Stable insulin-secreting ducts formed by reprogramming of cells in the liver using a three-gene cocktail and a PPAR agonist.

ABSTRACT: With the long-term aim of developing a new type of therapy for diabetes, we have investigated the reprogramming of liver cells in normal mice toward a pancreatic phenotype using the gene combination Pdx1, Ngn3, MafA. CD1 mice were rendered diabetic with streptozotocin and given a single dose of Ad-PNM, an adenoviral vector containing all three genes. Ad-PNM induced hepatocytes of the liver to produce insulin, and the blood glucose became normalized. But over several weeks, the insulin-positive cells were lost and the blood glucose rose back to diabetic levels. Simultaneous administration of a peroxisome-proliferator-activated receptor agonist, WY14643, caused remission of diabetes at a lower dose of Ad-PNM and also caused the appearance of a population of insulin-secreting ductal structure

SUBMITTER: Banga A 

PROVIDER: S-EPMC3880604 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature