scholarly journals Type 2 Diabetes Alters Vascular Cannabinoid Receptor 1 Expression, Phosphorylation Status, and Vasorelaxation in Rat Aorta

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4948
Author(s):  
Enrique Sánchez-Pastor ◽  
Xóchitl Trujillo ◽  
Christian Ramos-Flores ◽  
Mónica Ríos-Silva ◽  
Felipa Andrade ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Rat Aorta ◽  
Cardiovascular Complications ◽  
Cb1 Receptor ◽  
Receptor Expression ◽  
Vasorelaxant Effect

Previous studies have suggested a role of the endocannabinoid system in metabolic diseases, such as diabetes. We investigated the effect of diabetes on cannabinoid receptor type 1 (CB1) expression and cannabinoid-induced vasorelaxation in rat aorta rings. Aortas from healthy rats and from rats with experimentally induced diabetes were used to compare the vasorelaxant effect of the cannabinoid agonist arachidonylcyclopropylamide (ACPA) and CB1 expression and localization. After 4–8 weeks of diabetes induction, CB1 receptor expression and CB1 phosphorylation were higher in aortic rings, in association with greater vasorelaxation induced by the CB1 agonist ACPA compared to healthy rats. The vasorelaxant effect observed in healthy rats is similar throughout the study. Further studies are needed to elucidate the implications of CB1 receptor overexpression in diabetes and its influence on the progression of the cardiovascular complications of this metabolic disease.

scholarly journals Role of endocannabinoid system in the pathogenesis of obesity: how can we help a patient? From theory to practice

2020 ◽  
Vol 4 (6) ◽  
pp. 382-389
Author(s):  
V.A. Dudareva ◽  
◽  
M.L. Maksimov ◽  
I.G. Djadikova ◽  
A.A. Zveginceva ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Medical Society ◽  
Cannabinoid Receptor 1 ◽  
Peripheral Tissues ◽  
Theory To Practice

Obesity that results in various metabolic disorders is one of the central concerns of modern healthcare system. Only 4% to 5% of patients with metabolic syndrome achieve favorable outcomes without any additional pharmacotherapy. Therefore, many patients require weight-loss drugs in addition to non-pharmacological treatments. The endocannabinoid system and the drugs that affect its functions receive a widespread attention of medical society due to its effects on behavioral and cerebral functions and its potential use as a therapeutic “target” in various peripheral and neurological psychiatric disorders. Among known to date cannabinoid receptors, type 1 receptors play a role in the development of obesity. It was demonstrated that the blockade of these receptors in the hypothalamus reduces appetite, inhibits adipocyte activation in peripheral tissues, prevents lipogenesis, and increases the level of adiponectin. The result is the decreased levels of atherogenic lipoproteins and improved insulin resistance. This article addresses the results of fundamental and clinical studies on Dietressa, a drug composed of affine-purified antibodies to cannabinoid receptor 1. Case report of a patient with obesity that analyzes pharmaceutical and non-pharmaceutical treatment approaches is described.KEYWORDS: obesity, metabolic syndrome, diet, endocannabinoid system, cannabinoids, cannabinoid receptors, affine-purified antibodies.FOR CITATION: Dudareva V.A., Maksimov M.L., Djadikova I.G. et al. Role of endocannabinoid system in the pathogenesis of obesity: how can we help a patient? From theory to practice. Russian Medical Inquiry. 2020;4(6):382–389. DOI: 10.32364/2587-6821-2020-4-6-382-389.

scholarly journals Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 708 ◽  
Author(s):  
Valeria Tutino ◽  
Maria Gabriella Caruso ◽  
Valentina De Nunzio ◽  
Dionigi Lorusso ◽  
Nicola Veronese ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Normal Mucosa ◽  
Cb1 Receptor ◽  
Receptor Expression ◽  
Altered Expression ◽  
Downstream Signaling ◽  
Metastatic Process

Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.

scholarly journals On the Role of Central Type-1 Cannabinoid Receptor Gene Regulation in Food Intake and Eating Behaviors

2021 ◽  
Vol 22 (1) ◽  
pp. 398
Author(s):  
Mariangela Pucci ◽  
Elizabeta Zaplatic ◽  
Maria Vittoria Micioni Di Bonaventura ◽  
Emanuela Micioni Di Bonaventura ◽  
Paolo De Cristofaro ◽  
...  
Keyword(s):  
Food Intake ◽  
Eating Behaviors ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Receptor Gene ◽  
Endocannabinoid System ◽  
Central Type ◽  
Type 1 Cannabinoid Receptor

Different neuromodulatory systems are involved in long-term energy balance and body weight and, among these, evidence shows that the endocannabinoid system, in particular the activation of type-1 cannabinoid receptor, plays a key role. We here review current literature focusing on the role of the gene encoding type-1 cannabinoid receptors in the CNS and on the modulation of its expression by food intake and specific eating behaviors. We point out the importance to further investigate how environmental cues might have a role in the development of obesity as well as eating disorders through the transcriptional regulation of this gene in order to prevent or to treat these pathologies.

The cloning and characterization of the cannabinoid type 1 receptor

2018 ◽  
Author(s):  
Mary E. Abood ◽  
Thomas Gamage
Keyword(s):  
Chronic Pain ◽  
Cannabinoid Receptor ◽  
Functional Characterization ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Cannabinoid Type 1 Receptor ◽  
Endogenous Cannabinoid ◽  
Endogenous Cannabinoid System

The cloning and characterization of the first cannabinoid receptor (now known as the cannabinoid type 1 (CB1) receptor) by Matsuda et al. in the landmark paper discussed in this chapter was a seminal discovery in 1990. While the analgesic properties of marijuana had been known for thousands of years, the mechanisms through which marijuana produces analgesia were not understood. The identification and functional characterization of the CB1 receptor led to the discovery of an endogenous cannabinoid system (the endocannabinoid system), which has now been shown to be important not only for acute and chronic pain states, but also for a whole host of physiological and pathophysiological disorders.

scholarly journals Endocannabinoidome and its role in neurological disorders-A comprehensive update of existing literature

2021 ◽  
Vol 5 (1) ◽  
pp. 034-047
Author(s):  
Rajib Dutta
Keyword(s):  
Neurological Disorders ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 2 ◽  
Medical Benefits ◽  
Related Compounds

Medical benefits of cannabis and related compounds is widely known. Discovery of psychotropic plant cannabinoid Δ9-tetrahydrocannabinol have urged researchers to study more about the cannabinoid system and related therapeutics in the field of neurology and medicine. Where activation of cannabinoid receptor type 1 (CB1R) yielded in unwanted and serious side effects, discovery of cannabinoid receptor type 2 (CB2R) and its ligands gave a new hope. Till now there is limited success in this field because of complex expanded endocannabinoid system comprising of receptors, ligands and enzymes. In this review we will update about the role of endocannabinoidome relevant to neurological disorders.

Role of angiotensin-converting enzyme 2 (ACE2) in diabetic cardiovascular complications

2013 ◽  
Vol 126 (7) ◽  
pp. 471-482 ◽  
Author(s):  
Vaibhav B. Patel ◽  
Nirmal Parajuli ◽  
Gavin Y. Oudit
Keyword(s):  
Diabetes Mellitus ◽  
Angiotensin Converting Enzyme ◽  
Vascular Function ◽  
Systolic Dysfunction ◽  
Cardiovascular Complications ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Obesity And Diabetes

Diabetes mellitus results in severe cardiovascular complications, and heart disease and failure remain the major causes of death in patients with diabetes. Given the increasing global tide of obesity and diabetes, the clinical burden of diabetes-induced cardiovascular disease is reaching epidemic proportions. Therefore urgent actions are needed to stem the tide of diabetes which entails new prevention and treatment tools. Clinical and pharmacological studies have demonstrated that AngII (angiotensin II), the major effector peptide of the RAS (renin–angiotensin system), is a critical promoter of insulin resistance and diabetes mellitus. The role of RAS and AngII has been implicated in the progression of diabetic cardiovascular complications and AT1R (AngII type 1 receptor) blockers and ACE (angiotensin-converting enzyme) inhibitors have shown clinical benefits. ACE2, the recently discovered homologue of ACE, is a monocarboxypeptidase which converts AngII into Ang-(1–7) [angiotensin-(1–7)] which, by virtue of its actions on the MasR (Mas receptor), opposes the effects of AngII. In animal models of diabetes, an early increase in ACE2 expression and activity occurs, whereas ACE2 mRNA and protein levels have been found to decrease in older STZ (streptozotocin)-induced diabetic rats. Using the Akita mouse model of Type 1 diabetes, we have recently shown that loss of ACE2 disrupts the balance of the RAS in a diabetic state and leads to AngII/AT1R-dependent systolic dysfunction and impaired vascular function. In the present review, we will discuss the role of the RAS in the pathophysiology and treatment of diabetes and its complications with particular emphasis on potential benefits of the ACE2/Ang-(1–7)/MasR axis activation.

scholarly journals The role of selected mechanisms of innate immunity in the pathogenesis of diabetes

2021 ◽  
Vol 11 (9) ◽  
pp. 544-549
Author(s):  
Paulina Trojanowska ◽  
Magdalena Chrościńska-Krawczyk ◽  
Alina Trojanowska ◽  
Ewa Tywanek ◽  
Jakub Wronecki ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
The Body ◽  
Low Grade ◽  
Intracellular Space ◽  
Cytoplasmic Proteins

Understanding the important role of the non-specific immune response in protecting the body against the development of numerous diseases has become partially possible after the discovery of several classes of pattern recognition receptors (PRR), such as Toll-like or NOD-like receptors. A group of cytoplasmic proteins called the inflammasome, which detect PAMP and DAMP through the PRR receptors, is able to activate pro-inflammatory cytokines and trigger an acute inflammatory reaction both in the extracellular and intracellular space. Low-grade systemic and local inflammation contributes to the development and progression of various conditions, including autoimmune and metabolic diseases, such as diabetes, metabolic syndrome and atherosclerosis, which until recently were not even considered inflammatory diseases. This review will discuss the role of innate immunity in the development of type 1 and type 2 diabetes, focusing on the role of specific innate immunity receptors and insulin resistance involved in these diseases pathogenesis.

scholarly journals A Protective Role of Arecoline Hydrobromide in Experimentally Induced Male Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Indraneel Saha ◽  
Joydeep Das ◽  
Biswaranjan Maiti ◽  
Urmi Chatterji
Keyword(s):  
Glucose Transporter ◽  
Serum Insulin ◽  
Diabetic Rats ◽  
Receptor Expression ◽  
Cell Regeneration ◽  
Sialic Acid Content ◽  
Glucose Transporter 2 ◽  
Experimentally Induced

Objectives.Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats.Methods.Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed.Results.Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitatedβ-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related toβ-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1) and glucose transporter 2 (GLUT-2), were found to be activated by arecoline at the protein level.Conclusion.It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes.

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