Tilapia islet grafts are highly alloxan-resistant

We have previously shown that dose-response studies performed in streptozotocin (STZ)-diabetic nude mouse recipients bearing established, functioning islet xenografts can be used to directly compare in vivo STZ-sensitivity between donor species and that tilapia (fish) islet grafts are exceedingly STZ-resistant. Using this method, we tested whether tilapia islets are sensitive to alloxan. Tilapia or rat islets were transplanted under the renal capsules of STZ-diabetic nude mice. Recipients with normal glucose tolerance tests (GTTs) on day 30-35 were injected with increasing i.v. doses of alloxan and blood glucose levels were followed for 5-7 days and then GTTs were repeated. Next, mice were killed and their grafts/native pancreata examined histologically (including insulin stains). Control nude mice were also injected with increasing i.v. doses of alloxan. Based upon non-fasting blood glucose levels, GTT, and graft histology, the following observations were made: (1) Tilapia islet xenografts were uniformly resistant to i.v. doses of 75 mg/kg (n=3), 150 mg/kg (n=4), and 300 mg/kg (n=3). (2) Rat islet recipients became uniformly severely diabetic after alloxan i.v. doses of 50-70 mg/kg (n=6) (i.e., equivalent to the dosage needed to induce diabetes in rats). (3) Control nude mice were severely diabetic at doses of 75 mg/kg (4/5) and 150 mg/kg (n=3/3). Alloxan dose-response studies were also performed in tilapia. Interestingly, tilapia appeared more sensitive than tilapia islet grafts. Although 75 mg/kg i.v. had little effect in tilapia, higher doses caused severe beta cell necrosis, diabetes, and systemic damage; however, this seeming discrepancy can be explained as tilapia have about one-quarter of the blood volume of mice (i.e., as a percentage of body weight) and so the actual concentration in the blood was about 4-fold higher at each dose. We conclude that tilapia beta cells are highly resistant to the beta cell toxin alloxan.