Diabetic patients are more susceptible to
myocardial ischemia damage than nondiabetic patients, with worse clinical outcomes and greater mortality. The mechanism may be related to
glucose metabolism, mitochondrial homeostasis, and oxidative stress.
Pyridostigmine may improve vagal activity to protect cardiac function in
cardiovascular diseases. Researchers have not determined whether
pyridostigmine regulates
glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice. In the present study, autonomic imbalance, myocardial damage,
mitochondrial dysfunction, and oxidative stress were exacerbated in
isoproterenol-stimulated diabetic mice, revealing the myocardial vulnerability of diabetic mice to injury compared with mice with diabetes or exposed to
isoproterenol alone. Compared with normal mice, the expression of
glucose transporters (GLUT)1/4
phosphofructokinase (PFK) FB3, and
pyruvate kinase isoform (PKM) was decreased in diabetic mice, but increased in
isoproterenol-stimulated normal mice. Following exposure to
isoproterenol, the expression of (GLUT)1/4
phosphofructokinase (PFK) FB3, and PKM decreased in diabetic mice compared with normal mice. The downregulation of
SIRT3/AMPK and IRS-1/Akt in
isoproterenol-stimulated diabetic mice was exacerbated compared with that in diabetic mice or
isoproterenol-stimulated normal mice.
Pyridostigmine improved vagus activity, increased GLUT1/4, PFKFB3, and PKM expression, and ameliorated
mitochondrial dysfunction and oxidative stress to reduce myocardial damage in
isoproterenol-stimulated diabetic mice. Based on these results, it was found that
pyridostigmine may reduce myocardial vulnerability to injury via the
SIRT3/AMPK and IRS-1/Akt pathways in diabetic mice with
isoproterenol-induced myocardial damage. This study may provide a potential therapeutic target for myocardial damage in diabetic patients.