OBJECTIVE-We examined whether ingestion of mediumchain triglycerides could improve cognition during hypoglycemia in subjects with intensively treated type 1 diabetes and assessed potential underlying mechanisms by testing the effect of ␤-hydroxybutyrate and octanoate on rat hippocampal synaptic transmission during exposure to low glucose.RESEARCH DESIGN AND METHODS-A total of 11 intensively treated type 1 diabetic subjects participated in stepped hyperinsulinemic-(2 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) euglycemic-(glucose ϳ5.5 mmol/l) hypoglycemic (glucose ϳ2.8 mmol/l) clamp studies. During two separate sessions, they randomly received either medium-chain triglycerides or placebo drinks and performed a battery of cognitive tests. In vitro rat hippocampal slice preparations were used to assess the ability of ␤-hydroxybutyrate and octanoate to support neuronal activity when glucose levels are reduced.RESULTS-Hypoglycemia impaired cognitive performance in tests of verbal memory, digit symbol coding, digit span backwards, and map searching. Ingestion of medium-chain triglycerides reversed these effects. Medium-chain triglycerides also produced higher free fatty acids and ␤-hydroxybutyrate levels compared with placebo. However, the increase in catecholamines and symptoms during hypoglycemia was not altered. In hippocampal slices ␤-hydroxybutyrate supported synaptic transmission under low-glucose conditions, whereas octanoate could not. Nevertheless, octanoate improved the rate of recovery of synaptic function upon restoration of control glucose concentrations.CONCLUSIONS-Medium-chain triglyceride ingestion improves cognition without adversely affecting adrenergic or symptomatic responses to hypoglycemia in intensively treated type 1 diabetic subjects. Medium-chain triglycerides offer the therapeutic advantage of preserving brain function under hypoglycemic conditions without causing deleterious hyperglycemia. Diabetes

We failed to find amplification or rearrangement of the PTH gene but documented hypomethylation of the PTH promoter in tumor tissue. We found that PEPP1 cells support expression of a reporter gene containing regulatory sequences from the human PTH gene promoter. Therefore, this is the first report documenting ectopic PTH production by a tumor as the result of transactivation of the PTH gene. PEPP1 cells may be useful for future studies aimed at elucidating the details of PTH gene regulation.