[Diabetes-talk] FW: possible new way to treat type 1 diabetes

[Mike Freeman]

From: acb-diabetics-bounces at acb.org [mailto:acb-diabetics-bounces at acb.org]
On Behalf Of Patricia LaFrance-Wolf
Sent: Saturday, April 02, 2011 3:35 PM
To: 'Discussion list for diabetics and/or ACB issues'
Subject: [acb-diabetics] possible new way to treat type 1 diabetes

 


 

 


Researchers Find Potential New Non-Insulin Treatment for Type 1 Diabetes


1-Apr-2011

March 2011 - Researchers at UT Southwestern Medical Center have discovered a
hormone pathway that potentially could lead to new ways of treating type 1
diabetes independent of insulin, long thought to be the sole regulator of
carbohydrates in the liver. Results of this new study will be published
March 25 in Science.

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., involves taking
insulin multiple times a day to metabolize blood sugar.

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.

The study's lead author is Serkan Kir, a UT Southwestern graduate student in
pharmacology. Also involved in the study were researchers from Yale
University School of Medicine; Case Western Reserve University; Van Andel
Research Institute; and the Howard Hughes Medical Institute.

The work was supported by the National Institutes of Health, HHMI, the
Robert Welch Foundation and the Yale and Case Western Reserve University
Mouse Metabolic Phenotyping Centers.

Source: UT Southwestern Medical Center 

 

-------------- next part --------------
An embedded and charset-unspecified text was scrubbed...
Name: Untitled attachment 00155.txt
URL: <http://nfbnet.org/pipermail/diabetes-talk_nfbnet.org/attachments/20110402/37c8327d/attachment.txt>