Immunoreactive Glucagon Levels in Obese-hyperglycemic (ob/ob) Mice

A series of studies examined the effects of various experimental manipulations on the glucose, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG) levels of eight-week old ob/ob mice and their lean littermates. The levels of serum glucose, IRI, and IRG of ob/ob mice were significantly higher than those of the lean mice in the basal state and remained higher throughout an 18-hour period of fasting. Both groups responded to food deprivation with reduced glucose and IRI concentrations, but the IRG levels of obese mice were reduced by fasting while those of lean mice were marginally elevated. The IRG levels of both phenotypes were reduced to a similar degree by glucose administration, and the serum glucose and IRI responses of the two groups were proportional to their preinjection levels. Arginine treatment increased the IRG and IRI of both groups. Arginine also lowered the glucose levels of lean mice, but, notably, it did not affect the serum glucose of ob/ob mice. The simultaneous administration of arginine and insulin to lean mice potentiated the hyperglucagonemia and hypoglycemia that followed arginine alone, but in ob/ob mice combined treatment increased the glucose concentrations while not affecting IRG. These data indicate that ob/ob mice have several abnormalities in their metabolic-endocrine responses to both food deprivation and to stimulation with metabolically active agents. However, from the present results we could not determine a specific disturbance of IRI or IRG regulation that could account for the persistence of their hyperglucagonemia, hyperinsulinemia, or hyperglycemia.