“Insulin resistance (IR) and obesity predispose diseases such as diabetes, cardiovascular and neurodegenerative disorders. Beta-caryophyllene (BCP), a natural sesquiterpene, exerts neuroprotective, anxiolytic and antidepressant effects via its selective agonism to cannabinoid receptor 2 (CB2R). BCP was shown to have an anti-diabetic effect, however, the implication of CB2R is yet to be elucidated. A link between CB2R agonism and PPAR-γ activation has been discussed, but the exact mechanism is not well-defined. This study was designed to examine the role of BCP in improving diet-induced metabolic (insulin resistance), neurobehavioral (anxiety, depression and memory deficit), and neurochemical (oxidative, inflammatory and neurotrophic factor) alterations in the prefrontal cortex of obese rats’ brain. The involvement of CB2R and/or PPAR-γ dependent activity was also investigated.
Category Archives: Diabetes
Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats.
“Diabetes and aging are risk factors for cognitive impairments after chronic cerebral hypoperfusion (CCH).
Cannabidiol (CBD) is a phytocannabinoid present in the Cannabis sativa plant. It has beneficial effects on both cerebral ischemic diseases and diabetes.
We have recently reported that diabetes interacted synergistically with aging to increase neuroinflammation and memory deficits in rats subjected to CCH.
The present study investigated whether CBD would alleviate cognitive decline and affect markers of inflammation and neuroplasticity in the hippocampus in middle-aged diabetic rats submitted to CCH.
These results suggest that the neuroprotective effects of CBD in middle-aged diabetic rats subjected to CCH are related to a reduction in neuroinflammation. However, they seemed to occur independently of hippocampal neuroplasticity changes.”
https://www.ncbi.nlm.nih.gov/pubmed/30430393
https://link.springer.com/article/10.1007%2Fs12640-018-9972-5
The protective effects of Δ9 -tetrahydrocannabinol against inflammation and oxidative stress in rat liver with fructose-induced hyperinsulinemia.
“A large amount of fructose is metabolized in the liver and causes hepatic functional damage. Δ9 -tetrahydrocannabinol (THC) is known as a therapeutic agent for clinical and experimental applications.
The study aims to investigate the effects of THC treatment on inflammation, lipid profiles and oxidative stress in rat liver with hyperinsulinemia.
According to the result, long-term and low-dose THC administration may reduce hyperinsulinemia and inflammation in rats to some extent.”
https://www.ncbi.nlm.nih.gov/pubmed/30427077 https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.13042]]>Beta-caryophyllene protects diet-induced dyslipidemia and vascular inflammation in rats: Involvement of CB2 and PPAR-γ receptors.
“Beta-caryophyllene (BCP) is a phytocannabinoid possessing selective agonistic activity to cannabinoid type-2 receptors (CB2R) and peroxisome proliferator-activated receptors-α (PPAR-α). However, few studies reported the contribution of PPAR-γ receptors in BCP effects. The aim of this study was to investigate the BCP effects on diet-induced dyslipidemia and vascular inflammation as well as the involvement of CB2R and PPAR-γ receptors. BCP treatment was superior to pioglitazone in anti-inflammatory and anti-atherosclerotic measures. BCP may represent a more potent alternate to pioglitazone avoiding its side effects in the treatment of insulin resistance and vascular inflammation.” https://www.ncbi.nlm.nih.gov/pubmed/30343038 https://www.sciencedirect.com/science/article/pii/S0009279718309347?via%3Dihub “β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934]]>
The relationship between cannabis use and diabetes: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III.
“The relationship between cannabis use and diabetes is puzzling. Although cannabis users versus non-users should theoretically have a higher likelihood of diabetes, epidemiological studies suggest otherwise. However, previous epidemiological studies have not considered the potential confounding effects of mental health disorders. As such, the relationship between cannabis use and diabetes was examined while accounting for a range of potential confounders, including mental health disorders.
RESULTS:
Although there was a considerable attenuation in the magnitude of the odds ratios after adjustment for confounders, there was still a decreased likelihood of diabetes for cannabis users versus non-users. The corresponding odds ratios of diabetes were 0.81 (95% confidence interval 0.70, 0.94) and 0.51 (95% confidence interval 0.41, 0.63) for lifetime and 12-month cannabis use, respectively.DISCUSSION AND CONCLUSIONS:
A decreased likelihood of diabetes for cannabis users versus non-users was indicated after accounting for a range of potential confounders, including mental health disorders. Before the protective effects of cannabis use for diabetes can be suggested, further epidemiological studies are needed that incorporate prospective designs, as well as feature innovative exposure measurements and statistical analyses.” https://www.ncbi.nlm.nih.gov/pubmed/30288813 https://onlinelibrary.wiley.com/doi/abs/10.1111/dar.12867]]>Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics.
“Targeting peripheral CB1R is desirable for the treatment of metabolic syndromes without adverse neuropsychiatric effects.
We previously reported a human hCB1b isoform that is selectively enriched in pancreatic beta-cells and hepatocytes, providing a potential peripheral therapeutic hCB1R target. It is unknown whether there are peripherally enriched mouse and rat CB1R (mCB1 and rCB1, respectively) isoforms.
In this study, we found no evidence of peripherally enriched rodent CB1 isoforms; however, some mCB1R isoforms are absent in peripheral tissues. We show that the mouse Cnr1 gene contains six exons that are transcribed from a single promoter. We found that mCB1A is a spliced variant of extended exon 1 and protein-coding exon 6; mCB1B is a novel spliced variant containing unspliced exon 1, intron 1, and exon 2, which is then spliced to exon 6; and mCB1C is a spliced variant including all 6 exons.
Using RNAscope in situ hybridization, we show that the isoforms mCB1A and mCB1B are expressed at a cellular level and colocalized in GABAergic neurons in the hippocampus and cortex. RT-qPCR reveals that mCB1A and mCB1B are enriched in the brain, while mCB1B is not expressed in the pancreas or the liver. Rat rCB1R isoforms are differentially expressed in primary cultured neurons, astrocytes, and microglia.
We also investigated modulation of Cnr1 expression by insulin in vivo and carried out in silico modeling of CB1R with JD5037, a peripherally restricted CB1R inverse agonist, using the published crystal structure of hCB1R.
The results provide models for future CB1R peripheral targeting.”
“Depression associated with diabetes has been described as a highly debilitating comorbidity. Due to its complex and multifactorial mechanisms, the treatment of depression associated with diabetes represents a clinical challenge.
Cannabidiol (CBD), the non-psychotomimetic compound derived from 
“The pharmacological importance of cannabidiol (CBD) has been in study for several years.
CBD is the major nonpsychoactive constituent of plant