Hypoglycemia is a state of abnormally low blood glucose. Many patients who use insulin, primarily for the treatment of diabetes, experience multiple bouts of hypoglycemia, termed recurrent hypoglycemia (RH). Because RH impairs cognitive function and ability to appropriately respond to a subsequent episode of hypoglycemia, it is critical to develop treatments. One approach, which we have taken here, is to attempt to preserve neuronal fuel supply during a hypoglycemic episode. Medium-chain triglycerides are medium-chain fatty acid (MCT) esters of glycerol that can provide an alternative fuel source to the brain via ketones; the hippocampus is known to express transporters for ketones and to be able to metabolize them. Hence, pre-administration of MCT prior to times of hypoglycemia could possibly prevent the deleterious effects of RH if they are due to loss of fuel generically rather than to specific loss of glucose. We have used a previously established three-day rat model of RH, in which rats are made hypoglycemic on each of three consecutive days and show both cognitive effects and impaired responses to hypoglycemia on the 4th day. Here, we gave Sprague-Dawley rats MCT (i.p.) prior to each episode of hypoglycemia, followed by cognitive testing, removal of the brain and analysis of brain proteins of interest: transporters for glucose and ketones as well as additional markers suggested by our prior studies. During cognitive testing, in vivo microdialysis was used to obtain real-time measures of hippocampal glucose and lactate; previous work showed that RH markedly affected local hippocampal metabolism during testing
