Diabetic Inflammation

After reading the article about diabetes the one underlying theme was that of inflammation.  I know that the macrophages are responsible for inflammation but what i didn't get was what part of the body becomes inflamed.  Is there an typical area where inflammation occurs due to diabetes such as in the pancreatic beta cells, the liver or certain muscles or is just simply where the most adipocytes coalesce?

Inflammation in Obesity is Common Link Between Defects of Fatty Acid Metabolism and Insulin Resistance

In this article, Diabetes Type II induced inflammation is more closely examined for the particular pathway regarding Tumor Necrosis Factor alpha (TNFa), although it is important to remember that the relationship between Type II Diabetes and obesity is multi-faceted and not limited to one specific pathway (which makes it so difficult to understand). The basis of this particular pathway proceeds sort of like this: The excess caloric intake and reduced caloric expenditure of modern lifestyle has lead to an increasing rise in obesity, which is due to the rise in fatty acids in the body and thus an increase in adipocytes in which to store the fat. Unfortunately, adipocytes have proven to not be pure storage centers, but have in fact been shown to have significant endocrine and paracrine interaction with surrounding cells, including macrophages. By increasing the number of adipocytes in the body, an increase of macrophages will be recruited to the area and an increase in TNFa production will occur. This article describes how TNFa has been shown to have a variety of implications, including: inflammation (an important role of macrophages), decreased insulin-stimulated glucose disposal, increased insulin resistance, and an increase in protein phosphatase 2C (PP2C). PP2C inhibits another cytokine called AMP-activated phosphokinase (AMPK), which is responsible for helping to maintain proper metabolic balance. These effects all contribute to a decreased level of skeletal muscle fatty acid oxidation, which simply leads to an increase in fatty acid production and repeats the cycle.

Questions: 1)Why do you think macrophages (responsible for TNFa) would be recruited to the area of adipocytes in fat tissue to begin with? 2) Is this recruitment preventable? 3) How much of a real contribution does TNFa have in inducing the inflammatory response in obesity/type II diabetes?

Inflammation: the link between insulin resistance, obesity and diabetes

I'm really interested in how Tumor Necrosis Factor alpha (TNF) is integrated in insulin resistance (Type II diabetes) and the inflammatory response. This article discusses the link between insulin resistance, obesity, and diabetes with TNF and other inflammatory proteins. Basically, TNF is released by a variety of tissues to include adipose tissue, which is concentrated in the obese. TNF works on the liver by promoting phosphorylation of the serine insulator substrate 1 and inhibits auto-phosphorylation of the tyrosine insulin receptor. This has been known to impair insulin signaling therefore resulting in insulin resistance i.e. type II diabetes. It was also interesting to see that TNF inhibitors have been used to treat insulin resistance but have proven unsuccessful...I wonder why? I think it's really interesting to see the biochemistry behind physiological mechanisms. To understand how a car works, you have to learn how the parts work. Good article. Enjoy:D
Inflammation: the link between insulin resistance, obesity and diabetes.
Dandona P, Aljada A, Bandyopadhyay A.

Pig Brain Aerosols

Workers at a meat packing plant whose job was to blow the brains out of pig heads with compressed air have developed what seems to be an inflammatory brain disease. It is likely in this case that the mechanism is immunological. Our brains are antigenic, but as long as we keep them in our head they do not stimulate the immune system. If brain is given by an immunizing route (injected, inhaled) it may stimulate an immune response, when then crosses into the intact brain and attacks it. A typical reference to the brain incident: here

Do you think the man's popcorn problem is also immunological?

Inflammatory Popcorn!!

http://www.nytimes.com/2007/09/05/us/05popcorn.html

The above article is from the New York Times and might be interesting to all of us (It talks about inflammation and the person was diagnosed at National Jewish Hospital in Denver)!!

This article came out last year but it really does lead to some questions about our environment and inflammation. How much that we take for granted has serious effects on our health?

Dr. Cohen at the University of Colorado was telling me about a similar case, but where people were exposed to pig brains...if he's reading this, we would love to read about it!

"Surgery may cure diabetes in overweight"

In the article titled "Surgery may cure diabetes in overweight" (url: http://www.azcentral.com/news/articles/0123obesity-diabetes0123.html ) it states that a common procedure called stomach-band surgery may be an effective treatment for obese individuals with diabetes. According to the Centers for Disease Control (2003), diabetes and obesity are two prominent issues to be dealt with by the American population. More than 44 million are considered obese in the U.S., and 17 million have diabetes.
In the reported study, fifty-five diabetic and obese patients underwent stomach-band surgery. The majority of the participants experienced a remission in their diabetes (the report stated that most patients achieved normal blood tests, and most even stopped taking their diabetic drugs). As intelligent researchers and scientists, we should be skeptic of new treatments and take many issues into consideration.
For example, (1) do the benefits override the risks of stomach-band surgery? and (2) why could stomach-band surgery be more beneficial than other types of weight loss surgery?

Our Immune System: The Sixth Sense?

I came across an article implying another link between our immune system, behavior, and psychology, and could not resist digging a little further and sharing what I read.
Although it is often understood, accepted, and sometimes overlooked that someone suffering from either chronic illness, an acute life-changing medical event, or a terminal disease would experience feelings of depression or even, at times, to end their own life - what if, instead, the immune-boosting medications they were taking or the immunological processes at work in their system was supplying the fuel for their depression?
According to McElroy, 12-30 percent of patients of various diseases with an inflammatory component, also suffer from depressive disorders (News Bureau, 7/27/04). Glassman and Miller, similarly, found that "45% of malignant melanoma patients treated with high-dose alpha interferon developed major depression" (Biological Psychiatry, August, 2007). The statistics abound with depression and suicide suspiciously following administration of two immune-boosters - alpha interferon and interleukin-2 (New Scientist, 16 June 2001).
Dantzer and Kelley believe that the cytokines, boosted by drugs, such as those listed above, activate the enzyme indoleamine-2,3-dioxygenase, which catabolizes tryptophan, thereby preventing it from being turned into serotonin - a known brain regulatory chemical and focus of much of the anti-depressant industry today (News Bureau, 7/24/04). They also invoked fever and sickness-related behavior in mice whose brains were directly injected with cytokines and then found that if they blocked pathways from brain to body, they could inhibit these same sickness behaviors (News Bureau, 7/27/04).
Maes found that people suffering from depression had higher than expected immune system markers: natural-killers cells, monocytes, and macrophages, as opposed to an expected supressed immune system (New Scientist, 16 June 2001). There was even evidence from Germany of a possible viral link to depression, though results were unable to be replicated (New Scientist, 16 June 2001).
The vote is still out it seems - Glassman and Miller site inconsistencies and obviously a complex relationship between cytokines and depression, with much left to be identified and understood (Biological Psychiatry, August 2007).
What if depression were somehow linked to viral infection? What if we could prevent depression associated with illness or major medical procedures with the simple administration of SSRIs? Is the immune system really our sixth sense, telling our bodies to display symptoms of illness and depression? The questions seem neverending.

References:

"Scientists Build on Case Connecting Inflammatory Disease and Depression." McElroy, Molly; News Bureau, 7/27/2004, University of Illinois at Urbana-Champaign.
"A Mind Under Seige." Brown, Phyllida; New Scientist, 16 June 2001.
"Where there is Depression, there is Inflammation, Sometimes!" Glassman, Alexander H., and Miller, Gregory E.; Biological Psychiatry, Volume 62, Issue 4, 15 August 2007, Pages 280-281.

our venerable leaders...

Here is a quote from presidential candidate Mike Huckabee (1992):

"If the federal government is truly serious about doing something with the AIDS virus, we need to take steps that would isolate the carriers of this plague," Huckabee wrote.
"It is difficult to understand the public policy towards AIDS. It is the first time in the history of civilization in which the carriers of a genuine plague have not been isolated from the general population, and in which this deadly disease for which there is no cure is being treated as a civil rights issue instead of the true health crisis it represents."

Camel Antibodies are Strange

I mentioned in class that camel antibodies are heat-resistant, and someone has developed a camel antibody-based dip-stick test for caffeine in hot drinks (see Nature, 11 May 2006, p.169). Becky Buckley told me afterwards that camel Abs are structurally odd, so I did some reading, and find that a majority of them have no L chains, but are H chain dimers! So the MW is more like 100,000 than 150,000. In human Abs, it's hard to get 2 H chains to dimerize, because their association surfaces (part of the V region framework) are "looking" for L chains. So some clever types have "camelized" human H chains, mutating the amino acids that repel other H chains, and successfully made H chain dimers, some of which are biologically active. Nature and biotechnology, aren't they both lovely?

Pig Brain as Antigen?

I realize this post is too late for further class credit, but its too interesting to not post. Therefore I'll keep it short.

I found this story in the press from Minnesota. See the link:

http://news.postbulletin.com/newsmanager/templates/localnews_story.asp?z=2&a=317960

It appears workers in a meat processing plant may have introduced pig brain as antigen while using pressurized air to clean the word environment. There are MS like symptoms (disease unknown at this time), and all affected employees worked near a machine desposing of brain. This sounds like the example JJ gave in class about the lab tech exploding a glass blender, thereby "inoculating" himself with novel antigen.

Very interesting..Do you guys think the symptoms are immunological? What are the hypothetical mechanism? Or alternatives?