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Abnormal cannabidiol confers cardioprotection in diabetic rats independent of glycemic control.

ABSTRACT: Chronic GPR18 activation by its agonist abnormal cannabidiol (trans-4-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol; abn-cbd) improves myocardial redox status and function in healthy rats. Here, we investigated the ability of abn-cbd to alleviate diabetes-evoked cardiovascular pathology and the contribution of GPR18 to this effect. Four weeks after diabetes induction by streptozotocin (STZ, 55mg/kg; i.p), male Wistar rats received abn-cbd, the GPR18 antagonist (1,3-dimethoxy-5-methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-,cyclohexen-1-yl]benzene;O-1918), their combination (100µg/kg/day, i.p, each) or their vehicle for 2 weeks. Abn-cbd had no effect on diabetes-evoked cardiac hypertrophy or impaired glycemic control (hyperglycemia and hypoinsulinemia), but alleviated the associated reductions in left ventricular (LV) contractility (dP/dtmax) and relaxation (dP/dtmin) indices, and the increases in LV end diastolic pressure (LVEDP) and cardiac vagal dominance. Abn-cbd also reversed myocardial oxidative stress by restoring circulating and cardiac nitric oxide (NO) and adiponectin (ADN) levels and enhancing GPR18 expression and phosphorylation of Akt, ERK1/2 and eNOS in diabetic rats' hearts. Concurrent GPR18 blockade (O-1918) abrogated all favorable effects of abn-cbd in diabetic rats. Collectively, the current findings present evidence for abn-cbd alleviation of diabetes-evoked cardiovascular anomalies likely via GPR18 dependent restoration of cardiac adiponectin-Akt-eNOS signaling and the diminution of myocardial oxidative stress.

SUBMITTER: Matouk AI

PROVIDER: S-EPMC5767137 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Abnormal cannabidiol confers cardioprotection in diabetic rats independent of glycemic control.

Matouk Asmaa I AI Taye Ashraf A El-Moselhy Mohamed A MA Heeba Gehan H GH Abdel-Rahman Abdel A AA

European journal of pharmacology 20171220

Chronic GPR18 activation by its agonist abnormal cannabidiol (trans-4-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol; abn-cbd) improves myocardial redox status and function in healthy rats. Here, we investigated the ability of abn-cbd to alleviate diabetes-evoked cardiovascular pathology and the contribution of GPR18 to this effect. Four weeks after diabetes induction by streptozotocin (STZ, 55mg/kg; i.p), male Wistar rats received abn-cbd, the GPR18 antagonist (1,3-di ...[more]

PMID: 29274332

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Project description:Background:Diabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. This study aims to assess the level of glycemic control and factors contributing to uncontrolled glycemia among diabetic patients at the Nekemte Referral Hospital, West Ethiopia. Methods:A cross sectional study was conducted on diabetic patients attending the diabetes clinic of Nekemte Referral Hospital. A total of 252 study participants were included in the study. Data were collected by interviewing patients during hospital visits and reviewing respective databases. The association between dependent and independent variables was assessed using bivariable and stepwise multivariable logistic regression. A variable with a p-value < 0.05 was considered as an independent predictor. A patient's written informed consent was obtained after explaining the purpose and procedures of the study. Results:Mean age of the participants was 41.7 ± 17.6 years. The majority of the participants (67.1%) had poor knowledge about diabetes. The glycemic rate control was 40.5%; while more than half of the participants (59.5%) had poor glycemic control. On multivariable logistic analysis poor glycemic control was more likely to occur among unemployed (p < 0.001), patients with no family/social support (p = 0.024), duration of diabetes >10 years (p = 0.005), poor knowledge about diabetes (p = 0.012), taking insulin (p = 0.004) and taking metformin plus glibenclamide (p < 0.001). Conclusion:A finding of this study revealed that a glycemic control of study participants was poor. Thus greater effort is needed to improve glycemic control. Health care professionals should work on improving the adherence to anti-diabetic medications of diabetic patients and knowledge of diabetic patients on diabetes by providing education to the patients during follow up to improve glycemic control.

Project description:Diabetes mellitus and the associated complications represent a global burden on human health and economics. Cardiovascular diseases are the leading cause of death in diabetic patients, who have a 2-5 times higher risk of developing heart failure than age-matched non-diabetic patients, independent of other comorbidities. Diabetic cardiomyopathy is defined as the presence of abnormal cardiac structure and performance in the absence of other cardiac risk factors, such coronary artery disease, hypertension, and significant valvular disease. Hyperglycemia, hyperinsulinemia, and insulin resistance mediate the pathological remodeling of the heart, characterized by left ventricle concentric hypertrophy and perivascular and interstitial fibrosis leading to diastolic dysfunction. A change in the metabolic status, impaired calcium homeostasis and energy production, increased inflammation and oxidative stress, as well as an accumulation of advanced glycation end products are among the mechanisms implicated in the pathogenesis of diabetic cardiomyopathy. Despite a growing interest in the pathophysiology of diabetic cardiomyopathy, there are no specific guidelines for diagnosing patients or structuring a treatment strategy in clinical practice. Anti-hyperglycemic drugs are crucial in the management of diabetes by effectively reducing microvascular complications, preventing renal failure, retinopathy, and nerve damage. Interestingly, several drugs currently in use can improve cardiac health beyond their ability to control glycemia. GLP-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors have been shown to have a beneficial effect on the cardiovascular system through a direct effect on myocardium, beyond their ability to lower blood glucose levels. In recent years, great improvements have been made toward the possibility of modulating the expression of specific cardiac genes or non-coding RNAs in vivo for therapeutic purpose, opening up the possibility to regulate the expression of key players in the development/progression of diabetic cardiomyopathy. This review summarizes the pathogenesis of diabetic cardiomyopathy, with particular focus on structural and molecular abnormalities occurring during its progression, as well as both current and potential future therapies.

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Abnormal cannabidiol confers cardioprotection in diabetic rats independent of glycemic control.

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Abnormal cannabidiol confers cardioprotection in diabetic rats independent of glycemic control.

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