Relationship between changes in glucose production and gluconeogenesis during mild hypoglycemia in humans

We measured 14C-alanine conversion to 14C-glucose (an index of gluconeogenesis) and glucose production in six healthy volunteers during low-dose insulin infusion (0.3 mU/kg.min for four hours). Insulin rose from 7 +/- 2 to 20 +/- 2 microU/mL, and plasma glucose fell to a plateau of 65 to 70 mg/dL after 60 minutes. Glucagon and catecholamines increased after 60 minutes, whereas C-peptide decreased immediately. Glucose production decreased transiently by 43% and then returned to baseline after 45 minutes. In contrast, 14C-alanine conversion to 14C-glucose was unchanged for 120 minutes, but then rose twofold above baseline by 240 minutes. Our data suggest that early recovery of glucose production during mild hyperinsulinemia occurs independent of changes in gluconeogenesis. However, gluconeogenesis plays an increasingly more important role in maintaining glucose production when mild hypoglycemia is prolonged.