THE ENDOCRINE PANCREAS IN EARLY ALLOXAN DIABETES

Abstract

Starved animals were sensitive to alloxan, whereas a more or less inhibitory effect towards alloxan was observed in fed animals, and in starved animals pretreated with glucose, mannose or fructose, but not in those pretreated with galactose. The islets of starved controls possessed larger B-cell mitochondria than those of fed ones. The earliest B-cell changes in the alloxan-treated animals were localized to the mitochondria which showed swelling, and disruption of inner and occasionally outer membranes. Later, many mitochondria were disintegrated, and the endoplasmic reticulum and Golgi complex disorganized. The secretory granules were preserved, although sometimes with atypical configuration, in degenerating but non-necrotic B-cells, suggesting that insulin stored in granules is not released until the cells are necrotic. Finally, frank necrosis was seen in some B-cells, whereas others were unaffected. The Ca2+-precipitation studied by pyroantimonate technique and x-ray analysis differed in the B-cells of the alloxan-treated animals from that in the controls; the former animals exhibited no or only sparse precipitation in mitochondria and secretory granules, but a rich precipitation in the cytoplasmic ground substance, whereas the precipitation in the controls mainly was localized to mitochondria and secretory granules. The primary site of alloxan action in the B-cells is believed to be localized to the mitochondria.