INTRODUCTION: Anesthetic preconditioning protects cardiomyocytes from oxidative 
stress-induced injury, but it is ineffective in patients with diabetes mellitus. 
To address the role of hyperglycemia in the inability of diabetic individuals to 
be preconditioned, we used human cardiomyocytes differentiated from induced 
pluripotent stem cells generated from patients with or without type 2 diabetes 
mellitus (DM-iPSC- and N-iPSC-CMs, respectively) to investigate the efficacy of 
preconditioning in varying glucose conditions (5, 11, and 25 mM).
METHODS: Induced pluripotent stem cells were induced to generate cardiomyocytes 
by directed differentiation. For subsequent studies, cardiomyocytes were 
identified by genetic labeling with enhanced green fluorescent protein driven by 
a cardiac-specific promoter. Cell viability was analyzed by lactate 
dehydrogenase assay. Confocal microscopy was utilized to measure opening of the 
mitochondrial permeability transition pore and the mitochondrial adenosine 
5'-triphosphate-sensitive potassium channels.
RESULTS: Isoflurane (0.5 mM) preconditioning protected N-iPSC- and DM-iPSC-CMs 
from oxidative stress-induced lactate dehydrogenase release and mitochondrial 
permeability transition pore opening in 5 mM and 11 mM glucose. Isoflurane 
triggered mitochondrial adenosine-5'-triphosphate-sensitive potassium channel 
opening in N-iPSC-CMs in 5 mM and 11 mM glucose and in DM-iPSC-CMs in 5 mM 
glucose; 25 mM glucose disrupted anesthetic preconditioning-mediated protection 
in DM-iPSC- and N-iPSC-CMs.
CONCLUSIONS: The opening of mitochondrial adenosine 5'-triphosphate-sensitive 
potassium channels are disrupted in DM-iPSC-CMs in 11 mM and 25 mM glucose and 
in N-iPSC-CMs in 25 mM glucose. Cardiomyocytes derived from healthy donors and 
patients with a specific disease, such as diabetes in this study, open 
possibilities in studying genotype- and phenotype-related pathologies in a 
human-relevant model.