The surprise of course is thatthere is an additional pathway besides insulin though one not so obviouslyuseful. It suggests that a balanceexists that needs to be discovered and understood that might explain the irregularitiesin insulin therapies.
As posted before, the great hopefor diabetics will be and is stem cell therapy. That will surely outrun hormonal pathways to the finish line.
In the meantime we will learnmuch about the issues and improve upon present practice.
Researchers find potential new non-insulin treatment for type 1diabetes
Researchers at UT Southwestern Medical Center
Another hormone, fibroblast growth factor 19 (FGF19), has insulin-likecharacteristics beyond its role in bile acid synthesis. Unlike insulin,however, FGF19 does not cause excess glucose to turn to fat, suggesting thatits activation could lead to new treatments for diabetes or obesity.
"The fundamental discovery is that there is a pathway that existsthat is required for the body, after a meal, to store glucose in the liver anddrive 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 diabetestreatments outside of insulin therapy. Thestandard treatment for type 1 diabetes, whichaffects about 1 million people in the U.S.
Dr. Mangelsdorf and Dr. Steven Kliewer, professor of molecular biologyand pharmacology atUT Southwestern, are co-senior authors of the study. Dr. Kliewer has beenstudying the hormone FGF19 since he discovered its involvement in metabolismabout eight years ago.
Fibroblast growth factors control nutrient metabolism and are releasedupon bile acid uptake into the small intestine. Bileacids, produced by the liver, break down fats in the body.
Researchers studied mice lacking FGF15 – the rodent FGF19 hormoneequivalent. These mice, after eating, could not properly maintain bloodconcentrations of glucose and normal amounts of liver glycogen. Glycogen is aform of glucose storage found mainly in liver and muscle tissue. The mice werethen injected with FGF19 to evaluate its effects on metabolism in the liver.
FGF19 restored glycogen levels in the mice lacking FGF15. Whenadministered to diabetic mice lacking insulin, FGF19 also corrected the loss ofglycogen.
"FGF19 does not make fat, and that's one of the effects thatseparates it from insulin. Insulin also does not really have a dramatic effecton bile acid synthesis. So, the two pathways are different even though theyboth function in glycogen and protein synthesis,"said Dr. Mangelsdorf, a Howard Hughes Medical Institute investigator at themedical center.
Manipulating FGF19 as an alternative to insulin therapy remains adaunting challenge, however, given some unwelcome side effects. In somestudies, he said, activating the hormone in rodents caused the liver to growand develop cancer.
One promising diabetes treatmentroute could involve the nuclear bile acid receptor FXR, which Dr. Mangelsdorfsaid induces expression of FGF19. Modulators of FXR (farnesoid X receptor) havebeen shown to lower triglycerides and improve cholesterol profiles inpreclinical models.
Post a Comment