Circulating insulin inhibits glucagon secretion induced by arginine in type 1 diabetes

Objective: To evaluate if insulin has a suppressive effect on the glucagon secretion stimulated by arginine in type 1 diabetes. Research design and methods: The alpha-cell response to an i.v. bolus of ar ginine (150 mg kg(-1)) followed by an infusion of arginine (10 mg kg(-1) mi n(-1)) was studied in random order during either low dose infusion (LDT) or high dose infusion (HDT) of insulin in ten patients with type 1 diabetes. The blood glucose level was clamped at an arterialized level of 5 mmol l(-1 ) by a variable infusion of glucose. Venous C-peptide, glucagon, growth hor mone, and insulin were analyzed. Results: The mean plasma concentration of insulin was four times higher dur ing the HDT, The C-peptide level did not differ between the LDT and the HDT . During the LDT in response to arginine the blood glucose level increased from 5.0 to 5.8 mmol l(-1) although the glucose infusion was markedly reduc ed, while no change was seen during the HDT. A significantly smaller increa se in the glucagon levels during the HDT was seen (area under the curve of 413 +/- 45 vs 466 +/- 44 pg ml(-1) h(-1), P = 0.03) while the growth hormon e levels were almost identical. Conclusion: This study demonstrates that a high level of circulating insuli n exerts an inhibitory effect on the glucagon response to arginine in type 1 diabetes. Thus, the suppressive effect of insulin on the glucagon release from the alpha-cell seems to be general and not only dependent on stimulat ion by hypoglycemia.