Improvement of Vascular Insulin Sensitivity by Ranolazine.
Sol Guerra-Ojeda1, Adrian Jorda1,2, Constanza Aldasoro1
1Department of Physiology, University of Valencia, 46010 València, Spain.
International Journal of Molecular Sciences
|September 9, 2023
Summary
Ranolazine enhances insulin
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Endocrinology
Background:
- Ranolazine (RN) treats chronic coronary ischemia.
- Clinical trials suggest RN has anti-diabetic properties, lowering blood glucose and HbA1c.
- RN's effect on insulin sensitivity remains unclear.
Purpose of the Study:
- To investigate Ranolazine's potential to facilitate insulin's actions in the rabbit aorta.
- To understand the mechanisms behind RN's interaction with insulin signaling pathways.
Main Methods:
- Studied insulin-induced vasodilation and its relation to eNOS phosphorylation and NO formation.
- Examined RN's effect on insulin's vasodilator and vasoconstrictor modulation.
- Assessed the impact of combined RN and insulin on p-eNOS/eNOS and pAKT/AKT ratios.
Main Results:
- Insulin induced concentration-dependent vasodilation via eNOS phosphorylation and NO.
- RN potentiated all vasodilatory effects of insulin.
- RN facilitated insulin's ability to decrease adrenergic vasoconstriction.
- Combined RN and insulin significantly increased p-eNOS/eNOS and pAKT/AKT.
Conclusions:
- Ranolazine enhances both direct and indirect vasodilator effects of insulin.
- RN increases vascular sensitivity to insulin by reducing tissue resistance.
- This mechanism is crucial for understanding and potentially treating type II diabetes.
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