Comparison of Glucose Influx and Blood Flow in Retina and Brain of Diabetic Rats

Abstract

Summary:Diabetes is associated with extensive microvascular pathology and decreased expression of the glucose transporter (GLUT-1) in retina, but not brain. To explore the basis of these differences, the authors simultaneously measured glucose influx (mol · g −1 · min) and blood flow (mL · g −1 · min −1 ) in retina and brain cortex of nondiabetic control rats (normoglycemic and acute-hyperglycemic) and in rats with streptozotocin-induced diabetes (with or without aminoguanidine (AMG) treatment) using a single-pass, dual-label indicator method. In addition, tissue glucose and adenosine triphosphate (nmol/mg dry weight) levels were measured. Glucose influx in retina exceeded that of cortex by about threefold for both the nondiabetic and diabetic groups. In contrast, blood flow in retina was significantly lower than in cortex by about threefold for each group. Retinal and cortical glucose influx in the diabetic rats was lower than in the nondiabetic acute-hyperglycemic group, but not in the normoglycemic group. Blood flow in these tissues remained relatively unchanged with glycemic conditions. The glucose levels in the diabetic retina (aminoguanidine untreated and aminoguanidine treated) were fourfold to sixfold greater than the nondiabetic retina. The cortical glucose levels remained unchanged in all groups. These data suggest that the accumulation of glucose in the diabetic retina cannot be explained by increased endothelialglucose uptake or increased vascular membrane permeability.

In Situ Mouse Carotid Perfusion Model: Glucose and Cholesterol Transport in the Eye and Brain

“…The D-glucose K m at the BBB is between 2 and 11 mmol/L (Puchowicz et al, 2004), which agrees with our finding. However, a previous in situ mouse brain perfusion study found a higher K m (B17 mmol/L) (Dagenais et al, 2000).…”

“…Some studies suggest that the eye V max is higher than that for the brain because there is more GLUT1 in the rat retinal capillaries than in the rat brain capillaries (Badr et al, 2000). An in vivo rat study that measured glucose influx into both the brain and retina using a blood glucose concentration of 2 to 32 mmol/L, confirms that the glucose influx obeys MichaelisMenten kinetics at the brain but not at the retina (Puchowicz et al, 2004). This observation for the retina agrees with our finding, because the glucose influx rate is proportional and linear when the glucose concentration is below or close to the K m value.…”

Sleep-Related Brain Activation Does Not Increase the Permeability of the Blood-Brain Barrier to Glucose

“…The backflux error is proportional to CBF and the duration of the experiment and is inversely proportional to the brainblood partition coefficient for the indicator. (Harik et al, 1994;Puchowicz et al, 2004).…”

“…Three samples (5 mL each) of the prevalently venous blood that dripped from the foramen magnum were collected to estimate radioactivity (liquid b-scintillator, LS 6500, Beckman, Fullerton, CA, USA) in the cerebral intravascular space (Harik et al, 1994;Puchowicz et al, 2004). Aliquots of the withdrawn arterial blood were taken for radioactivity measurement.…”

Inner Blood-Retinal Barrier Transporters: Relevance to Diabetic Retinopathy

“…In particular, D-mannitol, a representative nonpermeable paracellular marker, exhibits very low blood-to-retina influx permeability while D-glucose and amino acids, the substrates of membrane transporter molecules, exhibit over a 300-fold higher permeability than that of D-mannitol (Puchowicz et al, 2004;). These pieces of evidence strongly suggest that the inner BRB is a selective barrier for the retina.…”