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Uptake of Labeled Alloxan in Mouse Organs and Mitochondria in Vivo and in Vitro^*

Institute of Pathology and Department of Orthopaedic Surgery, University of Umea S-901 87 Umea, Sweden

Address requests for reprints to: Prof. L. Boquist, Institute of Pathology, University of Umea, S-901 87 Umea, Sweden.

Abstract

[¹⁴C]₂-Alloxan was administered in vivo and in vitro for study of the uptake of alloxan in different organs and their mitochondria of mice. After in vivo administration, radioactivity was demonstrated in all organs investigated, with quantitative differences: endocrine pancreas > liver > exocrine pancreas and heart. No significant difference was found between the iv and ip routes of injection. An in vivo uptake of alloxan was also found in mitochondria, with significant quantitative differences as to the origin of the organelles: endocrine pancreas > liver > exocrine pancreas and heart. Pretreatment with Dglucose caused significantly decreased uptake in liver, exocrine pancreas, and heart, but significantly increased uptake in endocrine pancreas, whereas the uptake was significantly decreased in the mitochondria from all of these organs. In vitro uptake was observed in all kinds of mitochondria studied. This uptake was higher than the in vivo uptake in mitochondria from liver, exocrine pancreas, and heart, whereas the uptake in vivo was higher than the in vitro uptake in islet mitochondria. The presence of D-glucose did not affect the in vitro uptake of alloxan in mitochondria. The findings show that in vivo, alloxan passes across plasma membranes and is taken up by mitochondria, and data obtained with mitochondrial subfractions may also indicate a passage across mitochondrial membranes. D-Glucose protection against alloxan diabetogenicity may be associated with prevention of mitochondrial uptake of alloxan. This prevention seems to be dependent on the metabolism of glucose. (Endocrinology 113:943,1983)

Footnotes

^* This work was supported by grants from the Swedish Medical Research Council (Project 12X-5939), the Swedish Diabetes Association, and the Nordic Insulin Fund. Preliminarily reported to the 17th Annual Meeting of the European Association for the Study of Diabetes, Amsterdam, September 15–18,1981.

Received June 1, 1982.