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Posted by Susan on November 13, 2007, 12:54 pm
x-no-archive: yes
Well, I'm not a mouse, but my fatty liver was caused by the insulin
sensitizer metformin, and my liver enzymes returned to the lowest end of
normal when I went off of it. My fasting insulin, even as type 2 DM,
is 5.8 on a very low carb diet.
Susan
jay wrote:
> www.sciencedaily.com/releases/2007/11/071106133106.htm
>
> Type 2 Diabetes: Inflammation, Not Obesity, Cause Of Insulin
> Resistance
>
> ScienceDaily (Nov. 7, 2007) - Researchers at the University of
> California, San Diego (UCSD) School of Medicine have discovered that
> inflammation provoked by immune cells called macrophages leads to
> insulin resistance and Type 2 diabetes. Their discovery may pave the
> way to novel drug development to fight the epidemic of Type 2 diabetes
> associated with obesity, the most prevalent metabolic disease
> worldwide.
>
> In recent years, it has been theorized that chronic, low-grade tissue
> inflammation related to obesity contributes to insulin resistance, the
> major cause of Type 2 diabetes. In research done in mouse models, the
> UCSD scientists proved that, by disabling the macrophage inflammatory
> pathway, insulin resistance and the resultant Type 2 diabetes can be
> prevented.
>
> The findings of the research team, led by principle investigators
> Michael Karin, Ph.D., Professor of Pharmacology in UCSD's Laboratory
> of Gene Regulation and Signal Transduction, and Jerrold Olefsky,
> Distinguished Professor of Medicine and Associate Dean for Scientific
> Affairs, will be published as the feature article of the November 7
> issue of Cell Metabolism.
>
> "Our research shows that insulin resistance can be disassociated from
> the increase in body fat associated with obesity," said Olefsky.
>
> Macrophages, found in white blood cells in the bone marrow, are key
> players in the immune response. When these immune cells get into
> tissues, such as adipose (fat) or liver tissue, they release
> cytokines, which are chemical messenger molecules used by immune and
> nerve cells to communicate. These cytokines cause the neighboring
> liver, muscle or fat cells to become insulin resistant, which in turn
> can lead to Type 2 diabetes.
>
> The UCSD research team showed that the macrophage is the cause of this
> cascade of events by knocking out a key component of the inflammatory
> pathway in the macrophage, JNK1, in a mouse model. This was done
> through a procedure called adoptive bone marrow transfer, which
> resulted in the knockout of JNK1 in cells derived from the bone
> marrow, including macrophages.
>
> With this procedure, bone marrow was transplanted from a global JNK1
> knockout mouse (lacking JNK1 in all cell types) into a normal mouse
> that had been irradiated to kill off its endogenous bone marrow. This
> resulted in a chimeric mouse in which all tissues were normal except
> the bone marrow, which is where macrophages originate. As a control,
> the scientists used normal, wild-type mice as well as mice lacking
> JNK1 in all cell types. These control mice were also subjected to
> irradiation and bone marrow transfer.
>
> The mice were all fed a high-fat diet. In regular, wild-type mice,
> this diet would normally result in obesity, leading to inflammation,
> insulin resistance and mild Type 2 diabetes. The chimeric mice,
> lacking JNK1 in bone marrow-derived cells, did become obese; however,
> they showed a striking absence of insulin resistance -- a pre-
> condition that can lead to development of Type 2 diabetes.
>
> "If we can block or disarm this macrophage inflammatory pathway in
> humans, we could interrupt the cascade that leads to insulin
> resistance and diabetes," said Olefsky. "A small molecule compound to
> block JNK1 could prove a potent insulin-sensitizing, anti-diabetic
> agent."
>
> The research also proved that obesity without inflammation does not
> result in insulin resistance. Olefsky explained that when an animal or
> a human being becomes obese, they develop steatosis, or increased fat
> in the liver. The steatosis leads to liver inflammation and hepatic
> insulin resistance.
>
> The chimeric mice did develop fatty livers, but not inflammation.
> "Their livers remained normal in terms of insulin sensitivity," said
> Olefsky, adding that this shows that insulin resistance can also be
> disassociated from fatty liver.
>
> "We aren't suggesting that obesity is healthy, but indications are
> promising that, by blocking the macrophage pathway, scientists may
> find a way to prevent the Type 2 diabetes now linked to obesity and
> fatty livers," Olefsky said.
>
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