“Δ9-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain.
The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain.
Low blood THC levels of <1 ng/ml corresponded to an increased glucose uptake while blood THC levels > 10 ng/ml coincided with a decreased glucose uptake. The effective concentration in this region was estimated 2.4 ng/ml.
This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose – an effect that may be of relevance in behavioural studies.”
https://www.ncbi.nlm.nih.gov/pubmed/28219717]]>
Category Archives: Diabetes
GPR55: a new promising target for metabolism?
“GPR55 is a G-protein coupled receptor (GPCR) that has been identified as a new cannabinoid receptor. Given the wide localization of GPR55 in brain and peripheral tissues, this receptor has emerged as a regulator of multiple biological actions. Lysophosphatidylinositol (LPI) is generally accepted as the endogenous ligand of GPR55. In this review, we will focus on the role of GPR55 in energy balance and glucose metabolism. We will summarize its actions on feeding, nutrient partitioning, gastrointestinal motility and insulin secretion in preclinical models and the scarce data available in humans. The potential of GPR55 to become a new pharmaceutical target to treat obesity and type 2 diabetes, as well as the foreseeing difficulties are also discussed.” https://www.ncbi.nlm.nih.gov/pubmed/28196832
“GPR55 – a putative “type 3” cannabinoid receptor in inflammation.” https://www.ncbi.nlm.nih.gov/pubmed/26669245
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The endocannabinoid system: no longer anonymous in the control of nitrergic signalling?
“The endocannabinoid system (ECS) is a key cellular signalling system that has been implicated in the regulation of diverse cellular functions. Importantly, growing evidence suggests that the biological actions of the ECS may, in part, be mediated through its ability to regulate the production and/or release of nitric oxide, a ubiquitous bioactive molecule, which functions as a versatile signalling intermediate. Herein, we review and discuss evidence pertaining to ECS-mediated regulation of nitric oxide production, as well as the involvement of reactive nitrogen species in regulating ECS-induced signal transduction by highlighting emerging work supporting nitrergic modulation of ECS function. Importantly, the studies outlined reveal that interactions between the ECS and nitrergic signalling systems can be both stimulatory and inhibitory in nature, depending on cellular context. Moreover, such crosstalk may act to maintain proper cell function, whereas abnormalities in either system can undermine cellular homoeostasis and contribute to various pathologies associated with their dysregulation. Consequently, future studies targeting these signalling systems may provide new insights into the potential role of the ECS -: nitric oxide signalling axis in disease development and/or lead to the identification of novel therapeutic targets for the treatment of nitrosative stress-related neurological, cardiovascular, and metabolic disorders.” https://www.ncbi.nlm.nih.gov/pubmed/28130308]]>
Developmental Role of Macrophage Cannabinoid-1 Receptor Signaling in Type-2 Diabetes.
“Islet inflammation promotes β-cell loss and type-2 diabetes (T2D), a process replicated in Zucker Diabetic Fatty (ZDF) rats in which β-cell loss has been linked to cannabinoid-1 receptor (CB1R)-induced pro-inflammatory signaling in macrophages infiltrating pancreatic islets. Here, we analyzed CB1R signaling in macrophages and its developmental role in T2Dα. ZDF rats with global deletion of CB1R are protected from β-cell loss, hyperglycemia and nephropathy present in ZDF littermates. Adoptive transfer of CB1R-/- bone marrow to ZDF rats also prevents β-cell loss and hyperglycemia, but not nephropathy. ZDF islets contain elevated levels of CB1R, IL-1β, TNF-α, the chemokine CCL2 and interferon regulatory factor-5 (IRF5), a marker of M1 inflammatory macrophage polarization. In primary cultured rodent and human macrophages, CB1R activation increased Irf5 expression, whereas knockdown of Irf5 blunted CB1R-induced secretion of inflammatory cytokines without affecting CCL2 expression, which was p38MAPKα-dependent. Macrophage-specific in vivo knockdown of Irf5 protected ZDF rats from β-cell loss and hyperglycemia. Thus, IRF5 is a crucial downstream mediator of diabetogenic CB1R signaling in macrophages and a potential therapeutic target.” https://www.ncbi.nlm.nih.gov/pubmed/28082458]]>
Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.
“The endocannabinoid signalling (ECS) system has been known to regulate glucose homeostasis.
Previous studies have suggested that the cannabinoid 2 (CB2) receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance.
Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-induced mice.
Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity.
Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.”
Medical Cannabis – another piece in the mosaic of autoimmunity?
“Legalization of cannabis’ medicinal use is rapidly increasing worldwide, raising the need to evaluate medical implications of cannabis. Currently evidence supports cannabis and its active ingredients as an immune-modulating agents, affecting T-cells, B-cells, Monocytes and Microglia-cells, causing an overall reduction in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokines. Due to the supporting evidence of cannabinoids as an immune-modulating agent, research focusing on cannabinoids and autoimmunity has emerged. Several clinical trials in multiple sclerosis, inflammatory bowel disease and fibromyalgia suggest cannabis’ effectiveness as an immune-modulator. However, contradicting results and lack of large scale clinical trials obscure these results. Though lacking clinical research, in-vitro and in-vivo experiments in rheumatoid arthritis, diabetes type 1 and systemic sclerosis, demonstrate a correlation between disease activity and cannabinoids.”
Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance.
“We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone.
CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity.
Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue.
CNR1 is upregulated in states of type 2 diabetes and insulin resistance.
Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis.
Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.”
Cannabis Use as Risk or Protection for Type 2 Diabetes: A Longitudinal Study of 18 000 Swedish Men and Women.
“Whether or not cannabis use may increase or decrease the risk of type 2 diabetes is not clear. We analyzed the association between cannabis and subsequent type 2 diabetes and if a potential positive or reverse association persisted after controlling for potential confounders.
In this population-based cohort study, 17,967 Swedish men and women (aged 18-84 years), who answered an extensive questionnaire in 2002 (including questions on cannabis use), were followed up for new cases of type 2 diabetes (n = 608) by questionnaire (in 2010) and in health registers during 2003-2011. Odds ratios (ORs) with 95% CIs were estimated in a multiple logistic regression analysis. Potential confounders included age, sex, BMI, physical inactivity, smoking, alcohol use, and occupational position.
Results. The crude association showed that cannabis users had a reduced risk of type 2 diabetes OR = 0.68 (95% CIs: 0.47-0.99). However, this inverse association attenuated to OR = 0.94 (95% CIs: 0.63-1.39) after adjusting for age.
Conclusions. The present study suggests that there is no association between cannabis use and subsequent type 2 diabetes after controlling for age. To make more robust conclusions prospective studies, with longer periods of follow-up and more detailed information about cannabis use, are needed.”
Experimental cannabidiol treatment reduces early pancreatic inflammation in type 1 diabetes.
“Destruction of the insulin-producing beta cells in type 1 diabetes (T1D) is induced by invasion of immune cells causing pancreatic inflammation.
Cannabidiol (CBD), a phytocannabinoid, derived from the plant, Cannabis sativa, was shown to lower the incidence of diabetes in non-obese diabetic (NOD) mice, an animal model of spontaneous T1D development.
The goal of this study was to investigate the impact of experimental CBD treatment on early pancreatic inflammation in T1D by intravital microscopy (IVM) in NOD mice.
CBD-treated NOD mice developed T1D later and showed significantly reduced leukocyte activation and increased FCD in the pancreatic microcirculation.
Experimental CBD treatment reduced markers of inflammation in the microcirculation of the pancreas studied by intravital microscopy.”
Marijuana Use and Type 2 Diabetes Mellitus: a Review.
“Marijuana is used by millions of people, with use likely to increase in the USA because of the trend towards increased decriminalization and legalization. Obesity and diabetes mellitus (DM) rates have increased dramatically in the USA over the past 30 years, with a recent estimate of 29 million individuals with DM. Because there is a plausible link between marijuana use and diabetes due to the known effects of cannabinoids on adipose tissue and glucose/insulin metabolism, it is important to study and understand how marijuana use is related to obesity and diabetes. This paper provides background on the human endocannabinoid system and studies of the association of marijuana use with body mass index/obesity, metabolic syndrome, prediabetes, and diabetes. The studies to date have shown that marijuana use is associated with either lower odds or no difference in the odds of diabetes than non-use.”