Guinea pigs injected with streptozotocin were significantly hyperglycemic on day 1 after injection but only mildly so on day 14. However, serum insulin levels were significantly depressed on day 14; at this time the animals had lost 25% of their initial body weights and were severely glycosuric. The volume fraction of inimunostainable B cells in the pancreas was reduced to one third of control values by day 1 after injection and remained at this level by day 14. Animals thai received alloxan were slightly hyperglycemic on day 1 but not on day 14. Both serum insulin and volume fraction of B cells in the pancreas were reduced by 70% on day 1 but had returned to control levels by day 14. Body weights for this group were equivalent to controls at both time points. These data indicate that (1) streptozotocin treatment of guinea pigs causes a diabetes-like condition characterized by insulin deficiency, pancreatic B cell loss, glycosuria, and weight loss, which are not reversed in the first 2 weeks after injection, whereas hyperglycemia is only transitory; ( 2 ) alloxan also produces a diabetes-like condition early after injection, but all signs of diabetes disappear within 2 weeks, by which time serum insulin levels and the volume fraction of B cells in the pancreas have returned to normal. The experimental results suggest that regeneration of islet B cells following destruction by alloxan may be the primary cause of the recovery of alloxan-injected guinea pigs from the effects of the drug, whereas the persistence of insulin deficiency is consistent with an absence of islet B cell regeneration in the streptozotocin-treated animals.

Cell types containing insulin, glucagon, somatostatin, and pancreatic polypeptide were identified in guinea pig islets with light and electron microscopic immunoperoxidase staining. Cells containing immunostainable insulin (B cells) are located throughout the islets, including the islet periphery, and contain irregularly shaped granules (350-550 nm). Granule contents are of variable opacity and are often fragmented but not crystalloid. Cells containing immunoreactive glucagon (A cells) are found in the interior of islets and contain numerous spheroid electron-opaque granules (250-350 nm). Cells containing immunoreactive somatostatin (D cells) have elongate, axonlike processes that end adjacent to islet capillaries. D cells, which are very numerous and distributed uniformly throughout the islet parenchyma, contain small spheroid granules (150-25 nm) of pale electron opacity. Cells with immunoreactive pancreatic polypeptide (F cells) are rare in islets but numerous among the exocrine parenchyma. F cells contain pale spheroid granules (100-200 nm). Morphological criteria are reliable indicators for A cells and B cells, but D cells and F cells require immunostaining for positive identification.

Quantitative histomorphometric studies of the dynamics of growth and development of pancreatic islets in normal and pathological states pose substantial methodological and conceptual problems. We address these problems with the geometry of random fractals, and apply our methods to the analysis of islet regeneration in the alloxan-treated guinea-pig. In both experimental islet-regenerated and control animals, islet centres are found to cluster in similar fractal subsets of dimension strictly less than 3, in agreement with the postulated origin of islets along a system of ductules, and suggesting that regeneration follows the same mathematical dynamics as original islet formation.