Effects of insulin-induced acute hypoglycemia and normoglycemic hyperinsulinemia on the retinal uptake and ocular metabolism of glucose in rabbits

Glucose is the principal metabolic substrate for the retina in mammals, being essential for maintaining the functional activity of the retina; it can be supplied to the tissue by both vitreous humor and blood. Yet, the impact of hypoglycemia on retinal glucose metabolism has been poorly investigated. We have therefore studied the effects of acute insulin-induced hypoglycemia on the glucose uptake and metabolism in the retina, by analyzing the hypoglycemia-induced changes in the ocular distribution and metabolic fate of [3H]-2-deoxy-D-glucose (2-DG) and [14C]-D-glucose, both injected in the vitreous body. Rabbits were rendered hypoglycemic by subcutaneous injection of insulin (0.8 and 1.2 IU/kg). Insulin-induced hypoglycemia increased both retinal [3H]-radioactivity levels and retina to vitreous humor ratio of [3H]-radioactivity levels ([3H]-[R/VH]). Radio-chromatography showed that hypoglycemia did not induce any change in the retinal conversion of 2-DG to 2-DG-6-phosphate, but increased the conversion of [14C]-D-glucose to [14C]-lactate. Normoglycemic hyperinsulinemia caused no change in either retinal [3H]-radioactivity levels or [3H]-[R/VH] while decreasing retinal [14C]-radioactivity levels and retina to vitreous ratios of 14C-radioactivity levels. These results indicate that acute hypoglycemia increases the uptake rate of glucose by the retina and suggest that normoglycemic hyperinsulinemia may decrease retinal lactate, possibly stimulating its removal from the retina.