Differential sensitivity of GLUT1- and GLUT2-expressing beta cells to streptozotocin.
Streptozotocin injection in animals destroys pancreatic beta cells, leading to insulinopenic diabetes. Here, we evaluated the toxic effect of streptozotocin (STZ) in GLUT2(-/-) mice reexpressing either GLUT1 or GLUT2 in their beta cells under the rat insulin promoter (RIPG1 x G2(-/-) and RIPG2 x G2(-/-) mice, respectively). We demonstrated that injection of STZ into RIPG2 x G2(-/-) mice induced hyperglycemia (>20 mM) and an approximately 80% reduction in pancreatic insulin content. In vitro, the viability of RIPG2 x G2(-/-) islets was also strongly reduced. In contrast, STZ did not induce hyperglycemia in RIPG1 x G2(-/-) mice and did not reduce pancreatic insulin content. The viability of in vitro cultured RIPG1 x G2(-/-) islets was also unaffected by STZ. As islets from each type of transgenic mice were functionally indistinguishable, these data strongly support the notion that STZ toxicity toward beta cells depends on the expression of GLUT2.
Hosokawa
M
M
Institute of Pharmacology and Toxicology, 27, rue du Bugnon, Lausanne, CH-1005, Switzerland.
Dolci
W
W
Thorens
B
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D015870:Gene Expression; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D013045:Species Specificity; D013311:Streptozocin / Q000633:toxicity*
D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; C495678:Slc2a1 protein, mouse; C495679:Slc2a1 protein, rat; D013311:Streptozocin