ENDOCANNABINOID RECEPTORS -
POSSIBLE TREATMENT TARGET FOR TYPE
2 DIABETES
P. Naina Mohamed
Pharmacologist
INTRODUCTION
 On 19th Aug 2013, the researchers at the National
Institutes of Health (NIH) have clarified in rodent
and t...
POSSIBLE MECHANISM OF PATHOGENESIS
Endocannabinoids
Triggers the endocannabinoid receptors found in
macrophages of Pancrea...
COMPOUNDS OF FUTURE INTEREST
Compounds depleting macrophages (or)
peripheral cannabinoid receptors blockers
Slowing of act...
ENDOCANNABINOID SYSTEM
 The endocannabinoid system is a central regulatory
system.
 It affects a wide range of biologica...
ENDOCANNABINOIDS
 Endocannabinoids are a type of natural messengers.
 Anandamide is one of the example of endocannabinoi...
ENDOCANNABINOID RECEPTORS
 Endocannabinoid receptors are found in various parts of the body,
but are most prominent in th...
CB1 RECEPTOR ANTAGONIST
 Rimonabant (Acomplia or Zimulti) is a selective
CB1 receptor antagonist.
 It binds to centrally...
REFERENCES
 http://www.nih.gov/news/health/aug2013/niaaa-
19.htm
 http://www.nature.com/nm/journal/vaop/ncurrent/full
/n...
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Endocannabinoid receptors possible treatment target for type 2 dm

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NIH research found that peripheral Endocannabinoid recptors blockers would be used to treat type 2 DM.

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Endocannabinoid receptors possible treatment target for type 2 dm

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

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