In this study, we examined the influence of high glucose on hypertensive vascular smooth muscle cells (HVSMCs) growth and death. We hypothesized that high glucose has a negative effect on insulin signaling by altering protein kinases such as ERK1/2 and AKT expression in HVSMCs. HVSMCs were treated with increase concentrations of glucose (5, 10, 20, and 40 mM) for time periods of 24, 48, and 72 hr and cell viability was assessed using trypan blue exclusion method, AKT, and ERK1/2 expression was detected using western blot analysis. The results obtained showed that viability of HVSMCs decreases in timely manner during 24, 48, and 72 hr exposure to high glucose concentrations. Similar results were obtained when normotensive cells are exposed to high glucose for similar time periods. Forty millimolar of glucose had the greatest effect on cell viability, AKT and ERK1/2 expression at 24 hr in HVSMCs, decreasing cell viability, 52%, 45%, and 45% respectively. The results also showed that insulin signaling was completely inhibited with 10 and 20 mM for 48 hr. In conclusion, high glucose promotes cell death possibly through AKT and ERK1/2 expression which may participate in the development of diabetic vasculopathy.
Crystal J Byrd,
"High glucose induces cell death and changes in insulin signaling in cultured hypertensive vascular smooth muscle cells of rat"
ETD Collection for Tennessee State University.