Abstract
Severe hypoglycemia (below 35 mg/dL) appears most often in diabetes patients who continuously inject insulin. To rapidly cease the hypoglycemic state in this study, glucose reperfusion was conducted, which can induce a secondary neuronal death cascade following hypoglycemia. Acid sphingomyelinase (ASMase) hydrolyzes sphingomyelin into ceramide and phosphorylcholine. ASMase activity can be influenced by cations, pH, redox, lipids, and other proteins in the cells, and there are many changes in these factors in hypoglycemia. Thus, we expect that ASMase is activated excessively after hypoglycemia. Ceramide is known to cause free radical production, excessive inflammation, calcium dysregulation, and lysosomal injury, resulting in apoptosis and the necrosis of neurons. Imipramine is mainly used in the treatment of depression and certain anxiety disorders, and it is particularly known as an ASMase inhibitor. We hypothesized that imipramine could decrease hippocampal neuronal death by reducing ceramide via the inhibition of ASMase after hypoglycemia. In the present study, we confirmed that the administration of imipramine significantly reduced hypoglycemia-induced neuronal death and improved cognitive function. Therefore, we suggest that imipramine may be a promising therapeutic tool for preventing hypoglycemia-induced neuronal death.
Highlights
We have demonstrated that abrupt changes in blood glucose concentrations can cause the disturbance of several cellular programs that promote neuronal death, lead to the destruction of the blood–brain barrier (BBB), enhance the production of reactive oxygen species (ROS), and cause excessive zinc release and inflammation known to be mediated by the overactivation of microglia [9,10,11,12]
In the group administered imipramine for 7 days after hypoglycemia, Acid sphingomyelinase (ASMase) activation and ceramide production were greatly reduced (Figure 1A). In addition to this histological analysis, we measured changes in ASMase and neutral sphingomyelinase (NSMase) activity and analyzed the concentration of 11 major ceramide sub-species that are commonly observed in brain neurological disorders [49,50], such as within the hippocampus after hypoglycemia
We researched whether imipramine, an ASMase inhibitor, had neuroprotective effects on hypoglycemia-induced neuronal death
Summary
Type 1 and type 2 diabetes patients are routinely treated with insulin or insulin-releasing drugs in order to reduce their blood glucose levels. Many diabetes patients have experienced hypoglycemia while attempting to tightly control their blood glucose to prevent diabetic complications [2]. According to the Centers for Disease Control and Prevention (CDC), diabetic patients may experience low blood sugar as often as once or twice a week in the case of severe hypoglycemia (below 54 mg/dL). Devices that continuously monitor blood glucose levels and optimize the delivery of insulin or insulin-like drugs have been successful in treating diabetes. These approaches are not always successful in the complete prevention of hypoglycemia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
