THE EFFECT OF PROTRACTED GLUCAGON ADMINISTRATION ON BLOOD GLUCOSE AND ON PANCREATIC MORPHOLOGY1

Abstract

A study was conducted on the effect of long continued administration of glucagon with or without cortisone on blood and urine glucose and on pancreatic morphology in rabbits. One mg of crystalline glucagon was administered subcutaneously 3 times daily at 8 hour intervals either alone or together with 1 mg/kg daily of cortisone acetate intramuscularly. Glucagon alone produced only a moderately increased glycemia. On the other hand, glucagon with cortisone produced a marked hyperglycemic status which generally tended to ameliorate after approximately 6 weeks of treatment. Morphologically, there was in most glucagon treated animals an apparent reduction in the numbers of identifiable pancreatic A cells. In many instances partly degranulated or poorly staining A cells were observed as well as groups of nuclei with ill-defined cytoplasm which resembled the nuclei of identifiable A cells and which were thought to be degranulated A cells. The inference from these A cell changes is that glucagon is a hormone and that it is derived from this cellular system. Additional findings included B cell degranulation and glycogen infiltration of duct epithelium and of B cells. Furthermore, in animals treated for prolonged periods there was B cell hyperplasia as well as neogenesis of these cells from ductular epithelium via primitive B cell formation. These latter morphologic findings support the viewpoint that the diminishing diabetogenic effectiveness of these hormones with prolongation of treatment is due to increased pancreatic insulinogenesis.