Posted on 01/31/2005 4:29:19 PM PST by QQQQQ
The researchers, from Joslin Diabetes Center in Boston, discovered a genetic ''master switch" in the liver that is turned on when people become obese. Obesity has long been linked to diabetes, but the reason, until now, has been unknown. Joslin researchers found that once on, this switch produces low-level inflammation, which disrupts the body's ability to process insulin, causing type 2 diabetes.
Reasoning that aspirin-like drugs are used to quell inflammation, they successfully used the drugs, called salicylates, to eliminate the symptoms of type 2 diabetes in mice. Human tests are already underway in Boston, though no results have been published.
''These drugs, among the safest drugs known, can do a surprisingly good job of toning down this inflammation," said Joslin researcher Dr. Steven E. Shoelson, lead author of the paper.
Shoelson's team began the experiment seeking the biological connections between weight gain and diabetes. Livers of obese people accumulate fat faster than any other organ, and that many overweight diabetic patients had high levels of proteins -- particularly one called NF-kB -- in their livers that normally trigger inflammation.
They zeroed in on it and were stunned to discover its role in diabetes. The scientists were able to trigger inflammation and the symptoms of diabetes in lean, previously healthy mice by using genetic techniques to turn on the gene that makes NF-kB.
Shoelson's team decided to use salicylates, already used as anti-inflammatories, to try to stop low-level inflammation and diabetes symptoms triggered by NF-kB -- and was successful. As long as the mice got adequate doses, their diabetes was held in check. Aspirin is the best known of this family of drugs. But Shoelson found that it would take more than 20 aspirins daily to suppress NF-kB in human diabetics, which would cause severe gastrointestinal bleeding.
(Excerpt) Read more at boston.com ...
ping
So9
Chlamydia pneumoniae Activates Epithelial Cell Proliferation via NF-¦ÊB and the Glucocorticoid Receptor
Mikael M. Cornelsen Gencay,1,2* Michael Tamm,1 Allan Glanville,2 Andr¨¦ P. Perruchoud,1 and Michael Roth1,3
Department of Research, Pulmonary Cell Research, University Hospital Basel, Switzerland1 Heart and Lung Transplant Unit, St. Vincent's Hospital2 The Woolcock Institute for Medical Research, University of Sydney, Sydney, Australia3
Received 2003 January 24; Revised 2003 April 2; Accepted 2003 June 17.
Abstract
Chlamydia pneumoniae is an obligate intracellular eubacterium and a common cause of acute and chronic respiratory tract infections. This study was designed to show the effect of C. pneumoniae on transcription factor activation in epithelial cells. The activation of transcription factors by C. pneumoniae was determined in human epithelial cell lines (HL and Calu3) by electrophoretic DNA mobility shift assay, Western blotting, and luciferase reporter gene assay. The activation of transcription factors was further confirmed by immunostaining of C. pneumoniae-infected HL cells and mock-infected controls. The effect of transcription factors on C. pneumoniae-induced host cell proliferation was assessed by [3H]thymidine incorporation and direct cell counting in the presence and absence of antisense oligonucleotides targeting transcription factors or the glucocorticoid receptor (GR) antagonist RU486. The activation of the GR, CCAAT-enhancer binding protein (C/EBP), and NF-¦ÊB was induced within 1 to 6 h by C. pneumoniae. While the interleukin-6 promoter was not activated by C. pneumoniae, the GR-driven p21(Waf1/Cip1) promoter was increased 2.5- to 3-fold over controls 24 h after infection. C. pneumoniae dose-dependently increased the DNA synthesis of the host cells 2.5- to 2.9-fold, which was partly inhibited either by RU486 or by NF-¦ÊB antisense oligonucleotides. Furthermore, we provide evidence that heat-inactivated C. pneumoniae does not cause a significant increase in cell proliferation. Our results demonstrate that C. pneumoniae activates C/EBP-¦Â, NF-¦ÊB, and the GR in infected cells. However, only NF-¦ÊB and the GR were involved in C. pneumoniae-induced proliferation of epithelial cells.
But according to the abstract, the chlamydia did induce NF-kB production.
Soon chlamydia will be recognized for its role in heart disease, diabetes, rheumatoid arthritis, and a host of other immunopathies.
Very interesting. Thanks for the info.
I agree, and can believe, that we may ultimately find out, that inflammation caused by some viruses and bacteria -- chlamydia could just be one of several -- is the root cause of malfunctioning of organs in the body, such as the liver, which ultimately results in obesity, diabetes, hardening of the arteries, heart disease ( they already recognize that inflammation plays a role, that's why they started to measure CRP), arthritis, MS, and even cancer.
How about a cure for TYPE 1 diabetes.....you know, the insulin dependent kind with needles and finger pricks.....?
Obesity and diabetes. Hmmm. What about all those people who have never ever been obese and still have diabetes and heart problems, etc. What triggers these diseases in people who are of normal weight or who are thin?
book mark
Thanks, Q.
"The scientists were able to trigger inflammation and the symptoms of diabetes in lean, previously healthy mice by using genetic techniques to turn on the gene that makes NF-kB. "
I think it may turn out, that obesity and diabetes are a result of this genetic trigger going haywire, instead of the cause.
I'm type II and I still finger prick.
The Chlamydia connection to coronary artery disease/inflamation has been recognized for many years. I'm not sure that one can make the leap to Chlamydia activation of NF-kB as a cause of Diabetes. There may be other mechanisms for NF-kB activation. Nevertheless, an interesting set of observations.
I was going to write a technical appraisal to bore you with but heck . . . Go Joslin Guys! We are on the verge of defeating this sumbitch!!
To a certain extent, it's hereditary.
My father's side of the family has an extensive history of late onset diabetes.
His condition would be much more manageable, if there weren't other complicating health issues.
Plaque builds up on your heart/lungs after forty or so years of chronic smoking, so that is much more of a lethal factor, to be perfectly honest.
My point is, a lot of the disorders that may be inherited from one generation to the next are compounded by poor lifestyle choices, as in my immediate family.
Diabetes, both types, seems to run in the family. So far, doing well with lifestyle changes and using alternative treatments such as dandelion tea, Jerusalem artichokes and guar gum. It's much harder to deal with any illness when it's inherited.
My daughter's diabetes came out of nowhere last summer. No family history, no nothing. She's only 8 but started doing her own shots about a week out of the hospital. I would gladly be the diabetic in her place but alas, it doesn't work that way. We're hoping the adult stem cell research brings us some good news in years to come.
The people in the state of California, who were duped into approving this fiscal and moral boondoggle called stem cell research, will be sorely disappointed if they expect any medical miracles to result from the passage of that initiative.
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