Effects of Acute Insulin Excess and Deficiency on Gluconeogenesis and Glycogenolysis in Type 1 Diabetes

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Abstract
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.