Improvement of Vascular Insulin Sensitivity by Ranolazine

Ranolazine (RN) is a drug used in the treatment of chronic coronary ischemia. Different clinical trials have shown that RN behaves as an anti-diabetic drug by lowering blood glucose and glycosylated hemoglobin (HbA1c) levels. However, RN has not been shown to improve insulin (IN) sensitivity. Our st...

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Published inInternational journal of molecular sciences Vol. 24; no. 17; p. 13532
Main Authors Guerra-Ojeda, Sol, Jorda, Adrian, Aldasoro, Constanza, Vila, Jose M., Valles, Soraya L., Arias-Mutis, Oscar J, Aldasoro, Martin
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.09.2023
MDPI
Subjects
Adrenergic receptors
adrenergic system
Angina pectoris
Blood sugar
Blood vessels
Cardiac arrhythmia
Care and treatment
Coronary vessels
Diabetes
Dilatation
Endothelium
Glucose
Glycosylated hemoglobin
Hemoglobin
Insulin
Ischemia
Metabolic syndrome
Nitric oxide
Ranolazine
Type 2 diabetes
vascular
Vasodilators
Spain
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Summary:Ranolazine (RN) is a drug used in the treatment of chronic coronary ischemia. Different clinical trials have shown that RN behaves as an anti-diabetic drug by lowering blood glucose and glycosylated hemoglobin (HbA1c) levels. However, RN has not been shown to improve insulin (IN) sensitivity. Our study investigates the possible facilitating effects of RN on the actions of IN in the rabbit aorta. IN induced vasodilation of the abdominal aorta in a concentration-dependent manner, and this dilatory effect was due to the phosphorylation of endothelial nitric oxide synthase (eNOS) and the formation of nitric oxide (NO). On the other hand, IN facilitated the vasodilator effects of acetylcholine but not the vasodilation induced by sodium nitroprusside. RN facilitated all the vasodilatory effects of IN. In addition, IN decreased the vasoconstrictor effects of adrenergic nerve stimulation and exogenous noradrenaline. Both effects were in turn facilitated by RN. The joint effect of RN with IN induced a significant increase in the ratio of p-eNOS/eNOS and pAKT/AKT. In conclusion, RN facilitated the vasodilator effects of IN, both direct and induced, on the adrenergic system. Therefore, RN increases vascular sensitivity to IN, thus decreasing tissue resistance to the hormone, a key mechanism in the development of type II diabetes.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241713532