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.
Xu
Bao-You
BY
Department of Pathology, IWK Health Centre and Dalhousie University, Halifax, NS, Canada B3H 1V7.
Morrison
Carol M
CM
Yang
Hua
H
Wright
James R
JR
D000496:Alloxan / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D004351:Drug Resistance; D005880:Gills / Q000187:drug effects / Q000473:pathology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D011920:Rats, Inbred WF; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D017210:Tilapia; D014183:Transplantation, Heterologous
D007328:Insulin; D000496:Alloxan