To determine whether insulin induces acute changes in endogenous glucose production (EGP) via changes in gluconeogenesis (GNG), glycogenolysis (GL), or both, we measured GNG (with 2H2O) and GL (EGP-GNG) in nine patients with type 1 diabetes during acute insulin excess produced by subcutaneous injection of insulin and during insulin deficiency which developed between 5 and 8 h after insulin injection. During insulin excess, free insulin concentration rose fivefold (from 36 to 180 pmol/l). Plasma glucose was maintained between 6.2 and 6.7 mmol/l for ∼4 h with IV glucose. EGP (with 6,6-2H glucose) decreased from 17.1 to 9.8 μmol · kg−1 · min−1 after 1 h. This decrease was almost completely accounted for by a decrease in GL (from 10.7 to 4.6 μmol · kg−1 · min−1). During insulin deficiency, plasma glucose rose from 6.2 to 10.5 mmol/l and EGP from 9.5 to 14.3 μmol/kg min. The increase in EGP again was accounted for by an increase in GL.
We conclude that in type 1 diabetes acute regulation of EGP by insulin is mainly via changes in GL while GNG changes little during the early hours of acute insulin excess or deficiency.
Address correspondence and reprint requests to Guenther Boden, Temple University Hospital, 3401 N. Broad St., Philadelphia, PA 19140. E-mail:.
Received for publication 26 July 2002 and accepted in revised form 18 September 2002.
EGP, endogenous glucose production; FFA, free fatty acid; GL, glycogenolysis; GNG, gluconeogenesis; GRa, rate of glucose appearance; GRd, rate of glucose disappearance.