Back to Search
Start Over
Glucose tolerance normalization following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic ZDF rats.
- Source :
-
Transplant immunology [Transpl Immunol] 2006 Nov; Vol. 16 (3-4), pp. 176-84. Date of Electronic Publication: 2006 Sep 07. - Publication Year :
- 2006
-
Abstract
- Pancreas or pancreatic islet transplantation in humans is limited by organ availability, and success of the latter is negatively impacted upon by tissue loss post-transplantation and limited potential for expansion of beta cells. A way to overcome the supply and expansion problems is to xenotransplant embryonic tissue. Previously, we have shown that beta cells originating from embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of streptozotocin-diabetic (type 1) Lewis rats engraft without the need for host immune-suppression and normalize glucose tolerance. Here we show long-term engraftment of pig beta cells within liver, pancreas and mesenteric lymph nodes post-transplantation of E28 pig pancreatic primordia into diabetic ZDF rats, a model for type 2 diabetes. Porcine insulin is present in circulation after an oral glucose load. Glucose tolerance is normalized in transplanted ZDF hosts and insulin sensitivity restored in formerly diabetic ZDF males. Release of porcine insulin in vitro from tissue originating in transplanted rats occurs within 1 min of glucose stimulation characteristic of first-phase secretion from beta cells. Of potential importance for application of this transplantation technology to treatment of type 2 diabetes in humans and confirmatory of our previous findings in Lewis rats, no host immunosuppression is required for engraftment of E28 pig pancreatic primordia.
- Subjects :
- Animals
Diabetes Mellitus, Type 2 blood
Electrophoretic Mobility Shift Assay
Embryo, Mammalian
Female
In Situ Hybridization
Insulin blood
Insulin metabolism
Insulin Secretion
Liver cytology
Liver metabolism
Lymph Nodes cytology
Lymph Nodes metabolism
Male
Mesentery cytology
Mesentery metabolism
Pancreas cytology
Pancreas metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction
Swine
Blood Glucose physiology
Diabetes Mellitus, Type 2 prevention & control
Islets of Langerhans Transplantation methods
Stem Cell Transplantation methods
Transplantation, Heterologous methods
Subjects
Details
- Language :
- English
- ISSN :
- 0966-3274
- Volume :
- 16
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Transplant immunology
- Publication Type :
- Academic Journal
- Accession number :
- 17138051
- Full Text :
- https://doi.org/10.1016/j.trim.2006.08.007