This study investigates the function of pancreatic alpha cells in both non-diabetic and diabetic individuals. A highly specific radioimmunoassay for pancreatic glucagon enabled the evaluation of alpha cell function. In non-diabetic subjects, the mean fasting plasma glucagon level was 108 μg/ml, while in diabetic subjects, it was similar, averaging 110-114 μg/ml. However, when hyperglycemia was induced in non-diabetic subjects, their glucagon levels dropped significantly, suggesting that diabetic subjects may have an inappropriate increase in alpha cell function. Arginine infusion significantly increased glucagon levels in both non-diabetic and diabetic subjects. In non-diabetics, glucagon rose to 331 μg/ml at 40 minutes, while in diabetics, it reached 458-452 μg/ml. This response was not affected by hyperglycemia, indicating that diabetic alpha cells are hyperresponsive to arginine. The study also found that glucagon levels were elevated in some patients with severe diabetic ketoacidosis before insulin treatment. The findings suggest that alpha cell function is inappropriately increased in diabetes, which may contribute to the diabetic syndrome. The study also found that glucagon levels were not influenced by obesity, duration of diabetes, or treatment type. In patients with advanced Kimmelsteil-Wilson disease, glucagon levels were significantly elevated, indicating that alpha cell function is preserved despite pancreatic damage. The study concludes that fasting glucagon levels in both non-diabetic and diabetic subjects average slightly over 100 μg/ml. Induced hyperglycemia in non-diabetics reduced glucagon levels to significantly lower values than in diabetics. Arginine infusion uniformly stimulated glucagon secretion in non-diabetics, while in diabetics, the response was exaggerated despite hyperglycemia. In severe diabetic ketoacidosis, glucagon levels may be extraordinarily high before treatment. The study highlights the importance of alpha cell function in diabetes and suggests that hyperglucagonemia may play a significant role in the diabetic syndrome.This study investigates the function of pancreatic alpha cells in both non-diabetic and diabetic individuals. A highly specific radioimmunoassay for pancreatic glucagon enabled the evaluation of alpha cell function. In non-diabetic subjects, the mean fasting plasma glucagon level was 108 μg/ml, while in diabetic subjects, it was similar, averaging 110-114 μg/ml. However, when hyperglycemia was induced in non-diabetic subjects, their glucagon levels dropped significantly, suggesting that diabetic subjects may have an inappropriate increase in alpha cell function. Arginine infusion significantly increased glucagon levels in both non-diabetic and diabetic subjects. In non-diabetics, glucagon rose to 331 μg/ml at 40 minutes, while in diabetics, it reached 458-452 μg/ml. This response was not affected by hyperglycemia, indicating that diabetic alpha cells are hyperresponsive to arginine. The study also found that glucagon levels were elevated in some patients with severe diabetic ketoacidosis before insulin treatment. The findings suggest that alpha cell function is inappropriately increased in diabetes, which may contribute to the diabetic syndrome. The study also found that glucagon levels were not influenced by obesity, duration of diabetes, or treatment type. In patients with advanced Kimmelsteil-Wilson disease, glucagon levels were significantly elevated, indicating that alpha cell function is preserved despite pancreatic damage. The study concludes that fasting glucagon levels in both non-diabetic and diabetic subjects average slightly over 100 μg/ml. Induced hyperglycemia in non-diabetics reduced glucagon levels to significantly lower values than in diabetics. Arginine infusion uniformly stimulated glucagon secretion in non-diabetics, while in diabetics, the response was exaggerated despite hyperglycemia. In severe diabetic ketoacidosis, glucagon levels may be extraordinarily high before treatment. The study highlights the importance of alpha cell function in diabetes and suggests that hyperglucagonemia may play a significant role in the diabetic syndrome.