Contributions of gluconeogenesis and glycogenolysis during glucose counterregulation in normal humans

L. Lecavalier, G. Bolli, P. Cryer, J. Gerich

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To estimate the relative contributions of gluconeogenesis and glycogenolysis to the increase in hepatic glucose output (HGO) during glucose counterregulation under conditions simulating clinical insulin hypoglycemia, we induced moderate hypoglycemia (~55 mg/dl) with a continuous infusion of insulin that resulted in physiological hyperinsulinemia (~20 μU/ml) in eight normal volunteers and estimated gluconeogenesis by two methods: an isotopic approach in which appearance of plasma glucose derived from lactate was determined and another approach in which we infused alcohol along with insulin to block gluconeogenesis and used to exogenous glucose required to prevent greater hypoglycemia as an index of gluconeogenesis. Both methods gave similar results. Initially glycogenolysis accounted for ~85% of HGO; however, once hypoglycemia became established, the contribution of gluconeogenesis increased progressively to 77 ± 10 (isotopic method) and 94 ± 10% (alcohol method) of overall HGO. We conclude that in normal humans during moderate protracted hypoglycemia induced by physiological hyperinsulinemia, gluconeogenesis is the predominant factor responsible for the counterregulatory increase in HGO and that increased gluconeogenesis rather than increased glycogenolysis is the primary mechanism preventing development of greater hypoglycemia.

Original languageEnglish
Pages (from-to)19/6
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number6
StatePublished - Jan 1 1989
Externally publishedYes

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