Introduction and Objective: Severe hypoglycemia can cause fatal arrhythmias, yet RH preconditioning reduces this risk (Reno et al. Diabetes 2017). We hypothesized that this protective effect in reducing arrhythmias is due to an RH preconditioning effect in improving cardiac mitochondrial function.Methods: Protocol 1: Adult male STZ-induced diabetic (D) rats were assigned to 3 days of recurrent insulin-induced hypoglycemia (DRH; 40-60 mg/dl for 60-90 min) or recurrent saline (DRS). Protocol 2: To distinguish 1) between hypoglycemia vs. insulin preconditioning per se, and 2) whether formoterol (β2-agonist that promotes mitochondrial biogenesis) could also improve respiration, diabetic rats were assigned to DRS, DRH, recurrent insulin plus glucose (DRI+G; glucose maintained > 100 mg/dl) or recurrent formoterol (DRF; 1 mg/kg/d). Seahorse respirometry analysis of isolated cardiac mitochondria was assessed on day 4.Results: In Protocol 1, DRH group had higher state 3 oxygen consumption rate (OCR) (DRS 191.2±4, DRH 228.6±14.2 pmol/min, P<0.05, t-test). In Protocol 2, DRH again demonstrated the greatest state 3 OCR (DRS 105.5±18.7, DRH 168.7±20.2, DRI+G 135.5±21.2; DRF 130.8±21.8 pmol/min; DRH vs. DRS, P=0.05, ANOVA).Conclusion: RH preconditioning enhanced cardiac mitochondrial function possibly explaining protective effects of RH against severe hypoglycemia-induced cardiac arrhythmias.
S. Velmurugan: None. H.J. Vekaria: None. L.A. Schoeder: None. A.M. Johnson: None. N.N. Nathoo: None. V. Gopal Viswanathan: None. P.G. Sullivan: None. S.J. Fisher: None.
Advancing Research Collaborations Award 2024 from Barnstable Brown Diabetes Center and Diabetes and Obesity Research Priority Area, University of Kentucky
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