Q2. What is the role of sitagliptin in the prevention of diabetes?
It inhibits dipeptidyl peptidase-4(DPP-4), the enzyme responsible for inactivating the incretin hormone glucagon-like peptide-1 (GLP1), and sitagliptin is reported to be cardioprotective in a rat model with type 2 diabetes through maintaining endogenous GLP-1 levels74.
Q3. What is the role of antimycin in the generation of ROS?
Antimycin mediates uncoupling of the ETC via dissipation of the H+ electrochemical gradientand this has been associated with an increase in ROS synthesis24.
Q4. What is the role of xanthine oxidase in the patho?
Elevated uric acid has been demonstrated as a biomarker for mortality and requirement forcardiac transplantation in heart failure patients35, so inhibition of xanthine oxidase may have beneficial outcomes in these individuals.
Q5. What is the role of the anti-oxidant in the treatment of diabetic cardiomyopathy?
well-tolerated systemic anti-oxidants such as curcumin, which have multiple beneficial effects and are well tolerated, may prove to be useful in reducing oxidative stress in diabetic cardiomyopathy.
Q6. What is the role of nobiletin in diabetic cardiomyopathy?
In addition, analysis of mRNA expression of NADPH oxidase subunits in cardiac tissue showed that nobiletin-treated diabetic mice had significant reductions in p22phox and gp91phox compared to the control diabetic mice, which may account for the lower levels of the lipid peroxidation marker malondialdehyde (MDA) with nobiletin administration.
Q7. What is the current status of coenzyme-Q10?
Coenzyme-Q10 is currently available as a non-prescription oral dietary supplement, and a recent randomised controlled trial indicated that its use as an adjunct therapy for chronic heart failure was associated with a significant reduction in major adverse cardiovascular events66.
Q8. What is the role of coenzyme-Q10 in cardiomyopathy?
Highly metabolic tissues such as the myocardium are abundant in mitochondria and therefore have high concentrations of coenzyme-Q10.
Q9. What is the role of AGE/RAGE in the synthesis of ROS?
It is hypothesised that AGE/RAGE-derived ROS can interact with NADPH oxidase enzymes to potentiate further ROS synthesis, and that NADPH oxidase-derived ROS can have the same effect on AGE/RAGE-derived ROS in a positive feedback loop45.
Q10. What is the recent study showing that the levels of glutathione peroxidas?
A recent study has demonstrated that levels of the anti-oxidant glutathione peroxidase 3 are reduced with age, accompanied by an increased risk of adverse cardiovascular events64 suggesting that preventing this decline or provision of exogenous anti-oxidants may be therapeutically beneficial.
Q11. What is the role of NOX2 in cardiac hypertrophy?
NOX2 has also been implicated in the induction of cardiac hypertrophy by the vasoconstrictive peptide angiotensin II through observations that small interference RNA (siRNA)induced knock down of NOX2 expression in cardiomyocytes abolished both angiotensin II-induced O2.
Q12. What is the role of oxidative stress in the development of diabetes mellitus?
Oxidative stress is believed to be involved in the pathogenesis of all of these conditions10 and this review will focus primarily on the role of enhanced ROS production in the development of diabetic cardiomyopathy.
Q13. What is the significance of the observation that transgenic mice overexpressing human GTPCH in their?
Of particular interest was the observation that transgenic mice overexpressing human GTPCH in their cardiomyocytes showed significantly attenuated diabetesinduced cardiac remodelling and they had improved calcium handling44.
Q14. What is the role of NOX4 in cardiomyocytes?
NOX1 and NOX3 are not expressed by mouse heart29 but studies have been performed to identify the role of the NOX4 isoform that is mainly expressed in the mitochondria of cardiomyocytes.
Q15. What is the role of xanthine oxidase inhibitors in cardio?
This suggests that inhibition of uric acid production has therapeutic potential in this subset of dilated cardiomyopathy patients, but further investigation is warranted to ascertain the precise mechanism(s) of action and therapeutic benefit of xanthine oxidase inhibitors in humans.
Q16. What is the role of rac1 in the regulation of myocardial redox?
Studies have been designed to determine whether exercise training affects the expression ofNADPH oxidase regulatory subunits, and whether this modifies myocardial redox status.
Q17. What is the way to prevent the reduction of GTPCH activity in diabetes?
identifying the factors responsible for reductions in GTPCH activity in diabetes and selectively preventing this from occurring in the heart is unlikely to be therapeutically feasible, so a more practicable approach may be through elevating BH4 levels to compensate for the reductions in GTPCH.
Q18. What is the role of sitagliptin in the prevention of diabetic cardiomyopathy?
There are no reports of use of DPP-4 inhibitors such as sitagliptin being associated with reductions in cardiac hypertrophy in humans, and further studies are required to determine whether they may have a role in the prevention or treatment of diabetic cardiomyopathy.