Glucose-regulated insulin production in the liver improves glycemic control in type 1 diabetic mice.

ABSTRACT: OBJECTIVE:Type 1 diabetes results from autoimmune destruction of beta-cells in the pancreas. Our objective is to reconstitute a glucose-responsive system in the liver to regulate hepatic insulin production for improving glycemic control in type 1 diabetes. METHODS:We have cloned the glucose-responsive element (GRE) from the promoter of acetyl-CoA carboxylase (ACC), an enzyme that catalyzes the rate-limiting step in fatty acid synthesis in the liver in response to glucose. To increase the amplitude of glucose induction, we quadruplicated the GRE DNA by gene duplication. The resulting GRE multimer (4×GRE) was tested for its ability to drive rat proinsulin cDNA expression in hepatocytes and insulin-deficient diabetic mice. RESULTS:We showed that this GRE multimer-directed glucose-responsive s

SUBMITTER: Zhang T 

PROVIDER: S-EPMC4314533 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature