Hepatic glucose disposition during concomitant portal glucose and amino acid infusions in the dog (original) (raw)
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The American journal of clinical nutrition, 2008
Hepatic glucose uptake is enhanced by the portal delivery of glucose, which creates a negative arterioportal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven. We aimed to assess hepatic AA balance and protein synthesis with or without a negative arterioportal AA gradient. Somatostatin was infused intravenously, and insulin and glucagon were replaced intraportally at 4- and 3-fold basal rates, respectively, in 3 groups (n = 9 each) of conscious dogs with catheters for hepatic balance measurement. Arterial glucose concentrations were clamped at 9 mmol/L. An AA mixture was infused intravenously to maintain basal concentrations (EuAA), intraportally to mimic the postmeal AA increase (PoAA), or intravenously (PeAA) to match the hepatic AA load in PoAA. Protein synthesis was assessed with a primed, continuous [(14)C]leucine infusion. Net hepatic glucose uptake in the PoAA condition was < or =50% of that in the...
The American journal …, 2008
BackgroundHepatic glucose uptake is enhanced by portal delivery of glucose which creates a negative arterio-portal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven.ObjectiveWe aimed to assess hepatic AA balance and protein synthesis with or without a negative arterio-portal AA gradient.DesignSomatostatin was infused IV, and insulin and glucagon were replaced intraportally at 4- and 3-fold basal rates, respectively, in 3 groups (n=9 each) of conscious dogs with catheters for hepatic balance measurement. Arterial glucose concentrations were clamped at 9 mM. An AA mixture was infused IV to maintain basal concentrations (EuAA), intraportally to mimic the post-meal AA increase (PoAA), or IV (PeAA) to match the hepatic AA load in PoAA. Protein synthesis was assessed with a primed, continuous [14C]leucine infusion.ResultsNet hepatic glucose uptake in PoAA was ≤50% of that in EuAA and PeAA (P<0.05). The hepatic intracellular leucine concentration was 2- to 2.5-fold greater in PoAA and PeAA than EuAA (P<0.05); net hepatic leucine uptake and 14C leucine utilization were ≈2-fold greater (P<0.05) and albumin synthesis was 30% greater (P<0.05) in PoAA than EuAA and PeAA, Phosphorylation of ribosomal protein S6 (downstream of the mammalian target of Rapamycin complex 1 [mTORC1]) was significantly increased in PoAA, but not PeAA, vs EuAA.ConclusionsPortal, but not peripheral, AA delivery significantly enhanced hepatic protein synthesis under conditions where AA, glucose, insulin and glucagon did not differ at the liver, an effect apparently mediated by mTORC1 signalling.
Effects of continuous intramesenteric infusion of glucose and amino acids on food intake in rats
Physiology & Behavior, 1979
Prolonged infusions of various fluids at a rate of 21 ml/23.5 hr through the mesenteric vein and the vena cava were performed on rats and effects On ad lib food intake were determined. Results indicate that continuous intramesenteric infusion of 5-10% glucose solutions or a 5% Amimofusin L solution suppresses food intake. No effects were observed when solutions were infused via the caval vein. A 10% solution of 3-O-methyl-d-glucose did not affect food intake when introduced by either route. These data support directly the presence of glucose and amino acid receptive mechanisms in the portohepatic system involved in the control of food intake.
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
Direct and indirect effects of amino acids on hepatic glucose metabolism in humans
Diabetologia, 2003
Aim/hypothesis. The study was designed to examine the contribution of direct (substrate-mediated) and indirect (hormone-mediated) effects of amino acids on hepatic glucose metabolism in healthy men. Methods. The protocols were: (i) CON+S (n=7): control conditions with somatostatin to inhibit endogenous hormone release resulting in fasting plasma concentrations of amino acids, insulin (~28 pmol/l) and glucagon (~65 ng/l), (ii) AA+S (n=7): amino acid infusion-fasting insulinaemia-fasting glucagonaemia, (iii) GLUC+S (n=6): fasting amino acids-fasting insulinaemia-hyperglucagonaemia (~99 ng/l) and (iv) AA-S (n=5): amino acid infusion without somatostatin resulting in amino acid-induced hyperinsulinaemia (~61 pmol/l)-hyperglucagonaemia (~147 ng/l). Net glycogenolysis was calculated from liver glycogen concentrations using 13 C nuclear magnetic resonance spectroscopy. Total gluconeogenesis (GNG) was calculated by subtracting net glycogenolysis from endogenous glucose production (EGP) which was measured with [6,6-2 H 2 ]glucose. Net GNG was assessed with the 2 H 2 O method. Results. During AA+S and GLUC+S, plasma glucose increased by about 50% (p<0.01) due to a comparable rise in EGP. This was associated with a 53-% (p<0.05) and a 65% increase (p<0.01) of total and net GNG during AA+S, whereas net glycogenolysis rose by 70% (p<0.001) during GLUC+S. During AA-S, plasma glucose remained unchanged despite nearlydoubled (p<0.01) total GNG. Conclusion/interpretation. Conditions of postprandial amino acid elevation stimulate secretion of insulin and glucagon without affecting glycaemia despite markedly increased gluconeogenesis. Impaired insulin secretion unmasks the direct gluconeogenic effect of amino acids and increases plasma glucose. [Diabetologia (2003) 46:917-925]
Portal glucose delivery stimulates muscle but not liver protein metabolism
AJP: Endocrinology and Metabolism, 2012
Portal vein glucose delivery (the portal glucose signal) stimulates glucose uptake and glycogen storage by the liver, whereas portal amino acid (AA) delivery (the portal AA signal) induces an increase in protein synthesis by the liver. During a meal, both signals coexist and may interact. In this study, we compared the protein synthesis rates in the liver and muscle in response to portal or peripheral glucose infusion during intraportal infusion of a complete AA mixture. Dogs were surgically prepared with hepatic sampling catheters and flow probes. After a 42-h fast, they underwent a 3-h hyperinsulinemic (4× basal) hyperglucagonemic (3× basal) hyperglycemic (≈160 mg/dl) hyperaminoacidemic (hepatic load 1.5× basal; delivered intraportally) clamp (postprandial conditions). Glucose was infused either via a peripheral (PeG; n = 7) or the portal vein (PoG; n = 8). Protein synthesis was assessed with a primed, continuous [14C]leucine infusion. Net hepatic glucose uptake was stimulated by ...
AJP: Endocrinology and Metabolism, 2009
To determine the effect of an acute increase in hepatic glycogen on net hepatic glucose uptake (NHGU) and disposition in response to insulin in vivo, studies were performed on two groups of dogs fasted 18 h. During the first 4 h of the study, somatostatin was infused peripherally, while insulin and glucagon were replaced intraportally in basal amounts. Hyperglycemia was brought about by glucose infusion, and either saline ( n = 7) or fructose ( n = 7; to stimulate NHGU and glycogen deposition) was infused intraportally. A 2-h control period then followed, during which the portal fructose and saline infusions were stopped, allowing NHGU and glycogen deposition in the fructose-infused animals to return to rates similar to those of the animals that received the saline infusion. This was followed by a 2-h experimental period, during which hyperglycemia was continued but insulin infusion was increased fourfold in both groups. During the initial 4-h glycogen loading period, NHGU averaged ...
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.