Science

Islet neogenesis reverses diabetes in mice: primate studies planned

Last Updated: 2006-06-02 18:26:03 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - In diabetic mice, in vivo delivery of the neurogenin 3 (Ngn3) and betacellulin (BtC) genes induces liver cells to reprogram into mature islets containing glycemia-regulated, insulin-producing beta cells that restore normoglycemia and reverse diabetes.

Dr. Lawrence Chan from Baylor College of Medicine in Houston presented the research Friday at the 9th annual meeting of the American Society of Gene Therapy in Baltimore, Maryland.

Ngn3 is "an islet lineage defining transcription factor ... sufficient and necessary for normal islet development," Dr. Chan and colleagues explain in meeting materials. BtC is an islet growth factor.

In diabetic mice, a single injection of Ngn3 and BtC, using a helper-dependent adenoviral vector, restored normoglycemia within one week and this persisted for at least nine weeks, Dr. Chan reported.

Quantitative reverse-transcriptase polymerase chain reaction showed the presence of the islet hormones Ins1, Ins2, and glucagon in the livers of treated mice, and immunostaining revealed clusters of insulin-positive cells next to glucagon-positive cells, as seen in mature islets.

The current studies build on previous research by Dr. Chan's group in which they successfully reversed diabetes in mice by transferring BtC and the islet transcription factor NeuroD.

"With this earlier approach, we cured the diabetes and the animals had islet-like structures in the liver," Dr. Chan noted in an interview with Reuters Health, but the islets were not completely "normal." With Ngn3 and BtC, "the islets are much more normal," Dr. Chan said, "and the response was much better this time because we reversed diabetes within one week -- last time it took three weeks."

Equally important, Dr. Chan said, "In the earlier study, we did not know what cells were transformed into islet cells. We did not know whether they came from bone marrow lodged in the liver or came from some other types of cells. Now we have pretty good evidence that many of them were actually liver cells so we actually changed hepatocytes into islets or beta cells that produce insulin."

All of these observations, he said, set the stage for the next phase of studies in monkeys.