Non-insulin-dependent diabetes mellitus (NIDDM) is attributed to a failure of pancreatic β cells to maintain insulin secretion at a level sufficient to compensate for underlying insulin resistance. In the ZDF rat, a model of NIDDM that closely resembles the human syndrome, we have previously reported profound underexpression of GLUT-2, the high-Km facultative glucose transporter expressed by β cells of normal animals. Here we report that islets of diabetic rats exhibit a marked decrease in the volume density of GLUT-2-positive β cells and a reduction at the electron-microscopic level in the number of GLUT-2-immunoreactive sites per unit of β-cell plasma membrane. The deficiency of GLUT-2 cannot be induced in normal β cells by in vivo or in vitro exposure to high levels of glucose nor can it be prevented in β cells of prediabetic ZDF rats by elimination of hyperglycemia. We conclude that this dearth of immunodetectable GLUT-2 in NIDDM is not secondary to hyperglycemia and therefore that it may well play a causal role in the development of hyperglycemia.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1990|
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