KATP channel-deficient pancreatic β-cells are streptozotocin resistant because of lower GLUT2 activity

In wild-type mice, a single injection of streptozotocin (STZ, 200 mg/kg body wt) caused within 4 days severe hyperglycemia, hypoinsulinemia, significant glucose intolerance, loss of body weight, and the disappearance of pancreatic β-cells. However, in ATP-sensitive K+ channel (KATP channel)-deficient mice (Kir6.2−/− mice), STZ had none of these effects. Exposing isolated pancreatic islets to STZ caused severe damage in wild-type but not in Kir6.2−/− islets. Following a single injection, plasma STZ levels were slightly less in Kir6.2−/− mice than in wild-type mice. Despite the difference in plasma STZ, wild-type and Kir6.2−/− liver accumulated the same amount of STZ, whereas Kir6.2−/− pancreas accumulated 4.1-fold less STZ than wild-type pancreas. Kir6.2−/− isolated pancreatic islets also transported less glucose than wild-type ones. Quantification of glucose transporter 2 (GLUT2) protein content by Western blot using an antibody with an epitope in the extracellular loop showed no significant difference in...