Importance of the hepatic arterial glucose level in generation of the portal signal in conscious dogs

2000 ◽  
Vol 279 (2) ◽  
pp. E284-E292 ◽  
Author(s):  
Po-Shiuan Hsieh ◽  
Mary Courtney Moore ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Glucose Uptake ◽  
Hepatic Artery ◽  
Glucose Level ◽  
Test Period ◽  
Conscious Dogs ◽  
Control Group ◽  
Period 2 ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Arterial Glucose

The aim of this study was to determine whether the elimination of the hepatic arterial-portal (A-P) venous glucose gradient would alter the effects of portal glucose delivery on hepatic or peripheral glucose uptake. Three groups of 42-h-fasted conscious dogs ( n = 7/group) were studied. After a 40-min basal period, somatostatin was infused peripherally along with intraportal insulin (7.2 pmol·kg−1·min−1) and glucagon (0.65 ng·kg−1·min−1). In test period 1 (90 min), glucose was infused into a peripheral vein to double the hepatic glucose load (HGL) in all groups. In test period 2 (90 min) of the control group (CONT), saline was infused intraportally; in the other two groups, glucose was infused intraportally (22.2 μmol·kg−1·min−1). In the second group (PD), saline was simultaneously infused into the hepatic artery; in the third group (PD+HAD), glucose was infused into the hepatic artery to eliminate the negative hepatic A-P glucose gradient. HGL was twofold basal in each test period. Net hepatic glucose uptake (NHGU) was 10.1 ± 2.2 and 12.8 ± 2.1 vs. 11.5 ± 1.6 and 23.8 ± 3.3* vs. 9.0 ± 2.4 and 13.8 ± 4.2 μmol · kg−1·min−1 in the two periods of CONT, PD, and PD+HAD, respectively (*  P < 0.05 vs. same test period in PD and PD+HAD). NHGU was 28.9 ± 1.2 and 39.5 ± 4.3 vs. 26.3 ± 3.7 and 24.5 ± 3.7* vs. 36.1 ± 3.8 and 53.3 ± 8.5 μmol·kg−1·min−1 in the first and second periods of CONT, PD, and PD+HAD, respectively (*  P < 0.05 vs. same test period in PD and PD+HAD). Thus the increment in NHGU and decrement in extrahepatic glucose uptake caused by the portal signal were significantly reduced by hepatic arterial glucose infusion. These results suggest that the hepatic arterial glucose level plays an important role in generation of the effect of portal glucose delivery on glucose uptake by liver and muscle.

The head arterial glucose level is not the reference site for generation of the portal signal in conscious dogs

1999 ◽  
Vol 277 (4) ◽  
pp. E678-E684 ◽  
Author(s):  
Po-Shiuan Hsieh ◽  
Mary Courtney Moore ◽  
Bess Marshall ◽  
Michael J. Pagliassotti ◽  
Brian Shay ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Level ◽  
Control Period ◽  
Fold Increase ◽  
Test Period ◽  
Conscious Dogs ◽  
Reference Standard ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Arterial Glucose

Experiments were performed on twelve 42-h-fasted, conscious dogs to determine whether the head arterial glucose level is used as a reference standard for comparison with the portal glucose level in bringing about the stimulatory effect of portal glucose delivery on net hepatic glucose uptake (NHGU). Each experiment consisted of an 80-min equilibration, a 40-min control, and two 90-min test periods. After the control period, somatostatin was given along with insulin (7.2 pmol ⋅ kg−1⋅ min−1; 3.5-fold increase) and glucagon (0.6 ng ⋅ kg−1⋅ min−1; basal) intraportally. Glucose was infused intraportally (22.2 μmol ⋅ kg−1⋅ min−1) and peripherally as needed to double the hepatic glucose load. In one test period, glucose was infused into both vertebral and carotid arteries (HEADG; 22.2 ± 0.8 μmol ⋅ kg−1⋅ min−1); in the other test period, saline was infused into the head arteries (HEADS). One-half of the dogs received HEADGfirst. When all dogs are considered, the blood arterial-portal glucose gradients (−0.52 ± 0.07 vs. −0.49 ± 0.03 mM) and the hepatic glucose loads (339 ± 14 vs. 334 ± 20 μmol ⋅ kg−1⋅ min−1) were similar in HEADGand HEADS. NHGU was 24.1 ± 3.8 and 25.1 ± 4.6 μmol ⋅ kg−1⋅ min−1, and nonhepatic glucose uptake was 46.1 ± 4.2 and 48.8 ± 7.0 μmol ⋅ kg−1⋅ min−1in HEADGand HEADS, respectively. The head arterial glucose level is not the reference standard used for comparison with the portal glucose level in the generation of the portal signal.

Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs

2003 ◽  
Vol 284 (5) ◽  
pp. E1027-E1036 ◽  
Author(s):  
Makoto Nishizawa ◽  
Mary Courtney Moore ◽  
Masakazu Shiota ◽  
Stephanie M. Gustavson ◽  
Wanda L. Snead ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Conscious Dogs ◽  
Glucose Disposal ◽  
Control Group ◽  
Hepatic Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Hepatic Glucose Uptake ◽  
Arteriovenous Difference ◽  
Intraportal Infusion

Arteriovenous difference and tracer ([3-3H]glucose) techniques were used in 42-h-fasted conscious dogs to identify any insulin-like effects of intraportally administered glucagon-like peptide 1-(7–36)amide (GLP-1). Each study consisted of an equilibration, a basal, and three 90-min test periods (P1, P2, and P3) during which somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and peripheral glucose were infused. Saline was infused intraportally in P1. During P2 and P3, GLP-1 was infused intraportally at 0.9 and 5.1 pmol · kg−1 · min−1in eight dogs, at 10 and 20 pmol · kg−1 · min−1in seven dogs, and at 0 pmol · kg−1 · min−1in eight dogs (control group). Net hepatic glucose uptake was significantly enhanced during GLP-1 infusion at 20 pmol · kg−1 · min−1[21.8 vs. 13.4 μmol · kg−1 · min−1(control), P < 0.05]. Glucose utilization was significantly increased during infusion at 10 and 20 pmol · kg−1 · min−1[87.3 ± 8.3 and 105.3 ± 12.8, respectively, vs. 62.2 ± 5.3 and 74.7 ± 7.4 μmol · kg−1 · min−1(control), P < 0.05]. The glucose infusion rate required to maintain hyperglycemia was increased ( P < 0.05) during infusion of GLP-1 at 5.1, 10, and 20 pmol · kg−1 · min−1(22, 36, and 32%, respectively, greater than control). Nonhepatic glucose uptake increased significantly during delivery of GLP-1 at 5.1 and 10 pmol · kg−1 · min−1(25 and 46% greater than control) and tended ( P = 0.1) to increase during GLP-1 infusion at 20 pmol · kg−1 · min−1(24% greater than control). Intraportal infusion of GLP-1 at high physiological and pharmacological rates increased glucose disposal primarily in nonhepatic tissues.

Vagal cooling and concomitant portal norepinephrine infusion do not reduce net hepatic glucose uptake in conscious dogs

2004 ◽  
Vol 287 (4) ◽  
pp. R742-R748 ◽  
Author(s):  
Sylvain Cardin ◽  
Michael J. Pagliassotti ◽  
Mary Courtney Moore ◽  
Dale S. Edgerton ◽  
Margaret Lautz ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Conscious Dogs ◽  
Vagus Nerves ◽  
Period 2 ◽  
Hepatic Glucose ◽  
Group 2 ◽  
Infusion Of Norepinephrine ◽  
Hepatic Glucose Uptake ◽  
Intraportal Infusion ◽  
Group 1

We examined the role of efferent neural signaling in regulation of net hepatic glucose uptake (NHGU) in two groups of conscious dogs with hollow perfusable coils around their vagus nerves, using tracer and arteriovenous difference techniques. Somatostatin, intraportal insulin and glucagon at fourfold basal and basal rates, and intraportal glucose at 3.8 mg·kg−1·min−1 were infused continuously. From 0 to 90 min [ period 1 ( P1)], the coils were perfused with a 37°C solution. During period 2 [ P2; 90–150 min in group 1 ( n = 3); 90–180 min in group 2 ( n = 6)], the coils were perfused with −15°C solution to eliminate vagal signaling, and the coils were subsequently perfused with 37°C solution during period 3 ( P3). In addition, group 2 received an intraportal infusion of norepinephrine at 16 ng·kg−1·min−1 during P2. The effectiveness of vagal suppression was demonstrated by the increase in heart rate during P2 (111 ± 17, 167 ± 16, and 105 ± 13 beats/min in group 1 and 71 ± 6, 200 ± 11, and 76 ± 6 beats/min in group 2 during P1–P3, respectively) and by prolapse of the third eyelid during P2. Arterial plasma glucose, insulin, and glucagon concentrations; hepatic blood flow; and hepatic glucose load did not change significantly during P1–P3. NHGU during P1-P3 was 2.7 ± 0.4, 4.1 ± 0.6, and 4.0 ± 1.2 mg·kg−1·min−1 in group 1 and 5.0 ± 0.9, 5.6 ± 0.7, and 6.1 ± 0.9 mg·kg−1·min−1 in group 2 (not significant among periods). Interruption of vagal signaling with or without intraportal infusion of norepinephrine to augment sympathetic tone did not suppress NHGU during portal glucose delivery, suggesting the portal signal stimulates NHGU independently of vagal efferent flow.

Intraportal administration of neuropeptide Y and hepatic glucose metabolism

2008 ◽  
Vol 294 (4) ◽  
pp. R1197-R1204 ◽  
Author(s):  
Makoto Nishizawa ◽  
Masakazu Shiota ◽  
Mary Courtney Moore ◽  
Stephanie M. Gustavson ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Neuropeptide Y ◽  
Glucose Uptake ◽  
Infusion Rate ◽  
Whole Body ◽  
Glucose Disposal ◽  
Control Group ◽  
Intravenous Glucose ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake

We examined whether intraportal delivery of neuropeptide Y (NPY) affects glucose metabolism in 42-h-fasted conscious dogs using arteriovenous difference methodology. The experimental period was divided into three subperiods (P1, P2, and P3). During all subperiods, the dogs received infusions of somatostatin, intraportal insulin (threefold basal), intraportal glucagon (basal), and peripheral intravenous glucose to increase the hepatic glucose load twofold basal. Following P1, in the NPY group ( n = 7), NPY was infused intraportally at 0.2 and 5.1 pmol·kg−1·min−1 during P2 and P3, respectively. The control group ( n = 7) received intraportal saline infusion without NPY. There were no significant changes in hepatic blood flow in NPY vs. control. The lower infusion rate of NPY (P2) did not enhance net hepatic glucose uptake. During P3, the increment in net hepatic glucose uptake (compared with P1) was 4 ± 1 and 10 ± 2 μmol·kg−1·min−1 in control and NPY, respectively ( P < 0.05). The increment in net hepatic fractional glucose extraction during P3 was 0.015 ± 0.005 and 0.039 ± 0.008 in control and NPY, respectively ( P < 0.05). Net hepatic carbon retention was enhanced in NPY vs. control (22 ± 2 vs. 14 ± 2 μmol·kg−1·min−1, P < 0.05). There were no significant differences between groups in the total glucose infusion rate. Thus, intraportal NPY stimulates net hepatic glucose uptake without significantly altering whole body glucose disposal in dogs.

Inclusion of low amounts of fructose with an intraportal glucose load increases net hepatic glucose uptake in the presence of relative insulin deficiency in dog

2005 ◽  
Vol 288 (6) ◽  
pp. E1160-E1167 ◽  
Author(s):  
Masakazu Shiota ◽  
Pietro Galassetti ◽  
Kayano Igawa ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Blood Glucose ◽  
Glucose Uptake ◽  
Control Period ◽  
Glucose Infusion ◽  
Control Group ◽  
Hepatic Glycogen ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Arterial Blood Glucose ◽  
Hepatic Glucose Uptake

The effect of small amounts of fructose on net hepatic glucose uptake (NHGU) during hyperglycemia was examined in the presence of insulinopenia in conscious 42-h fasted dogs. During the study, somatostatin (0.8 μg·kg−1·min−1) was given along with basal insulin (1.8 pmol·kg−1·min−1) and glucagon (0.5 ng·kg−1·min−1). After a control period, glucose (36.1 μmol·kg−1·min−1) was continuously given intraportally for 4 h with (2.2 μmol·kg−1·min−1) or without fructose. In the fructose group, the sinusoidal blood fructose level (nmol/ml) rose from <16 to 176 ± 11. The infusion of glucose alone (the control group) elevated arterial blood glucose (μmol/ml) from 4.3 ± 0.3 to 11.2 ± 0.6 during the first 2 h after which it remained at 11.6 ± 0.8. In the presence of fructose, glucose infusion elevated arterial blood glucose (μmol/ml) from 4.3 ± 0.2 to 7.4 ± 0.6 during the first 1 h after which it decreased to 6.1 ± 0.4 by 180 min. With glucose infusion, net hepatic glucose balance (μmol·kg−1·min−1) switched from output (8.9 ± 1.7 and 13.3 ± 2.8) to uptake (12.2 ± 4.4 and 29.4 ± 6.7) in the control and fructose groups, respectively. Average NHGU (μmol·kg−1·min−1) and fractional glucose extraction (%) during last 3 h of the test period were higher in the fructose group (30.6 ± 3.3 and 14.5 ± 1.4) than in the control group (15.0 ± 4.4 and 5.9 ± 1.8). Glucose 6-phosphate and glycogen content (μmol glucose/g) in the liver and glucose incorporation into hepatic glycogen (μmol glucose/g) were higher in the fructose (218 ± 2, 283 ± 25, and 109 ± 26, respectively) than in the control group (80 ± 8, 220 ± 31, and 41 ± 5, respectively). In conclusion, small amounts of fructose can markedly reduce hyperglycemia during intraportal glucose infusion by increasing NHGU even when insulin secretion is compromised.

Interaction Between Insulin and Glucose-Delivery Route in Regulation of Net Hepatic Glucose Uptake in Conscious Dogs

Diabetes ◽  
1990 ◽  
Vol 39 (1) ◽  
pp. 87-95 ◽  
Author(s):  
B. A. Adkins-Marshall ◽  
S. R. Myers ◽  
G. K. Hendrick ◽  
P. E. Williams ◽  
K. Triebwasser ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Conscious Dogs ◽  
Hepatic Glucose ◽  
Delivery Route ◽  
Hepatic Glucose Uptake

Hepatic glucose uptake rapidly decreases after removal of the portal signal in conscious dogs

1998 ◽  
Vol 275 (6) ◽  
pp. E987-E992 ◽  
Author(s):  
Po-Shiuan Hsieh ◽  
Mary Courtney Moore ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Glucose Uptake ◽  
Experimental Period ◽  
Glucose Infusion ◽  
Conscious Dogs ◽  
Glucose Load ◽  
Peripheral Vein ◽  
Peripheral Tissues ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Arterial Insulin

The aim of this study was to assess the decay of the effect of the portal signal on net hepatic glucose uptake (NHGU). Experiments were performed on five 42-h-fasted conscious dogs. After the 40-min basal period, somatostatin was given peripherally along with insulin (1.8 pmol ⋅ kg−1 ⋅ min−1) and glucagon (0.65 ng ⋅ kg−1 ⋅ min−1) intraportally. In the first experimental period (Pe-GLU-1; 90 min), glucose was infused into a peripheral vein to double the glucose load to the liver (HGL). In the second experimental period (Po-GLU; 90 min), glucose (20.1 μmol ⋅ kg−1 ⋅ min−1) was infused intraportally and the peripheral glucose infusion was reduced to maintain the same HGL. In the third period (Pe-GLU-2; 120 min), the portal glucose infusion was stopped and the peripheral glucose infusion was increased to again sustain HGL. Arterial insulin levels (42 ± 3, 47 ± 3, 43 ± 3 pmol/l) were basal and similar in the Pe-GLU-1, Po-GLU, and Pe-GLU-2 periods, respectively. Arterial glucagon levels were also basal and similar (51 ± 3, 49 ± 2, 46 ± 2 ng/l) in the three experimental periods. The glucose loads to the liver were 251 ± 11, 274 ± 14, and 276 ± 12 μmol ⋅ kg−1 ⋅ min−1, respectively. NHGU was 6.3 ± 2.4, 19.1 ± 2.8, and 9.2 ± 1.2 μmol ⋅ kg−1 ⋅ min−1, and nonhepatic glucose uptake (non-HGU) was 23.6 ± 3.0, 5.3 ± 1.8, and 25.5 ± 3.7 μmol ⋅ kg−1 ⋅ min−1in the three periods, respectively. Cessation of the portal signal for only 10 min shifted NHGU and non-HGU to 9.4 ± 2.2 and 25.0 ± 2.8 μmol ⋅ kg−1 ⋅ min−1, respectively; thus the effect of the portal signal was rapidly reversed both at the liver and peripheral tissues.

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