(Journal Article): Insulin gene transfer enhances the function of human islet grafts.
 
Deng S, Vatamaniuk M, Lian MM, Doliba N, Wang J, Bell E, Wolf B, Raper S, Matschinsky FM, Markmann JF (The Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA)
 
IN: Diabetologia 2003; 46(3):386-393
Impact Factor(s) of Diabetologia: 5.583 (2004), 5.689 (2003), 5.136 (2002), 6.299 (2001)

Fulltext:    HTML  PDF

ABSTRACT: AIMS/HYPOTHESIS: Recent success in islet transplantation renews the hope for the complete cure of patients afflicted with Type 1 diabetes. However, in the Edmonton series, two to four pancreas donors were required to obtain a sufficient islet mass to reverse the diabetes of each patient. In view of the donor shortage, this represents a major obstacle preventing greater application of islet transplantation to diabetic patients. We hypothesised that increasing the expression of the insulin gene in transplanted islets would augment their capacity for insulin production, thereby allowing reversal of diabetes with a reduced islet mass. METHODS: We used a replication defective adenovirus to deliver the human proinsulin gene (Ad-Ins) to isolated human islets. The function of Ad-Ins-transduced human islets was compared to islets transduced with a control vector (Ad-lacz). RESULTS: Ad-Ins-transduced islets produced two to three times more insulin than normal islets or those infected with Ad-lacz, as assessed by in vitro perifusion tests of glucose stimulated insulin release. When transplanted, Ad-Ins-transduced islets normalised the blood glucose of diabetic immunodeficient NOD-Scid mice, and less than half as many Ad-Ins islets were required for reversal of diabetes than when normal islets were transplanted. CONCLUSION/INTERPRETATION: Our results suggest a simple and effective approach that could enhance the efficiency of islet transplantation for treatment of diabetes in humans.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Emamaullee JA, Rajotte RV, Liston P, Korneluk RG, Lakey JR, Shapiro AM, Elliott JF. XIAP overexpression in human islets prevents early posttransplant apoptosis and reduces the islet mass needed to treat diabetes. Diabetes 2005. 54: 2541-2548.
  » Diabetes OD » Regeneration of Islets » Transplantation » Islet Cells » Inhibition of Apoptosis » Journal Article