Effects of acute insulin excess and deficiency on gluconeogenesis and glycogenolysis in type 1 diabetes

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 (2)H(2)O) 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 approximately 4 h with IV glucose. EGP (with 6,6-(2)H glucose) decreased from 17.1 to 9.8 micro mol. 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 micro mol. 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 micro mol/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.