Periodic high extracellular glucose enhances production of collagens III and IV by mesangial cells

Abstract

We examined the effects of periodic changes in extracellular glucose concentration on matrix production and proliferation using three groups of cultured rat mesangial cells (MCs): 1) MCs in medium with continuous 5 mM glucose (CL), 2) MCs in medium alternating daily between 5 and 25 mM glucose (PH), and 3) MCs in medium with continuous 25 mM glucose (CH). MCs cultured in PH for 10 days produced 329 and 110% more type III collagen protein than MCs cultured in CL and CH, respectively. MCs cultured in PH induced 31 and 14% more type IV collagen than MCs cultured in CL and CH, respectively. Extracellular glucose concentration had no effect on the amount of type I collagen produced. MCs cultured in PH or CH for 5 days also expressed increased levels of type I, III, and IV collagen mRNA compared with MCs cultured in CL. MCs cultured in PH for 8-10 days also produced significantly more DNA than MCs in CL or CH. These data suggest that the temporal pattern of exposure to high extracellular glucose plays a role in regulating matrix formation and cellular proliferation by MCs. Furthermore, periodic elevations of extracellular glucose had a greater stimulatory effect on collagen production than a sustained elevation. These results suggest that decreasing the variability of blood glucose concentration may decrease the adverse effect of elevated glucose levels on MC matrix production and the progression of diabetic glomerulopathy.

Attenuated Superoxide Dismutase Induction in Retinal Cells in Response to Intermittent High Versus Continuous High Glucose

“…This concept is consistent with the findings that intermittent high glucose has been shown to lead to increased damage to the endothelial cells [4][5][6][7] , mesangial cells [8] and tubulointerstitial cells [9] in culture. Brownlee et al [10][11][12] have recently proposed a "unifying mechanism" by which all the pathways involved in the pathogenesis of diabetic complications are linked through a hyperglycemia-driven intracellular excess of reactive oxygen species (ROS), superoxide anion in particular.…”

“…We have shown previously that intermittent high glucose in endothelial cells results in increased markers of reactive species even when compared with continuous high glucose [5][6][7][8][9] . In this work we confirm in retinal pericytes and ARPE-19 cells that intermittent high glucose results in increased 3-NT and for the first time, that the levels of 3-NT adducted (nitrated) MnSOD increases in response to intermittent high as compared with high continuous glucose.…”

Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus

“…More recently it has been reported that specifically controlling post-prandial hyperglycaemia using a rapid-acting secretagogue (repaglinide) compared with glyburide resulted in a similar improvement of HbA 1c but was associated with a regression of carotid artery atherosclerosis [28]. In addition to these data, other clinical and experimental studies suggest that post-challenge hyperglycaemia or acute elevation of plasma glucose is deleterious for diverse functions related to atherogenesis [29][30][31][32][33][34][35][36][37][38][39]. Thus, the bulk of epidemiological, clinical and experimental evidence strongly suggests that efforts to monitor and control the common phenomenon of post-prandial hyperglycaemia should have uniquely beneficial effects on the chronic complications of type 2 diabetes.…”

Intermittent High Glucose Enhances Apoptosis Related to Oxidative Stress in Human Umbilical Vein Endothelial Cells

“…Cumulating in vitro evidence suggests that glucose variations may be more dangerous for the cells than stable high glucose. Mesangial cells that are cultured in periodic high glucose concentration increase matrix production more than cells that are cultured in high stable glucose (33). Similarly, fluctuations of glucose display a more dangerous effect than stable high glucose on tubulointerstitial cells, in terms of collagen synthesis and cell growth (34).…”