Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia

Therapy for type 1 diabetes consists of tight blood glucose, (BG) control t o minimize complications Current treatment relies on multiple insulin injec tions or an insulin pump placement, beta -cell or whole pancreas transplant ation. All approaches have significant limitations and have led to the real ization that novel treatment strategies are needed. Pancreatic acinar cells have features that make them a good target for insulin gene transfer. They are not subject to autoimmune attack, a problem with pancreas or islets tr ansplantation, they are avidly transduced by recombinant adenoviral vectors , and capable of exporting a variety of peptides into the portal circulatio n. Recombinant adenoviral vectors were engineered to express either wild-ty pe or furin-modified human insulin cDNA (AdCMVhInsM). Immunodeficient mice were made diabetic with streptozotocin and injected intrapancreatically wit h the vectors. BG and blood insulin levels have normalized after administra tion of AdCMVhInsM. Immunohistochemistry and electron microscopy showed the presence of insulin in acinar cells throughout the pancreas and localizati on of insulin molecules to acinar cell vesicles. The data clearly establish a relationship between intrapancreatic vector administration, decreased BG and elevated blood insulin levels. The findings support the use of pancrea tic acinar cells to express and secrete insulin into the blood stream.