A COMBINED BIOCHEMICAL AND HISTOLOGICAL STUDY ON THE ISLETS OF LANGERHANS IN THE GENETICALLY OBESE HYPERGLYCAEMIC MOUSE AND IN THE LEAN MOUSE, INCLUDING OBSERVATIONS ON THE EFFECTS OF STREPTOZOTOCIN TREATMENT

Abstract

SUMMARY The biochemical parameters of blood glucose, serum insulin and pancreatic insulin and glucagon were determined after single injections of the diabetogenic agent streptozotocin and in untreated animals from a strain of genetically obese mice and their lean litter-mates. Histological observations on α and β islet cells were also made in these animals by employing the phosphotungstic acid—haematoxylin and aldehyde—fuchsin staining techniques. In untreated obese mice, endocrine hyperactivity was indicated by the presence of exceptionally large, highly vascular islets and by duct cell-islet metaplasia. After streptozotocin injection, approximately half of the lean mice showed extensive β-cell necrosis and these animals became hyperglycaemic and hypoinsulinaemic with a much reduced pancreatic insulin over a long term. The remaining treated lean mice, whose biochemical parameters did not differ significantly from normal, showed little or no evidence of islet damage. The response of obese mice to streptozotocin treatment was less clear-cut than that of lean animals. Essentially similar histological changes were observed, though these were not consistently correlated with biochemical data. There was histological and biochemical evidence of islet cell recovery from the effects of the drug both in lean and in obese mice, and in all hyperglycaemic animals with initial severe islet damage a marked α-cell response was observed, namely an increased proportion of α cells and their random deployment throughout the islets.