The anti-narcolepsy drug modafinil reverses hypoglycemia unawareness and normalizes glucose sensing of orexin neurons in male mice.

• DOI: 10.2337/figshare.21714221
• Publication Date: 2022-12-16T18:00:22Z
• Authors: Vishwendra Patel; Pallabi Sarkar; Dashiel M. Siegel; Suraj B. Teegala; Pamela R. Hirschberg; Hamad Wajid; Omar Itani; Vanessa H. Routh
• Keywords: Male; Neurons; 0301 basic medicine; Orexins; 0303 health sciences; Modafinil; Hypoglycemia; Diabetes Complications; Mice; 03 medical and health sciences; Glucose; Animals

<p> </p> <p>Perifornical hypothalamus (PFH) orexin glucose-inhibited (GI) neurons that facilitate arousal have been implicated in hypoglycemia awareness. Mice lacking exhibit narcolepsy and mediates the effect of anti-narcolepsy drug, modafinil. Thus, awareness may require a certain level for sympathetic symptoms (e.g., tremors, anxiety). Recurrent (RH) causes unawareness. We hypothesize RH impairs glucose sensitivity PFH orexin-GI modafinil normalizes these restores after RH. Using patch clamp recording, we found enhanced inhibition from male mice, thereby blunting activation low glucose. then used modified conditioned place preference (CPP) behavioral test to demonstrate reversed unawareness mice Similarly, restored normal neurons. conclude impaired plays role normalizing their is associated with restoration This suggests therapeutic target preventing unawareness.</p>