Streptozotocin (SZ) given in five low doses causes diabetes and an associated lymphocytic infiltration of the pancreatic islets. Using C57BL/KsJ-mice, we demonstrate a reduction in islet number (−38%) and volume (−64%) within 1 day following the last injection of SZ. A substantial fall of insulin secretory capacity (−84%) in the in vitro perfused pancreas matches the reduction in islet cell volume. The parameters of decreased islet function seem to precede the peak of lymphocytic infiltration, occurring 3 days after the last dose of SZ. These functional changes are readily demonstrable before a rise in fasting blood glucose, but they seem to be reflected more readily by a rise in nonfasting blood glucose levels. With development of overt diabetes, as measured by elevated fasting and nonfasting glucose levels, the measures of islet volume and function are reduced to levels only 1–2% of those found in control mice. Taken together, these observations reflect a rapid, islet-toxic effect of SZ that substantially decreases insulin secretory capacity. When islet function falls more than 90%, blood glucose levels begin to reflect the pathophysiologic process. In many aspects, the low-dose SZ model of diabetes parallels the development of diabetes in man. If so, measures other than blood sugar must be developed to identify at an early stage processes reducing islet volume and function.
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May 01 1981
A Major Loss in Islet Mass and B-cell Function Precedes Hyperglycemia in Mice Given Multiple Low Doses of Streptozotocin
Vagn Bonnevie-Nielsen;
Vagn Bonnevie-Nielsen
Hagedorn Research Laboratory
DK-2820 Gentofte, Denmark
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Michael W Steffes;
Michael W Steffes
Hagedorn Research Laboratory
DK-2820 Gentofte, Denmark
Department of Laboratory Medicine and Pathology, University of Minnesota, School of Medicine
Minneapolis, Minnesota
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Åke Lernmark
Åke Lernmark
Hagedorn Research Laboratory
DK-2820 Gentofte, Denmark
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Address reprint requests to Åke Lernmark, Hagedorn Research Laboratory, Niels Steensensvej 6, DK, 2820 Gentofte, Denmark.
Citation
Vagn Bonnevie-Nielsen, Michael W Steffes, Åke Lernmark; A Major Loss in Islet Mass and B-cell Function Precedes Hyperglycemia in Mice Given Multiple Low Doses of Streptozotocin. Diabetes 1 May 1981; 30 (5): 424–429. https://doi.org/10.2337/diab.30.5.424
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