Physiological and morphological changes in islet B cells following treatment of the guinea pig with alloxan.

Alloxan injections (200 mg/kg i.v.) into guinea pigs led to a significant decline of serum insulin levels and a marked inhibition of normal weight gain during the first 96 hr following treatment. Both of these parameters tended to normalize between 96 and 120 hr after treatment. However, neither hyperglycemia nor glycosuria occurred at any time. Volume densities of islet B cells (= volume density of islet cells immunostained for insulin per islet volume density) decreased and pyknotic nuclei appeared in the islets during the initial 48 hr after alloxan treatment. Islet B-cell volume density then returned to normal over the ensuing 24 hr, and remained normal up to 120 hr following administration of alloxan. In summary, after high doses of alloxan were given guinea pigs, serum insulin levels were reduced below control levels within 24 hr; this was associated with changes in body weight which paralleled changes in insulin levels more closely than did levels of blood or urine glucose; the volume density of immunostained B cells initially decreased and then returned to control levels by 72 hr following alloxan injection. The alloxan-treated guinea pig may represent a unique model for studying the restoration of insulinogenic capacity in insulinopenic diabetes.