SAT-283 Hypoglycemia Increases Expression Of The Epigenetic Regulator Lysine Specific Demethylase 1 In Humans

Abstract Disclosure: E. Caliskan Guzelce: None. A.E. Garza: None. R. Freeman: None. G.K. Adler: None. Objective: To determine the effect of insulin-induced hypoglycemia, with and without mineralocorticoid receptor (MR) blockade, on the expression of the epigenetic factor, lysine-specific demethylase-1 (LSD1). Research design: In a randomized crossover intervention, 17 healthy participants were pretreated with placebo or 100 mg eplerenone, followed by a hyper-insulinemic hypoglycemic clamp targeting a glucose of 2.8 mmol/l for 2 hours. Gene expression of LSD1 in peripheral blood mononuclear cells was assessed at baseline, during hypoglycemia and 4 hours post hypoglycemia. Results: LSD1 expression increased 2-fold at four hours post hypoglycemia versus baseline, p<0.04. MR antagonism prevented this increase, but did not alter the rise in ACTH, cortisol, aldosterone, epinephrine and glucagon. Conclusions: Hypoglycemia increases gene expression of LSD1 and this effect is blocked by an MR antagonism. Since LSD1 is an epigenetic regulator that affects numerous physiological and pathological processes, it is possible that hypoglycemia-induced changes in LSD1 could have long-term clinical consequences, such as progression of diabetic kidney disease. Presentation: Saturday, July 12, 2025