Nonhepatic response to portal glucose delivery in conscious dogs (original) (raw)
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Journal of Clinical Investigation, 1987
To assess the importance of the route of glucose delivery in determining net hepatic glucose balance (NHGB) eight conscious overnight-fasted dogs were given glucose via the portal or a peripheral vein. NHGB was measured using the arteriovenous difference technique during a control and two 90-min glucose infusion periods. The sequence of infusions was randomized. Insulin and glucagon were held at constant basal levels using somatostatin and intraportal insulin and glucagon infusions during the control, portal, and peripheral glucose infusion periods (7±1, 7±1, 7±1 IU/ml; 100±3, 101±6, 101±3 pg/ml, respectively). In the three periods the hepatic blood flow, glucose infusion rate, arterial glucose level, hepatic glucose load, arterial-portal glucose difference and NHGB were 37±1, 34±1, 32±3 ml/kg per min; 0±0, 4.51±0.57, 4.23±0.34 mg/kg per min; 101±5, 200±15, 217±13 mg/dl; 28.5±3.5, 57.2±6.7, 54.0±6.4 mg/kg per min; +2±1,-22±3, +4±1 mg/dl; and 2.22±0.28,-1.41±031, and 0.08±0.23 mg/kg per min, respectively. Thus when glucose was delivered via a peripheral vein the liver did not take up glucose but when a similar glucose load was delivered intraportally the liver took up 32% (P < 0.01) of it. In conclusion portal glucose delivery provides a signal important for the normal hepatic-peripheral distribution of a glucose load. Methods Animals and surgical procedures. Experiments were carried out on eight overnight-fasted (18 h) conscious dogs (17-22 kg) of either sex that had Route ofGlucose Delivery and Hepatic Glucose Uptake 557 J. Clin. Invest.
Insulin is required for the liver to respond to intraportal glucose delivery in the conscious dog
Diabetes, 1992
To determine whether insulin is essential for the augmented hepatic glucose uptake observed in the presence of intraportal glucose delivery, SRIF was used to induce acute insulin deficiency in 5 conscious dogs, and glucose was infused into the portal vein or a peripheral vein in two sequential, randomized periods. Insulin and C-peptide levels were below the limits of detection after SRIF infusion, and the load of glucose presented to the liver was approximately doubled and equivalent during the portal and peripheral periods. Net hepatic glucose output was 2.9 ± 0.9 and 2.1 ± 1. 1 jimol • kg" 1 • min~1 during portal and peripheral glucose delivery, respectively. In an additional set of protocols, pancreatectomized dogs were used to investigate the effects of prolonged insulin deficiency (n = 5) and acute insulin replacement (n = 4) on the hepatic response to intraportal glucose delivery. In the prolonged insulin deficiency protocol, SRIF was used to lower glucagon and thereby reduce circulating glucose levels, and glucose was infused into the portal or peripheral circulations in two sequential, randomized periods. As with acute insulin deficiency, net hepatic glucose output was still evident and similar (3.6 ± 1. 1 and 4.2 ± 1. 3 junol • k g 1 • min" 1) during portal and peripheral glucose delivery, respectively. When the pancreatectomized dogs were restudied using a similar protocol, but one in which insulin was replaced (4X-basal), and the glucose load to the liver was matched to that which occurred in the prolonged insulin deficiency protocol, net hepatic glucose uptake was 23.6 ± 6.1 jimol • kg" 1 • mirr 1 during portal glucose delivery but only 10.3 ± 3.5
Impact of portal glucose delivery on glucose metabolism in conscious, unrestrained mice
American Journal of Physiology-Endocrinology and Metabolism, 2006
Previous studies in mice suggest that portal venous infusion of glucose at a low rate paradoxically causes hypoglycemia; this does not occur in dogs, rats, and humans. A possible explanation is that fasting status in the mouse studies may have altered the response. We sought to determine whether the response to portal glucose delivery in the mouse was similar to that seen in other species and whether it was dependent on fasting status. Studies were performed on chronically catheterized conscious mice. Catheters were placed into the portal and jugular veins and carotid artery 5 days before study. After a 5- or 16-h fast, glucose was infused into either the portal (PO) or the jugular vein (JU) for 6 h at 25 μg·g−1·min−1. [3-3H]glucose was infused into the JU to measure glucose turnover. In 5-h-fasted mice, PO and JU exhibited similar increases in arterial blood glucose from 155 ± 11 to 173 ± 19 and 147 ± 8 to 173 ± 10 mg/dl, respectively. Endogenous glucose production decreased and ar...
Portal glucose infusion increases hepatic glycogen deposition in conscious unrestrained rats
Journal of Applied …, 1999
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
Diabetes, 2005
The results of the present study, using the conscious beagle dog, demonstrate that inhaled insulin (INH; Exubera) provides better glycemic control during an intraportal glucose load than identical insulin levels induced by insulin (Humulin) infusion into the inferior vena cava (IVC). In the INH group (n = 13), portal glucose infusion caused arterial plasma glucose to rise transiently (152 ± 9 mg/dl), before it returned to baseline (65 min) for the next 2 h. Net hepatic glucose uptake was minimal, whereas nonhepatic uptake rose to 12.5 ± 0.5 mg · kg−1 · min−1 (65 min). In the IVC group (n = 9), arterial glucose rose rapidly (172 ± 6 mg/dl) and transiently fell to 135 ± 13 mg/dl (65 min) before returning to 165 ± 15 mg/dl (125 min). Plasma glucose excursions and hepatic glucose uptake were much greater in the IVC group, whereas nonhepatic uptake was markedly less (8.6 ± 0.9 mg · kg−1 · min−1; 65 min). Insulin kinetics and areas under the curve were identical in both groups. These data...