Hepatic expression of the human insulin gene reduces glucose levels in vivo in diabetic mice model

Abstract

The objective of these studies was to evaluate human insulin gene expression following intraliver plasmid injection in diabetic mice as a potential approach to gene therapy for insulin-dependent diabetes mellitus. The fragment containing human proinsulin gene lacking its own promoter, was cloned into plasmids containing promoter and enhancer of cytomegalovirus or human hepatitis B virus. The resulting gene constructs were first tested in vitro using 3T3 fibroblast cell line and subsequently in vivo applying streptozotocin-induced diabetic mice. We found significant reduction in glucose levels in both experimental systems, giving evidence that prolonged constitutive systemic secretion of bioactive human (pro)insulin has been attained in non-neuroendocrine cell line in vitro and in mice following intra-liver plasmid injection. Our data demonstrate the reduction of glucose levels in vitro in 3T3 fibroblast cells and in vivo in diabetic mice after treatment with plasmids expressing proinsulin, giving evidence that those constructs may have certain usage also in human gene therapy of diabetes mellitus type 1.