The surprise of course is that
there is an additional pathway besides insulin though one not so obviously
useful. It suggests that a balance
exists that needs to be discovered and understood that might explain the irregularities
in insulin therapies.
As posted before, the great hope
for diabetics will be and is stem cell therapy.
That will surely outrun hormonal pathways to the finish line.
In the meantime we will learn
much about the issues and improve upon present practice.
Researchers find potential new non-insulin treatment for type 1
diabetes
Researchers at UT Southwestern
Medical Center
Another hormone, fibroblast growth factor 19 (FGF19), has insulin-like
characteristics beyond its role in bile acid synthesis. Unlike insulin,
however, FGF19 does not cause excess glucose to turn to fat, suggesting that
its activation could lead to new treatments for diabetes or obesity.
"The fundamental discovery is that there is a pathway that exists
that is required for the body, after a meal, to store glucose in the liver and
drive protein synthesis. That pathway is independent of insulin," said Dr.
David Mangelsdorf, chairman of pharmacology at UT Southwestern.
Naturally elevating this pathway, therefore, could lead to new diabetes
treatments outside of insulin therapy. The
standard treatment for type 1 diabetes, which
affects about 1 million people in the U.S.
Dr. Mangelsdorf and Dr. Steven Kliewer, professor of molecular biology
and pharmacology at
UT Southwestern, are co-senior authors of the study. Dr. Kliewer has been
studying the hormone FGF19 since he discovered its involvement in metabolism
about eight years ago.
Fibroblast growth factors control nutrient metabolism and are released
upon bile acid uptake into the small intestine. Bile
acids, produced by the liver, break down fats in the body.
Researchers studied mice lacking FGF15 – the rodent FGF19 hormone
equivalent. These mice, after eating, could not properly maintain blood
concentrations of glucose and normal amounts of liver glycogen. Glycogen is a
form of glucose storage found mainly in liver and muscle tissue. The mice were
then injected with FGF19 to evaluate its effects on metabolism in the liver.
FGF19 restored glycogen levels in the mice lacking FGF15. When
administered to diabetic mice lacking insulin, FGF19 also corrected the loss of
glycogen.
"FGF19 does not make fat, and that's one of the effects that
separates it from insulin. Insulin also does not really have a dramatic effect
on bile acid synthesis. So, the two pathways are different even though they
both function in glycogen and protein synthesis,"
said Dr. Mangelsdorf, a Howard Hughes Medical Institute investigator at the
medical center.
Manipulating FGF19 as an alternative to insulin therapy remains a
daunting challenge, however, given some unwelcome side effects. In some
studies, he said, activating the hormone in rodents caused the liver to grow
and develop cancer.
One promising diabetes treatment
route could involve the nuclear bile acid receptor FXR, which Dr. Mangelsdorf
said induces expression of FGF19. Modulators of FXR (farnesoid X receptor) have
been shown to lower triglycerides and improve cholesterol profiles in
preclinical models.
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