As far as exaggerated arginine-induced glucagon secretion in diabetics is concerned, the authors have shown that both the restoration of blood glucose excursions and physiological insulinemia in response to arginine, obtained from an artificial endocrine pancreas (AEP) could normalize the glucagon secretory responses in diabetes mellitus. To clarify whether or not physiological glycemic excursions and/or plasma insulin profiles contribute to the normalization of the exaggerated glucagon response in diabetes mellitus, the following 4 investigations were conducted on each of 7 non-obese, non-insulin-dependent diabetic (NIDDM), and 8 insulin-dependent diabetic (IDDM) subjects, with the aid of AEP. Arginine was i.v. infused into both diabetic groups (1) in a hyperglycemic state without insulin infusion, (2) in perfect glycemic control with insulin infusion by AEP, (3) in glycemic control with AEP, but with lower plasma insulin profiles (parameters of the insulin infusion algorithm were made smaller than those of (2], (4) in a state where blood glucose levels were clamped at the same levels as obtained in (1) with the aid of glucose infusion controlled by AEP, and where physiological plasma insulin profiles were mimicked by infusing insulin at the same rates used in (2) with a pre-programmable insulin infusion system. The changes in the plasma glucagon (IRG) response in each experiment were compared with those seen in healthy subjects. For both diabetic groups it was found that: in (2) perfect normalization of glucagon response was achieved.(ABSTRACT TRUNCATED AT 250 WORDS)