This Is MS Multiple Sclerosis Community: Knowledge & Support

I don't know if this abstract has been posted here before, but it looks interesting and may provide a potential role for insulin in reducing inflammation. By the way, the abstract can be found on page 9 of the linked document.

Macronutrient intake induces oxidative and inflammatory stress while insulin causes suppression of reactive oxygen species generation and inflamamtion
Paresh Dandona, Kaleida Health, Buffalo, NY, USA

Following our original observation that the intake of 75g of glucose in normal subjects induces an increase in ROS generation by mononuclear cells (MNC), we have shown that glucose, equi- caloric amounts of fat (eaten as cream) and a mixed fast food meal (900 calories) induce not only an increase in ROS generation by MNC but also cause an increase in p47 phox expression. In addi- tion, there is an increase in intranuclear NF B binding, a fall in IkB expression and an increase in IKK and IKK expression. There is a concomitant increase in TNFa mRNA in the MNC. Two other pro-inflammatory transcription factors, activator protein-1 (AP-1) and early growth response-1 (Egr-1), were also induced by glucose intake. There was an increase in MMP-2, MMP-9, tissue factor (TF) and PAI-1. Thus, there occurs a comprehensive oxida- tive and inflammatory stress response following macronutrient in- take. Consistent with this concept, the state of obesity, associated with increased macronutrient intake, is characterized by an in- crease in oxidative stress and chronic low grade inflammation. As would be expected, caloric restriction in the obese results in a marked reduction in ROS generation by MNC and other indices of oxidative stress, like lipid peroxidation and protein carbonylation. A 48 hour fast in normal subjects leads to a reduction in ROS gen- eration by 50% and a parallel reduction in p47phox. In contrast to macronutrient intake, a low dose insulin infusion (2 units per hour), results in a significant reduction in ROS generation by MNC, p47phox expression, intranuclear NF B binding with an in- crease in IkB expression. In addition, there is a suppression of AP-1 and Egr-1, MMP-2, MMP-9, PAI-1 and tissue factor (TF). This allows us to conclude that there exists a novel relationship between macronutrient intake and insulin, the hormone secreted in response to macronutrient intake.

NHE

NHE, I appreciate the info concerning insulin. For some reason I could not connect to the document, but read and re-read the abstract. I had several problems with it and the conclusion--perhaps a function of my nonscientific mind.

The lingo was beyond me: what is ROS? p47 phox expression. IKK, etc.? But I tried to understand!

I understand the elements induced by glucose, I am sure it promotes inflammation. I accept the association of obesity and inflammation. I don't see how the author can ascribe a reduction in inflammation markers to an insulin infusion. My questions are: Were all other variables controlled? Was diet accounted for? How many subjects were examined? Perhaps these were covered in the entire document.

The last sentence, "This allows us to conclude...", doesn't seem justified by the evidence to me. But, remember, I'm no scientist!

Please keep looking for me; you have sources that are way beyond me.

ros is in the title, reactive oxygen species

p47 phox:
Neutrophils require a set of enzymes to produce reactive oxygen species to destroy bacteria after their phagocytosis. Together these enzymes are termed "phagocyte NADPH oxidase" (phox). Defects in one of these enzymes can all cause CGD of varying severity, dependent on the defect. There are over 410 known defects in the enzyme complex[1].(wikipedia)

ikk is i-kappa-kinase http://en.wikipedia.org/wiki/Kinase

Thank you, both.

General background information on NF-kB and IKK can be found at http://en.wikipedia.org/wiki/NF-kB.

NHE

I am a T1 Diabetic and I have insulin running thru my body 24/7 (pump). I have real good control and use real little insulin. Wow, this is real interesting.

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Mars