Intravenous infusion of 30 gm. of L-arginine over a period of 45 minutes elicited a biphasic insulin response and a moderate blood glucose rise in normal subjects. In patients with hyperthyroidism, both insulin peaks, especially the second one, were low, with virtual absence of the blood glucose response. A single intravenous injection of 4 gm. of arginine provoked similar uniphasic plasma insulin responses in both normal subjects and hyperthyroid patients. Pretreatment with either glucose or xylitol almost completely restored the biphasic insulin response to arginine in patients with hyperthyroidism, whereas pretreatment with aminophylline only partially improved the insulin response. Combined administration of a small amount of glucose (2.25 mg./kg./min.) with arginine also restored the normal second-phase insulin release, with blood glucose rises similar to those in normal subjects given arginine alone. It is concluded that the plasma insulin response to arginine is impaired, especially in its second phase, in patients with hyperthyroidism due to the absence of a blood glucose rise. The second phase of arginine-induced insulin release seems more dependent on glucose than the first phase.

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