In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 294, No. 2 ( 2008-02), p. E326-E335
Abstract:
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 (K ATP 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 GLUT2 content between wild-type and Kir6.2 −/− pancreatic islets. However, visualization by immunofluorescence with the same antibody gave rise to 32% less fluorescence in Kir6.2 −/− pancreatic islets. The fluorescence intensity using another antibody, with an epitope in the COOH terminus, was 5.6 times less in Kir6.2 −/− than in wild-type pancreatic islets. We conclude that 1) Kir6.2 −/− mice are STZ resistant because of a decrease in STZ transport by GLUT2 in pancreatic β-cells and 2) the decreased transport is due to a downregulation of GLUT2 activity involving an effect at the COOH terminus.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00296.2007
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
1477331-4
SSG:
12
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