Insulin Stimulated-Glucose Transporter Glut 4 Is Expressed in the Retina

Abstract

The vertebrate retina is a very metabolically active tissue whose energy demands are normally met through the uptake of glucose and oxygen. Glucose metabolism in this tissue relies upon adequate glucose delivery from the systemic circulation. Therefore, glucose transport depends on the expression of glucose transporters. Here, we show retinal expression of the Glut 4 glucose transporter in frog and rat retinas. Immunohistochemistry and in situ hybridization studies showed Glut 4 expression in the three nuclear layers of the retina: the photoreceptor, inner nuclear and ganglionar cell layers. In the rat retina immunoprecipitation and Western blot analysis revealed a protein with an apparent molecular mass of 45 kDa. 14C-glucose accumulation by isolated rat retinas was significantly enhanced by physiological concentrations of insulin, an effect blocked by inhibitors of phosphatidyl-inositol 3-kinase (PI3K), a key enzyme in the insulin-signaling pathway in other tissues. Also, we observed an increase in 3H-cytochalasin binding sites in the presence of insulin, suggesting an increase in transporter recruitment at the cell surface. Besides, insulin induced phosphorylation of Akt, an effect also blocked by PI3K inhibition. Expression of Glut 4 was not modified in retinas of a type 1 diabetic rat model. To our knowledge, our results provide the first evidence of Glut4 expression in the retina, suggesting it as an insulin- responsive tissue.

Rod phototransduction and light signal transmission during type 2 diabetes

“…While our experiments did not identify the mechanisms by which light-evoked photoreceptor responses are increased in the presence of additional glucose, likely targets include energy dependent processes in photoreceptors such as Na + /K + ATPases, Na + /Ca 2+ /K + exchangers and Ca 2+ ATPases (42), ATP-sensitive K + channels expressed in photoreceptors (43) or other ATP-dependent processes. The main glucose transporters expressed in photoreceptors are the insulin-independent GLUT-1 and insulin-dependent GLUT-4 (42), which have previously been reported to be reduced in diabetes (31; 44; 45), thus potentially explaining the inability of the photoreceptors in db/db mice to utilize increased glucose concentrations to promote their light responses. However, these findings are not universal and increased expression of GLUT-1 in diabetes has also been reported (39).…”

Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease

“…Similar to the heart, these changes indicate a decrease in metabolic flexibility. In the retina, glucose uptake occurs via both insulin-independent glucose transporter 1 (GLUT1) and insulin-dependent glucose transporter 4 (GLUT4) [ 102 , 103 ]. The retina also expresses a lipid sensor known as free fatty acid receptor 1 (Ffar1) ( Figure 3 ) [ 92 ].…”

Genetic variability in sodium-glucose cotransporter 2 influences glycemic control and risk for diabetic retinopathy in type 2 diabetes patients

“…It has been also show that glucose entry into pericytes increased twofold under hyperglycemia conditions (26). Such alterations in glucose supply could potentially change retinal energy metabolism and therefor result in complications (27).…”