Peripheral effects of insulin dominate suppression of fasting hepatic glucose production

• DOI: 10.1152/ajpendo.1990.258.6.e1020
• Publication Date: 2017-12-22T04:23:20Z
• Authors: M. Ader; R. N. Bergman
• Keywords: Blood Glucose; Male; 0301 basic medicine; Analysis of Variance; Radioisotope Dilution Technique; Dose-Response Relationship, Drug; Tritium; Kinetics; 03 medical and health sciences; Dogs; Glucose; Insulin Infusion Systems; Liver; Glucose Clamp Technique; Animals; Insulin; Infusions, Intravenous

Insulin may suppress hepatic glucose production directly, or indirectly via suppression of release gluconeogenic substrates from extrasplanchnic tissues. To compare these mechanisms, we performed insulin dose-response experiments in conscious dogs at euglycemia, during somatostatin infusion, and intraportal glucagon replacement. was sequentially infused either intraportally (0.05, 0.20, 0.40, 1.0, 1.4, and/or 3.0; protocol I) systemically half the rate (0.025, 0.10, 0.50, 0.70, 1.5 mU.min-1.kg-1; II). Exogenous clamps labeled with 3-[3H]glucose (2 microCi/g) to prevent a fall plasma specific activity (P greater than 0.2) that have contributed previous underestimations output (HGO). Portal insulins were up threefold higher but peripheral levels not different between systemic protocols [7 +/- 5 vs. 9 1, 12 4 13 6, 16 3 27 5, 70 23 48 8, 83 86 21, 128 120 14 microU/ml for paired doses; P 0.06 by analysis variance (ANOVA)]. Despite portal I, HGO equivalent two when matched, 3.3 0.1 near-total 0.3 mg.min-1.kg-1 highest infusion (3.0 less 0.0001) insulin, 2.9 0.8 -0.8 0.2 II 0.001). Suppression similar matched regardless suggesting primacy insulin's action on periphery its restraint production.