Abstract
It has been suggested that cells that are independent of insulin for glucose uptake, when exposed to high glucose or other nutrient concentrations, manifest enhanced mitochondrial substrate oxidation with consequent enhanced potential and generation of reactive oxygen species (ROS); a paradigm that could predispose to vascular complications of diabetes. Here we exposed bovine aortic endothelial (BAE) cells and human platelets to variable glucose and fatty acid concentrations. We then examined oxygen consumption and acidification rates using recently available technology in the form of an extracellular oxygen and proton flux analyzer. Acute or overnight exposure of confluent BAE cells to glucose concentrations from 5.5 to 25 mM did not enhance or change the rate of oxygen consumption (OCR) under basal conditions, during ATP synthesis, or under uncoupled conditions. Glucose also did not alter OCR in sub-confluent cells, in cells exposed to low serum, or in cells treated with added pyruvate. Likewise, overnight exposure to fatty acids of varying saturation had no such effects. Overnight exposure of BAE cells to low glucose concentration decreased maximal uncoupled respiration, but not basal or ATP related oxygen consumption. Labeled glucose oxidation to CO2 increased, but only marginally after high glucose exposure while oleate oxidation to CO2 decreased. Overnight exposure to linolenic acid, but not oleic or linoleic acid increased extracellular acidification consistent with enhanced glycolytic metabolism. We were unable to detect an increase in production of reactive oxygen species (ROS) from BAE cells exposed to high medium glucose. Like BAE cells, exposure of human platelets to glucose did not increase oxygen consumption. As opposed to BAE cells, platelet mitochondria demonstrate less respiratory reserve capacity (beyond that needed for basal metabolism). Our data do not support the concept that exposure to high glucose or fatty acids accelerates mitochondrial oxidative metabolism in endothelial cells or platelets.
Highlights
Some have suggested that high circulating glucose concentrations delivered to cells that are independent of insulin for glucose entry leads to increased substrate delivery to mitochondria
Hyperglycemia is critical to the development of the microvascular complications of type 1 and type 2 diabetes and, at least in subgroups, to macrovascular complications as well [23,24]
The authors reported increased H2O2 production in bovine and aortic endothelial (BAE) cells exposed to high glucose in the medium and asserted that the increased reactive oxygen species (ROS) was due to glucose-driven increased mitochondrial substrate oxidation
Summary
Some have suggested that high circulating glucose concentrations delivered to cells that are independent of insulin for glucose entry leads to increased substrate delivery to mitochondria. We examined the effect of acute glucose on mitochondrial oxidation in freshly isolated platelets obtained from non-diabetic and hyperglycemic, type 1 diabetic human subjects Both endothelial cells and platelets are independent of insulin for glucose uptake and, potentially vulnerable to excess substrate delivery when exposed to high medium nutrient composition. Both cell/particle types are important in mediating the effects of glycemia on vascular function [11,12] and abnormal endothelial function is a well-established risk factor for the macrovascular complications of diabetes [13]
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