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Unlike mice, dogs exhibit effective glucoregulation during low-dose portal and peripheral glucose infusion

Department of Molecular Physiology and Biophysics and Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee

Submitted 28 July 2003 ; accepted in final form 29 September 2003

Portal infusion of glucose in the mouse at a rate equivalent to basal endogenous glucose production causes hypoglycemia, whereas peripheral infusion at the same rate causes significant hyperglycemia. We used tracer and arteriovenous difference techniques in conscious 42-h-fasted dogs to determine their response to the same treatments. The studies consisted of three periods: equilibration (100 min), basal (40 min), and experimental (180 min), during which glucose was infused at 13.7 µmol· kg^–1·min^–1 into a peripheral vein (PE, n = 5) or the hepatic portal (PO, n = 5) vein. Arterial blood glucose increased 0.8 mmol/l in both groups. Arterial and hepatic sinusoidal insulin concentrations were not significantly different between groups. PE exhibited an increase in nonhepatic glucose uptake (non-HGU; 8.6 ± 1.2 µmol·kg^–1·min^–1) within 30 min, whereas PO showed a slight suppression (–3.7 ± 3.1 µmol·kg^–1·min^–1). PO shifted from net hepatic glucose output (NHGO) to uptake (NHGU; 2.5 ± 2.8 µmol·kg^–1·min^–1) within 30 min, but PE still exhibited NHGO (6.0 ± 1.9 µmol·kg^–1·min^–1) at that time and did not initiate NHGU until after 90 min. Glucose rates of appearance and disappearance did not differ between groups. The response to the two infusion routes was markedly different. Peripheral infusion caused a rapid enhancement of non-HGU, whereas portal delivery quickly activated NHGU. As a result, both groups maintained near-euglycemia. The dog glucoregulates more rigorously than the mouse in response to both portal and peripheral glucose delivery.

hypoglycemia; hyperglycemia; portal vein; glucosensor

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