Na+-dependent glucose uptake and collagen synthesis by cultured bovine retinal pericytes

Abstract

This study was performed to clarify the presence of sodium-dependent glucose uptake and its role in the synthesis of type IV and type VI collagen by cultured bovine retinal pericytes. The glucose uptake by retinal pericytes and retinal endothelial cells was measured using 3H-D-glucose in the presence or absence of sodium. Glucose uptake in the presence of sodium was twice as high as that observed in the presence of phlorizin and sodium or in the absence of sodium. Sodium-dependent glucose uptake was observed at different sodium concentrations, and its half-maximal stimulation occurred at 48 mM. These findings were not observed in retinal endothelial cells. Levels of type IV and type VI collagen produced by retinal pericytes were significantly increased at glucose concentrations higher than 20 mM. Phlorizin decreased both collagen synthesis and glucose consumption by retinal pericytes incubated with 30 mM of glucose to the levels observed with 5 mM of glucose. These data suggest that sodium-dependent glucose uptake is present in retinal pericytes and that excessive glucose entry into the cell is an important factor for overproduction of collagen. Phlorizin normalized the synthesis of type IV and type VI collagen with decreasing glucose consumption under high glucose conditions.

Sodium Glucose Cotransporter 2 (SGLT2) Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells

“…The cell surface area is reported to correlate with cellular contraction [ 40 ]. Our study revealed a glucose concentration-dependent change in mesangial cell surface area, as we reported in bovine retinal pericytes [ 4 ]. Moreover, AMG, which enters cells primarily through SGLT [ 41 ], induced cellular contraction.…”

“…The properties of SGLT2 and SGLT1, including the Km values for D-glucose and Na + among the human, rabbit, and rat isoforms, have been reported [ 8 ]. We reported that the Km value for the D-glucose transporter in rat mesangial cells and bovine retinal pericytes were 1.93 mM [ 3 ] and 2.8 mM [ 4 ], respectively. Moreover, we reported that bovine retinal endothelial cells, other than retinal pericytes and mesangial cells, do not perform sodium-dependent glucose uptake [ 4 ].…”

“…We reported that the Km value for the D-glucose transporter in rat mesangial cells and bovine retinal pericytes were 1.93 mM [ 3 ] and 2.8 mM [ 4 ], respectively. Moreover, we reported that bovine retinal endothelial cells, other than retinal pericytes and mesangial cells, do not perform sodium-dependent glucose uptake [ 4 ]. The properties and kinetics of the glucose transporter in rat mesangial cells were identical to those of SGLT2.…”

“…We reported that mesangial cells and pericytes possess facilitated glucose transporter 1 (GLUT1) and SGLT, through which glucose enters at a ratio of almost 1:1 [ 3 ]. By inhibiting glucose entry through SGLT2 using phlorizin, we demonstrated that the normalization of excess glucose uptake under high glucose conditions by phlorizin attenuated the overproduction of type IV collagen, which decreased the cellular growth in bovine retinal pericytes [ 4 , 5 ]. Moreover, we demonstrated glucose-dependent cellular contraction via SGLT2 in this study.…”

“…These isoforms differ with respect to their affinity for glucose, their transport capacity for glucose, and the ratio of concomitant Na + and glucose transport [ 7 – 9 ]. Rat mesangial cells and retinal pericytes had almost the same glucose Km values, which were high enough to suggest the expression of SGLT2 [ 3 , 4 ]. Galactose transport also differs between SGLT1 and SGLT2.…”