Surviving Native β-Cells Determine Outcome of Syngeneic Intraportal Islet Transplantation
Abstract:In moderately diabetic rats (plasma glucose 20–30 mmol/L), where there is some residual pancreatic islet function, normoglycemia can be restored by transplantation of pancreatic islets into the liver via the portal vein. To examine whether normoglycemia can also be achieved in more severely diabetic animals (which more closely resemble human type I diabetes), we have compared the effect of transplanting 1000 islets intraportally in Lewis rats made moderately diabetic (55 mg/kg streptozotocin injected IP while nonfasting) or severely diabetic (65 mg/kg streptozotocin injected IP while fasting). In the moderately diabetic rats in which residual pancreatic insulin was 128 ±- 40 mU insulin (2.0% of control), plasma glucose stabilized (32 ±- 2.8 mmol/L at 1 week, 34 ±- 2 mmol/L at 3 weeks) as did body weight (falling from 290 ±- 5 to 265 ±- 5 g at 1 week and 253 ±- 6 g at 3 weeks). In contrast, in severely diabetic rats in which residual pancreatic insulin was only 13.5 ±- 4.2 mU insulin (0.21% of control), there was a progressive rise in plasma glucose (30 ±- 1.3 mmol/L at 1 week, 49 ±- 4 mmol/L at 2 weeks, and 67 ±- 7 mmol/L at 3 weeks) and a progressive fall in body weight (from 304 ±- 10 to 260 ±- 5 g by week 1 and to 209 ±- 6 g by week 3). Following islet transplantation, nonfasting plasma glucose normalized in moderately diabetic rats (10.5 ±- 0.6 vs. 9.1 ±- 0.6 mmol/L in nondiabetic controls, NS) after 23 ±- 5 days. In contrast, in the severely diabetic rats plasma glucose stabilized at 32 ±- 5mmol/L (p < 0.05 compared to moderately diabetic group) but did not normalize. This difference was not attributable to different plasma glucose levels at the time of transplantation (35.1 ±- 1.8 in moderately diabetic vs. 32.5 ±- 2.5 mmol/L in severely diabetic rats). These observations demonstrate that residual native β-cells (equivalent to only 60–80 islets) contribute to the survival or function of intraportally transplanted islets.
Document Type: Research Article
Affiliations: 1: †Centre for Nephrology, Royal Free Campus, Royal Free & University College Medical School, London, UK 2: *Department of Endocrinology, Royal Free Campus, Royal Free & University College Medical School, London, UK
Publication date: 2001-02-01
- Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.