Portal glucose infusion increases hepatic glycogen deposition in conscious unrestrained rats (original) (raw)

1999, Journal of Applied …

It has been demonstrated in the conscious dog that portal glucose infusion creates a signal that increases net hepatic glucose uptake and hepatic glycogen deposition. Experiments leading to an understanding of the mechanism by which this change occurs will be facilitated if this finding can be reproduced in the rat. Rats weighing 275-300 g were implanted with four indwelling catheters (one in the portal vein, one in the left carotid artery, and two in the right jugular vein) that were externalized between the scapulae. The rats were studied in a conscious, unrestrained condition 7 days after surgery, following a 24-h fast. Each experiment consisted of a 30-to 60-min equilibration, a 30-min baseline, and a 120-min test period. In the test period, a pancreatic clamp was performed by using somatostatin, insulin, and glucagon. Glucose was given simultaneously either through the jugular vein to clamp the arterial blood level at 220 mg/dl (Pe low group) or at 250 mg/dl (Pe high group), or via the hepatic portal vein (Po group; 6 mg•kg Ϫ1 •min Ϫ1) and the jugular vein to clamp the arterial blood glucose level to 220 mg/dl. In the test period, the arterial plasma glucagon and insulin levels were not significantly different in the three groups (36 Ϯ 2, 33 Ϯ 2, and 30 Ϯ 2 pg/ml and 1.34 Ϯ 0.08, 1.37 Ϯ 0.18, and 1.66 Ϯ 0.11 ng/ml in Po, Pe low, and Pe high groups, respectively). The arterial blood glucose levels during the test period were 224 Ϯ 4 mg/dl for Po, 220 Ϯ 3 for Pe low, and 255 Ϯ 2 for Pe high group. The liver glycogen content (µmol glucose/g liver) in the two Pe groups was not statistically different (51 Ϯ 7 and 65 Ϯ 8, respectively), whereas the glycogen level in the Po group was significantly greater (93 Ϯ 9, P Ͻ 0.05). Because portal glucose delivery also augments hepatic glycogen deposition in the rat, as it does in the dogs, mechanistic studies relating to its function can now be undertaken in this species. liver; somatostatin; insulin; glucagon; portal signal THE LIVER IS ONE OF THE KEY ORGANS in glucose homeostasis. Whereas a great deal is known about the liver as a producer of glucose, much less is known about its role in glucose disposal. It remains unclear exactly how hepatic glucose uptake is regulated after oral glucose consumption, when the blood glucose and insulin levels rise and the glucagon level falls. Based on work carried out in humans (11, 12) and in dogs (14, 18), it is clear that neither hyperinsulinemia nor hyperglycemia, when