Researchers have identified endocannabinoid receptors as a potential therapeutic target for treating type 2 diabetes, revealing the role of inflammation in pancreatic cell death. The endocannabinoid system regulates various biological processes, indicating its potential in addressing several disorders. Further investigation into the endocannabinoid system could provide new therapeutic options for chronic conditions.

1. ENDOCANNABINOID RECEPTORS -
POSSIBLE TREATMENT TARGET FOR TYPE
2 DIABETES
P. Naina Mohamed
Pharmacologist

2. INTRODUCTION
 On 19th Aug 2013, the researchers at the National
Institutes of Health (NIH) have clarified in rodent
and test tube experiments the role that
inflammation plays in type 2 diabetes, and revealed
a possible molecular target for treating the disease.
 The researchers say some natural messenger
chemicals in the body are involved in an
inflammatory chain that can kill cells in the
pancreas, which produces insulin.
 The research found that the macrophage-
expressed peripheral endoconnabinoid (CB1R)
receptors as a therapeutic target in type 2 diabetes
mellitus (T2DM).

3. POSSIBLE MECHANISM OF PATHOGENESIS
Endocannabinoids
Triggers the endocannabinoid receptors found in
macrophages of Pancreas
Activation of Macrophages
Activation of Nlrp3 inflammasome (Protein complex within
macrophages)
Release of molecules causing death of pancreatic beta
cells
Type 2 DM

4. COMPOUNDS OF FUTURE INTEREST
Compounds depleting macrophages (or)
peripheral cannabinoid receptors blockers
Slowing of activation of inflammasome
Slowing of progression of type 2 DM

5. ENDOCANNABINOID SYSTEM
 The endocannabinoid system is a central regulatory
system.
 It affects a wide range of biological processes and its
overall function is to regulate homeostasis which is best
described as the ability to maintain stable internal
conditions that are necessary for survival.
 Current evidence points to the endocannabinoid system
as being a potential therapeutic target for the following
list of disorders: AIDS/HIV, Alzheimer’s
Disease, Arthritis, Cancer, Chronic
Pain, Epilepsy, Fibromyalgia, Glaucoma, Multiple
Sclerosis, Sleep disorders, Post-traumatic Stress
Disorder, and many more…
 It consists of:
 Endocannabinoids
 Endocannabinoid receptors (CB1 and CB2)

6. ENDOCANNABINOIDS
 Endocannabinoids are a type of natural messengers.
 Anandamide is one of the example of endocannabinoids.
 Endocannabinoids are involved in inflammation, insulin
sensitivity, and fat and energy metabolism.
 Endocannabinoids also play a key role in memory, mood, brain
reward systems, drug addiction, and metabolic processes, such
as lipolysis, glucose metabolism, and energy balance.
 Inhibition of endocannabinoids may reduce the prevalence of
metabolic syndrome.
 Modulation of the endocannabinoid system may be a cure for
more chronic neurologic and immune conditions.
 Many questions are left unanswered about this relatively newly
discovered regulatory system. Further investigation into this
exciting field promises to shed insights into the mechanisms of
health and disease and provide new therapeutic options.
 Endocannabinoids are lipophilic in nature hence they act locally
and are not synthesized until needed.

7. ENDOCANNABINOID RECEPTORS
 Endocannabinoid receptors are found in various parts of the body,
but are most prominent in the brain and immune system.
 Researchers have identified cannabinoid receptors in a variety of
other places as well, including the peripheral nervous system,
cardiovascular system, reproductive system, and gastrointestinal and
urinary tracts.
 CB1 and CB2 are G-protein receptors.
 CB1 receptors are abundant in the brain, specifically the
mesocorticolimbic system, the spinal cord, and the peripheral
neurons.
 CB1 receptors are particularly concentrated on gamma-aminobutyric
acid (GABA) – releasing neurons (inhibitory neurons). Hence,
activation of CB1 leads to retrograde suppression of neurotransmitter
release.
 Inactivation of CB1 receptors decreases plasma insulin and leptin
levels, ultimately leading to more efficient energy metabolism.
 CB2 receptors are located peripherally, with a high density on
immune-modulating cells and activated microglial.
 CB2 receptors are involved in maintaining proper bone mass. CB2

8. CB1 RECEPTOR ANTAGONIST
 Rimonabant (Acomplia or Zimulti) is a selective
CB1 receptor antagonist.
 It binds to centrally acting CB1 receptors.
 Rimonabant is currently being sold in the United
Kingdom, Germany, and a few other countries
around the world under the name Acomplia, as an
anti-obesity drug.
 In the United States, rimonabant was rejected by an
expert panel of the FDA.
 However, evidence exists to support the use of
rimonabant in the treatment of obesity, its
comorbidities, and drug dependence.

9. REFERENCES
 http://www.nih.gov/news/health/aug2013/niaaa-
19.htm
 http://www.nature.com/nm/journal/vaop/ncurrent/full
/nm.3265.html
 http://emedicine.medscape.com/article/1361971-
overview#a30
 http://www.niaaa.nih.gov/news-events/news-
releases/endocannabinoids-diabetes