Use of Streptozotocin in Rodent Models of Islet Transplantation

Streptozotocin (STZ) selectively destroys beta cells and is widely used to induce experimental diabetes in rodents. Rodent beta cells are very sensitive to the toxic effects of STZ, while human beta cells are highly resistant to STZ. Taking advantage of this characteristic, here, we describe two protocols for the induction of STZ-diabetes. In the first model, hyperglycemia is induced prior to islet transplantation, whereas in the second model, STZ is injected after islet transplantation. The former model has many applications and thus is the most commonly used method. However, when implanting human islets into mice, there are clear benefits to administering STZ after the transplantation. It reduces the cost and burden of experiments and the number of human islets needed for transplantation and improves the welfare and survival of animals used in the experiments. In both methods, a key step in the experimental protocol is to remove the graft-bearing kidney at the end of the experiment and monitor onset of hyperglycemia. This can be used to demonstrate that the glycemic control of the animal is due to the engrafted islets and not regeneration of endogenous beta cells. This chapter outlines protocols of administering streptozotocin pre- and post-islet transplantation in mice as well as nephrectomy to remove the graft-bearing kidney.