Hughes S J, Powis S H, Press M
Department of Endocrinology, Royal Free & University College Medical School, London, UK.
Cell Transplant. 2001 Mar-Apr;10(2):145-51.
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 +/- 5 mmol/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 beta-cells (equivalent to only 60-80 islets) contribute to the survival or function of intraportally transplanted islets.
在中度糖尿病大鼠（血浆葡萄糖20 - 30 mmol/L）中，其胰腺胰岛仍有一定残余功能，通过门静脉将胰岛移植到肝脏可恢复正常血糖水平。为了研究在更严重的糖尿病动物（更类似于人类I型糖尿病）中是否也能实现正常血糖水平，我们比较了将1000个胰岛经门静脉移植到中度糖尿病（非空腹腹腔注射55 mg/kg链脲佐菌素）或重度糖尿病（空腹腹腔注射65 mg/kg链脲佐菌素）的Lewis大鼠中的效果。在中度糖尿病大鼠中，残余胰腺胰岛素为128±40 mU胰岛素（为对照的2.0%），血浆葡萄糖稳定（1周时为32±2.8 mmol/L，3周时为34±2 mmol/L），体重也稳定（1周时从290±5 g降至265±5 g，3周时降至253±6 g）。相比之下，在重度糖尿病大鼠中，残余胰腺胰岛素仅为13.5±4.2 mU胰岛素（为对照的0.21%），血浆葡萄糖持续升高（1周时为30±1.3 mmol/L，2周时为49±4 mmol/L，3周时为67±7 mmol/L），体重持续下降（第1周时从304±10 g降至260±5 g，第3周时降至209±6 g）。胰岛移植后，中度糖尿病大鼠在23±5天后非空腹血浆葡萄糖恢复正常（10.5±0.6 mmol/L，与非糖尿病对照组的9.1±0.6 mmol/L相比，无统计学差异）。相比之下，重度糖尿病大鼠的血浆葡萄糖稳定在32±5 mmol/L（与中度糖尿病组相比，p<0.05），但未恢复正常。这种差异并非归因于移植时不同的血浆葡萄糖水平（中度糖尿病大鼠为35.1±1.8 mmol/L，重度糖尿病大鼠为32.5±2.5 mmol/L）。这些观察结果表明，残余的天然β细胞（仅相当于60 - 80个胰岛）有助于经门静脉移植的胰岛的存活或功能。
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