Surviving native beta-cells determine outcome of syngeneic intraportal islet transplantation

In moderately diabetic rats (plasma glucose 20-30 mmol/L), where there is s ome residual pancreatic islet function, normoglycemia can be restored by tr ansplantation of pancreatic islets into the liver via the portal vein. To e xamine whether normoglycemia can also be achieved in more severely diabetic animals (which more closely resemble human type I diabetes), we have compa red the effect of transplanting 1000 islets intraportally in Lewis rats mad e 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 1 28 +/- 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 (fallin g from 290 +/- 5 to 265 +/- 5 g at 1 week and 253 +/- 6 g at 3 weeks). In c ontrast, 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 r ise in plasma glucose (30 +/- 1.3 mmol/L at 1 week, 49 +/- 4 mmol/L at 2 we eks, 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). Fo llowing islet transplantation, nonfasting plasma glucose normalized in mode rately diabetic rats (10.5 +/- 0.6 vs. 9.1 +/- 0.6 mmol/L in nondiabetic co ntrols, NS) after 23 +/- 5 days. In contrast, in the severely diabetic rats plasma glucose stabilized at 32 +/- 5mmol/L (p < 0.05 compared to moderate ly diabetic group) but did not normalize. This difference was not attributa ble to different plasma glucose levels at the time of transplantation (35,1 , 1.8 in moderately diabetic vs. 32.5 <plus/minus> 2.5 mmol/L in severely d iabetic rats). These observations demonstrate that residual native beta -ce lls (equivalent to only 60-80 islets) contribute to the survival or functio n of intraportally transplanted islets.