Streptozotocin-induced diabetes in large animals (pigs/primates): role of GLUT2 transporter and beta-cell plasticity.
BACKGROUND
To induce irreversible diabetes in large animals, the efficiency of streptozotocin (STZ) was evaluated in pigs, primates and compared to the gold standard model in rats.


METHODS
Low (50 mg/kg) and high (150 mg/kg) doses of STZ were tested. Hepatic/renal function, glucose metabolism (intravenous glucose tolerance tests, fasting blood glucose) and histomorphometry were evaluated prior to, 1, and 4 weeks after STZ treatment.


RESULTS
In rats and primates, expressing a high level of GLUT2 expression on beta cells, a dose of 50 mg/kg STZ induced irreversible diabetes (due to the 97% destruction of beta cell mass) without provoking liver or renal failure. In pigs, despite the use of high STZ dose, partial correction of hyperglycaemia was observed four weeks after STZ injection (decreased fasting blood glucose and intravenous glucose tolerance tests; increased insulin production). The correction of hyperglycaemia was associated with significant hypertrophy of immature pig beta-cell clusters (+30%, P<0.05), whereas no hypertrophy was observed in rats/primates.


CONCLUSIONS
These results demonstrated that STZ might be used to induce irreversible diabetes in rats and primates. In contrast, the low STZ sensitivity in pigs related to a low expression of GLUT2, higher number of immature beta cells and compensatory beta-cell hypertrophy, renders STZ-induced diabetes inappropriate for studying islet allografts in swine.
Dufrane
Denis
D
Laboratory of Experimental Surgery, Université catholique de Louvain, Faculté de Médecine, Brussels, Belgium.
van Steenberghe
Mathieu
M
Guiot
Yves
Y
Goebbels
Rose-Marie
RM
Saliez
Alain
A
Gianello
Pierre
P
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D011323:Primates / Q000378:metabolism*; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology*; D013552:Swine / Q000378:metabolism*
D051273:Glucose Transporter Type 2; D013311:Streptozocin; D005947:Glucose