Posted on 09/04/2011 12:56:18 PM PDT by decimon
Study finds inflammation may be part of the solution, not the problem
Increased low-grade inflammation in the body resulting from obesity is widely viewed as contributing to type 2 diabetes. Going against this long-held belief, researchers from Children's Hospital Boston report that two proteins activated by inflammation are actually crucial for maintaining good blood sugar levels – and that boosting the activity of these proteins can normalize blood sugar in severely obese and diabetic mice.
The research, led by Umut Ozcan, MD, in the Division of Endocrinology at Children's, is reported in the October issue of Nature Medicine, published online September 4.
"This finding is completely contrary to the general dogma in the diabetes field that low-grade inflammation in obesity causes insulin resistance and type 2 diabetes," says Ozcan. "For 20 years, this inflammation has been seen as detrimental, whereas it is actually beneficial."
Ozcan's team previously showed that obesity places stress on the endoplasmic reticulum (ER), a structure in the cell where proteins are assembled, folded and dispatched to do jobs for the cell. This so-called "ER stress" impairs the body's response to insulin in maintaining appropriate blood glucose levels, and is a key link between obesity and type 2 diabetes. Last year, Ozcan and colleagues showed that a protein that relieves ER stress, called XBP1s, cannot function in obese mice. Earlier this year, they showed that activating XBP1s artificially in the liver normalized high blood sugar in obese, insulin-resistant type 2 diabetic mice (as well as lean, insulin-deficient type 1 diabetic mice).
The new study shows that a second protein triggered by inflammatory signals, p38 MAPK, chemically alters XBP1s, enhancing its activity -- and that without these alterations, XBP1s cannot function to maintain normal glucose levels. The study further showed that obese mice have reduced p38 MAPK activity, and that re-activating p38 MAPK in the liver reduced their ER stress, increased insulin sensitivity and glucose tolerance, and significantly reduced blood glucose levels.
Together, the findings suggest that either increasing p38 MAPK activity -- despite its being an inflammatory signal -- or increasing XBP-1 activity by other means could represent new therapeutic options for diabetes.
The study also suggests a new model for understanding type 2 diabetes, in which obesity may interfere with the ability of people's cells to respond to inflammatory signals. "It may be that inflammatory pathways are not working optimally and there could be a resistance to cytokines which mediates the inflammation," Ozcan says. "This could be a paradigm shift for the field."
The researchers also raise a possible down side in using p38 MAPK inhibitors to treat inflammatory diseases such as Crohn's disease, psoriasis and asthma. "These therapeutic approaches should … be evaluated within the context of our results, and in light of the possibility that inhibition of XBP1s activity also decreases the ability of the cell to cope with the inflammatory conditions," they write.
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The study (doi:10.1038/nm.2449) was supported by the National Institutes of Health and the Timothy Murphy funds provided to the Division of Endocrinology, Children's Hospital Boston. Jaemin Lee, PhD, and Cheng Sun, PhD, were co-first authors on the paper.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 11 members of the Institute of Medicine and nine members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 396 bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Children's, visit: http://vectorblog.org.
*PING* and call all your friends, too.
This is significant.
Cheers!
Lost 70 pounds, hit the gym and controlled my diet. Within a year, my A1C dropped from 6.4 to 5.3 (and holding).
Started off at 315 pounds and looked/felt like an unhappy camper. I’m now down to 243 and life is more enjoyable. Pant size dropped from 54” to 46” and I’m down to 3x shirts. No longer winded on the steps, I can take LONG walks on the local trails (2-3 hours) and can even start to think about dating......ALL OF THIS WITHOUT FRIGGEN OBAMACARE!!!!
Getting my A1C under control means less meds and few trips to the doctor. It’s like a pay increase in a quasi sort of way.
Doc says there’s a good chance that when I reach my target weight of 180 (and keep up the exercise and diet), I could reach an A1C of 5.0 or less. At that point, I’m on a “conditional reprieve”.
I forgot to ping the list.
For reminding me, you get two pings, grey_whiskers. ;-)
Good. Keep up the good work and enjoy.
The next time I get some obese/diabetic mice from the pet store, I'll know what to do!
Congratulations. Those are very significant achievements.
“Lost 70 pounds, hit the gym and controlled my diet”
I am very PROUD of you! I know that dieting and completely changing your lifestyle is not a box of chocolates (no pun intended). You stay with whatever program you are doing... it is obviously working. Good wishes your way for your success!
Nice work!!!!!! Keep up the AWESOME work!
Bump
ping
Wonderful! Congratulations!
Thanks decimon.
Thanks for all the info, decimon. Being on your list is truly helpful.
Thank you. I hope this stuff is helpful. If not then it's just a waste of space.
“I switched to Sweet-n-Low — now I’ve got artificial diabetes!” — Rodney Dangerfield
Thanks grey_whiskers! (whoops)
Definitely not a waste of space! God bless you.
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