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Endocannabinoids trigger inflammation that leads to diabetes
National Institutes of Health ^ | August 19, 2013 | NA

Posted on 08/21/2013 5:39:52 PM PDT by neverdem

NIH scientists identify possible treatment target for type 2 diabetes

Researchers at the National Institutes of Health 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.

A report of the finding appears online in Nature Medicine.

“This study is a significant milestone in an ongoing exploration of the endocannabinoid system’s role in the metabolic complications of obesity,” says Kenneth R. Warren, Ph.D., acting director of NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA), which led the study.

Endocannabinoids are natural messengers in the body that help regulate many biological functions. They are chemically similar to the active compound in marijuana. Recent studies have tied endocannabinoids to the metabolic problems that lead to diabetes.  Researchers also have recognized that inflammation appears to play an important role in the pathology of diabetes. 

“The identities of the molecular and cellular actors in the inflammatory processes that underlie type 2 diabetes have remained elusive,” explains senior author and NIAAA scientific director George Kunos, M.D., Ph.D.  “Our study connects endocannabinoids to an inflammatory cascade leading to the loss of beta cells in the pancreas, which is a hallmark of type 2 diabetes.”

Working with a strain of genetically obese rats that serve as a model for human type 2 diabetes, Dr. Kunos and his colleagues used a combination of pharmacological and genetic tools to show that endocannabinoids trigger receptors on macrophages in the pancreas.  Macrophages are immune system cells, present in all tissues that rid the body of cellular debris and pathogens.

“Like various other peripheral tissues, such as the liver, skeletal muscles, pancreas, and fatty tissue, macrophages have receptors for endocannabinoids,” explains Dr. Kunos.

The researchers demonstrated that endocannabinoid activation of macrophages in the pancreas leads to activation of a protein complex within macrophages called the Nlrp3 inflammasome.  The inflammasome, in turn, releases molecules that cause the death of pancreatic beta cells and the progression of type 2 diabetes in the rats.

“When we treated the rats with compounds that deplete macrophages or block all peripheral cannabinoid receptors, inflammasome activation and type 2 diabetes progression was slowed,” noted Dr. Kunos.

In test tube experiments, the researchers showed that macrophages from humans and mice produced the same inflammasome response when they were incubated with endocannabinoids.  However, mouse macrophages that were genetically altered to lack cannabinoid receptors or inflammasomes generated no such response.

Most notably, the researchers showed that by selectively blocking the expression of cannabinoid receptors on macrophages, they could protect and restore beta cell function in the genetically obese rats, which delayed the development and reduced the severity of their diabetes.

The authors conclude that the findings point to a key role in type 2 diabetes for endocannabinoid-induced inflammasome activation in macrophages, and identify cannabinoid receptors on macrophages as a new therapeutic target.

“To understand type 2 diabetes, a public health threat that affects young and old alike, we need to consider all the factors at play,” said Monica Skarulis, M.D., staff clinician at National Institute of Diabetes and Digestive and Kidney Diseases and co-author. “We hope that what we’ve learned from this research will help us develop new strategies to prevent and treat the condition.”

In addition to Dr. Kunos’ team of NIAAA scientists and Dr. Skarulis, co-authors on the study included researchers from the University of Colorado Medical Campus, Aurora, and the University of Massachusetts Medical School, Worcester.

The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at http://www.niaaa.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH...Turning Discovery Into Health®

Reference

Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes. Jourdan, T, et al. Nature Medicine. 2013 August 18. [Epub ahead of print]


TOPICS: Health/Medicine
KEYWORDS: chemicals; diabetes; foodsupply; health; nlrp3inflammasome; obesity; type2diabetes

1 posted on 08/21/2013 5:39:52 PM PDT by neverdem
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To: neverdem

The munchies cause the dia-beatus. Better eat more Quaker oatmeal to offset it.


2 posted on 08/21/2013 5:46:47 PM PDT by goodwithagun (My gun has killed fewer people than Ted Kennedy's car.)
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To: neverdem

3 posted on 08/21/2013 5:47:13 PM PDT by WVKayaker ("Our nation endures and our government... has not perished from the earth."-Sarah Palin 7/1/13)
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To: neverdem

There had been a cannabinoid antagonist under development several years back as a weight loss drug. IIRC studies showed it averaged causing 15 lbs weight loss, and significantly reduced rates of cigarette and alcohol consumption. But it had side effects - mainly psychiatric I think - sufficient that the FDA didn’t approve it. I don’t recall reading anything about diabetes rates and it. I wonder if there is any valid scientific data on the incidence of type I diabetes in pot smokers?


4 posted on 08/21/2013 5:50:03 PM PDT by JohnBovenmyer (Obama been Liberal. Hope Change!)
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To: JohnBovenmyer

cannabidiol is anti-inflammatory

Psychopharmacology (Berl). 2012 Feb;219(4):1133-40. doi: 10.1007/s00213-011-2449-3. Epub 2011 Aug 26.
Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.
Fagherazzi EV, Garcia VA, Maurmann N, Bervanger T, Halmenschlager LH, Busato SB, Hallak JE, Zuardi AW, Crippa JA, Schröder N.
Source

Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, Rio Grande do Sul, Brazil.
Abstract
RATIONALE:

Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases.
OBJECTIVES:

We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats.
METHODS:

Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training.
RESULTS:

A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats.
CONCLUSIONS:

The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

PMID:
21870037


5 posted on 08/21/2013 6:02:56 PM PDT by kruss3
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To: JohnBovenmyer
You are correct. The generic was rimonabant. However, it is a central antagonist, and the article emphasizes peripheral endocannabinoid activity, so they may be unrelated.
6 posted on 08/21/2013 6:38:13 PM PDT by Pharmboy (Democrats lie because they must.)
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To: austinmark; FreedomCalls; IslandJeff; JRochelle; MarMema; Txsleuth; Newtoidaho; texas booster; ...
Insulin Pumps Better Than Injections for Kids With Type 1 Diabetes: Study

One Step Forward for DIY Health Care (Walter Russell Mead)

"The nucleotide-binding domain leucine-rich repeat (NLR)-containing family of pattern recognition receptors includes several proteins that drive inflammation in response to a wide variety of molecular patterns," appears to be involved with the inflammatory response and the innate immune system, much like magrophages. This NIH report about endocannabinoid receptors might explain how type 2 diabetics become insulin dependent.

FReepmail me if you want on or off the diabetes ping list.

7 posted on 08/22/2013 10:27:14 AM PDT by neverdem (Register pressure cookers! /s)
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To: JohnBovenmyer

Every drug has side effects, and sometimes they don’t show up for years. The body always reacts to what is done to it and tries to maintain the status quo. There may never be a satisfactory drug to treat type 2 diabetes. Just lowering the numbers does not address the underlying disease. It remains to be seen if the hypoglycemic drugs currently in use actually prevent the long term complications associated with the disease, or if they cured the cough but left the pneumonia. :-(


8 posted on 08/22/2013 5:59:21 PM PDT by Pining_4_TX (All those who were appointed to eternal life believed. Acts 13:48)
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To: JohnBovenmyer

>> “I wonder if there is any valid scientific data on the incidence of type I diabetes in pot smokers?” <<

.
Probably not, by observation anyway.

Heavy pot smokers tend to eat far more than the average person, yet are usually unable to put on weight. That would tend to indicate that they have no excess glucose in their bodies, since high glucose levels are the most comon cause of weight gain.


9 posted on 08/22/2013 8:23:51 PM PDT by editor-surveyor (Freepers: Not as smart as I'd hoped they'd be)
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To: goodwithagun

I love oatmeal with cinnamon sprinkled on top and eat a lot of it.


10 posted on 08/23/2013 10:25:34 AM PDT by tob2
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