GLYCOGEN ACCUMULATION IN THE NERVES AND KIDNEY OF CHRONICALLY DIABETIC RATS - QUANTITATIVE ELECTRON-MICROSCOPIC STUDY

Deposits of glycogen and related polysaccharides occur in the axons of chronically diabetic rats. Intramitochondrial deposits of glycogen are not unique to diabetes; they have been described in the axons in several toxic neuropathies, but in chronically diabetic rats they are associated with filamentous asteroid inclusions closely resembling Lafora bodies and the inclusions of glycogenosis type IV. These large deposits of glycogen are bounded by the outer membrane of the mitochondrion which appears to degenerate as the glycogen undergoes metamorphosis to Lafora bodies. In this study electron microscopic histochemistry and quantitative electron microscopic analysis were used to identify these structures, to define their structural inter-relationship and to assess their incidence. Both the asteroid inclusions and glycogen granules stained positively with silver proteinate indicating their common polysaccharide composition. Numerous 4 to 6 nanometer filaments were interspersed among glycogen granules and these filaments massed to form the Lafora-body like structures which were often confluent with large glycogen deposits. The incidence of these inclusions was assessed by performing a quantitative electron microscopic examination on randomly selected sections of sciatic nerve from 8 chronically alloxan diabetic rats and 8 age matched controls. Randomly selected blocks from test animals and controls were coded to ensure ‘double blind’ analysis of electron micrographs and sixteen randomly selected, low power fields were examined from each of the 16 rats. Membrane- bounded glycogen deposits were found both in age-matched controls and in diabetics but were twice as common in the axons of diabetic rats. Lafora bodylike inclusions were identified in material from most of the diabetic rats but were not encountered in the age matched controls. These observations were compared to electron microscopic findings in the kidney and which massive glycogen accumulation in renal tubular cells is a well known pathologic feature of diabetes. The significance of intraaxonal glycogen and polyglucosans and their possible relationship to chronic hyperglycemia is discussed. © 1979 American Association of Neuropathologists, Inc.