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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487645PMC
http://dx.doi.org/10.3390/ijms241713532DOI Listing

Publication Analysis

Top Keywords

insulin sensitivity
8
nitric oxide
8
facilitated vasodilator
8
vasodilator effects
8
effects
6
improvement vascular
4
vascular insulin
4
sensitivity ranolazine
4
ranolazine ranolazine
4
ranolazine drug
4

Similar Publications

In this study, two high-content flavonoid derivatives [3-8 biapigenin (HM 104) and quercetin-3--β--galactopyranoside (HM 111)] were obtained through the bioactivity-guided isolation of antidiabetic compounds from flowers. HM 104 and HM 111 exhibited good glucose consumption in fatty acid-induced insulin-resistant HepG2 cells. Moreover, both active compounds enhanced glucose uptake by restoring the expression of key regulators of glucose metabolism, including insulin receptor substrate 1, phosphoinositide 3-kinase, protein kinase B, and glucose transporter type 4, and by mitigating the expression of forkhead box O1 and the factors involved in gluconeogenesis.

View Article and Find Full Text PDF

The regulatory effect of breastfeeding on offspring metabolism has garnered significant attention as an effective strategy in combating childhood obesity. However, the underlying mechanism remains largely unknown. Through integrated analysis of multiple human milk peptide databases and functional screening, MDPAO1 (milk-derived peptide associated with obesity 1) was identified as having potential activity in promoting the expression of thermogenic genes.

View Article and Find Full Text PDF

NORAD exacerbates metabolic dysfunction-associated steatotic liver disease development via the miR-511-3p/Rock2 axis and inhibits ubiquitin-mediated degradation of ROCK2.

Metabolism

December 2024

Department of Pathology, School of Basic Medical Sciences, Wannan Medical College, Wuhu, China; Postdoctoral Research Station of Clinical Medicine, Jinan University, Guangzhou, China. Electronic address:

Background & Aims: Abnormal expression of long noncoding RNAs is strongly linked to metabolic dysfunction-associated steatotic liver disease (MASLD). However, the precise molecular mechanisms remain unclear. This study explores the roles of noncoding RNA activated by DNA damage (NORAD)/miR-511-3p/Rho-associated protein kinase 2 (Rock2) axis and the NORAD/ROCK2 interaction in the development of MASLD.

View Article and Find Full Text PDF

Maternal neonicotinoid pesticide exposure impairs glucose metabolism by deteriorating brown fat thermogenesis.

Ecotoxicol Environ Saf

December 2024

Nanjing Women and Children's Healthcare Institute, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China. Electronic address:

Background: Neonicotinoids (NEOs) are well-designed highly selective pesticides that target nicotinic acetylcholine receptors. However, their extensive use, accumulation, and biomagnification pose significant risks to humans. Increasing evidence has suggested that NEOs may affect glucose homeostasis, but little research has linked NEOs exposure to gestational diabetes mellitus (GDM), which is the most common disease in pregnancy.

View Article and Find Full Text PDF

The present study examined the relationships between trunk tissue distribution, metabolic risk factors, and physical performance in young Japanese individuals using cross-sectional and longitudinal analyses. Thirty-six healthy Japanese men (n = 20, body mass index [BMI]: 20.8 ± 2.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!