Combined intraportal infusion of acetylcholine and adrenergic blockers augments net hepatic glucose uptake

2000 ◽  
Vol 278 (3) ◽  
pp. E544-E552 ◽  
Author(s):  
Masakazu Shiota ◽  
Patricia Jackson ◽  
Pietro Galassetti ◽  
Melanie Scott ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Nervous Activity ◽  
Adrenergic Blockade ◽  
Test Protocol ◽  
Control Protocol ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Adrenergic Blockers ◽  
Hepatic Glucose Uptake

Portal glucose delivery in the conscious dog augments net hepatic glucose uptake (NHGU). To investigate the possible role of altered autonomic nervous activity in the effect of portal glucose delivery, the effects of adrenergic blockade and acetylcholine (ACh) on hepatic glucose metabolism were examined in 42-h-fasted conscious dogs. Each study consisted of an equilibration (−120 to −20 min), a control (−20 to 0 min), and a hyperglycemic-hyperinsulinemic period (0 to 300 min). During the last period, somatostatin (0.8 μg ⋅ kg−1⋅ min−1) was infused along with intraportal insulin (1.2 mU ⋅ kg−1⋅ min−1) and glucagon (0.5 ng ⋅ kg−1⋅ min−1). Hepatic sinusoidal insulin was four times basal (73 ± 7 μU/ml) and glucagon was basal (55 ± 7 pg/ml). Glucose was infused peripherally (0–300 min) to create hyperglycemia (220 mg/dl). In test protocol, phentolamine and propranolol were infused intraportally at 0.2 μg and 0.1 μg ⋅ kg−1⋅ min−1from 120 min on. ACh was infused intraportally at 3 μg ⋅ kg−1⋅ min−1from 210 min on. In control protocol, saline was given in place of the blockers and ACh. Hyperglycemia-hyperinsulinemia switched the net hepatic glucose balance (mg ⋅ kg−1⋅ min−1) from output (2.1 ± 0.3 and 1.1 ± 0.2) to uptake (2.8 ± 0.9 and 2.6 ± 0.6) and lactate balance (μmol ⋅ kg−1⋅ min−1) from uptake (7.5 ± 2.2 and 6.7 ± 1.6) to output (3.7 ± 2.6 and 3.9 ± 1.6) by 120 min in the control and test protocols, respectively. Therefter, in the control protocol, NHGU tended to increase slightly (3.0 ± 0.6 mg ⋅ kg−1⋅ min−1by 300 min). In the test protocol, adrenergic blockade did not alter NHGU, but ACh infusion increased it to 4.4 ± 0.6 and 4.6 ± 0.6 mg ⋅ kg−1⋅ min−1by 220 and 300 min, respectively. These data are consistent with the hypothesis that alterations in nerve activity contribute to the increase in NHGU seen after portal glucose delivery.

Intrahepatic glucose: a requirement for neonatal ODC induction by specific hormones

1984 ◽  
Vol 247 (2) ◽  
pp. E243-E250
Author(s):  
G. Evoniuk ◽  
C. Kuhn ◽  
S. Schanberg
Keyword(s):  
Glucose Uptake ◽  
Intragastric Administration ◽  
Nutritional Deprivation ◽  
Rat Pups ◽  
Absolute Requirement ◽  
Whole Milk ◽  
Hepatic Glucose ◽  
Nutrient Administration ◽  
Hepatic Glucose Uptake

We have shown previously that short-term nutritional deprivation causes a tissue-specific loss of liver ornithine decarboxylase (ODC) induction after isoproterenol, phenylephrine, or glucagon administration in rat pups. To examine the role of nutrition in the regulation of hepatic ODC, we tested the ability of intragastric nutrient administration to reverse nutritionally related deficits in the ODC response to hormonal challenge. Intragastric whole milk was effective in restoring ODC induction and accumulation of its immediate product, putrescine, in response to isoproterenol administration. Glucose was shown to mediate this effect by the ability of intragastric skimmed milk, lactose, galactose, or D-glucose to return ODC induction, and the inability of casein, sucrose, fructose, L-glucose, or pyruvate plus lactate to do so. D-Glucose also reestablished ODC induction by phenylephrine and glucagon. Parenteral administration of D-glucose produced results comparable to those obtained after intragastric administration. Isoproterenol induction of ODC was prevented when hepatic glucose uptake was blocked by phlorizin but not by blockade of central nervous system glucose uptake with 2-deoxyglucose. We conclude that intrahepatic glucose is an absolute requirement for hepatic ODC induction by isoproterenol, phenylephrine, or glucagon in preweanling rats.

Hepatic glucose metabolism during intraduodenal glucose infusion: impact of infection

2000 ◽  
Vol 279 (1) ◽  
pp. E108-E115
Author(s):  
Owen P. McGuinness ◽  
Joseph Ejiofor ◽  
D. Brooks Lacy ◽  
Nancy Schrom
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Fibrin Clot ◽  
Glucose Absorption ◽  
Glucose Infusion ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Glycogen Deposition ◽  
Hepatic Glucose Uptake

We previously reported that infection decreases hepatic glucose uptake when glucose is given as a constant peripheral glucose infusion (8 mg · kg−1· min−1). This impairment persisted despite greater hyperinsulinemia in the infected group. In a normal setting, hepatic glucose uptake can be further enhanced if glucose is given gastrointestinally. Thus the aim of this study was to determine whether hepatic glucose uptake is impaired during an infection when glucose is given gastrointestinally. Thirty-six hours before study, a sham (SH, n = 7) or Escherichia coli-containing (2 × 109organisms/kg; INF; n = 7) fibrin clot was placed in the peritoneal cavity of chronically catheterized dogs. After the 36 h, a glucose bolus (150 mg/kg) followed by a continuous infusion (8 mg · kg−1· min−1) of glucose was given intraduodenally to conscious dogs for 240 min. Tracer ([3-3H]glucose and [U-14C]glucose) and arterial-venous difference techniques were used to assess hepatic and intestinal glucose metabolism. Infection increased hepatic blood flow (35 ± 5 vs. 47 ± 3 ml · kg−1· min−1; SH vs. INF) and basal glucose rate of appearance (2.1 ± 0.2 vs. 3.3 ± 0.1 mg · kg−1· min−1). Arterial insulin concentrations increased similarly in SH and INF during the last hour of glucose infusion (38 ± 8 vs. 46 ± 20 μU/ml), and arterial glucagon concentrations fell (62 ± 14 to 30 ± 3 vs. 624 ± 191 to 208 ± 97 pg/ml). Net intestinal glucose absorption was decreased in INF, attenuating the increase in blood glucose caused by the glucose load. Despite this, net hepatic glucose uptake (1.6 ± 0.8 vs. 2.4 ± 0.9 mg · kg−1· min−1; SH vs. INF) and consequently tracer-determined glycogen synthesis (1.3 ± 0.3 vs. 1.0 ± 0.3 mg · kg−1· min−1) were similar between groups. In summary, infection impairs net glucose absorption, but not net hepatic glucose uptake or glycogen deposition, when glucose is given intraduodenally.

Fructose augments infection-impaired net hepatic glucose uptake during TPN administration

2001 ◽  
Vol 280 (5) ◽  
pp. E703-E711 ◽  
Author(s):  
Christine M. Donmoyer ◽  
Joseph Ejiofor ◽  
D. Brooks Lacy ◽  
Sheng-Song Chen ◽  
Owen P. McGuinness
Keyword(s):  
Glucose Uptake ◽  
Vena Cava ◽  
Fibrin Clot ◽  
Glycogen Storage ◽  
Glucose Disposal ◽  
Lactate Release ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Arteriovenous Difference

During chronic total parenteral nutrition (TPN), net hepatic glucose uptake (NHGU) and net hepatic lactate release (NHLR) are markedly reduced (↓∼45 and ∼65%, respectively) with infection. Because small quantities of fructose are known to augment hepatic glucose uptake and lactate release in normal fasted animals, the aim of this work was to determine whether acute fructose infusion with TPN could correct the impairments in NHGU and NHLR during infection. Chronically catheterized conscious dogs received TPN for 5 days via the inferior vena cava at a rate designed to match daily basal energy requirements. On the third day of TPN administration, a sterile (SHAM, n = 12) or Escherichia coli-containing (INF, n = 11) fibrin clot was implanted in the peritoneal cavity. Forty-two hours later, somatostatin was infused with intraportal replacement of insulin (12 ± 2 vs. 24 ± 2 μU/ml, SHAM vs. INF, respectively) and glucagon (24 ± 4 vs. 92 ± 5 pg/ml) to match concentrations previously observed in sham and infected animals. After a 120-min basal period, animals received either saline (Sham+S, n = 6; Inf+S, n = 6) or intraportal fructose (0.7 mg · kg−1· min−1; Sham+F, n = 6; Inf+F, n = 5) infusion for 180 min. Isoglycemia of 120 mg/dl was maintained with a variable glucose infusion. Combined tracer and arteriovenous difference techniques were used to assess hepatic glucose metabolism. Acute fructose infusion with TPN augmented NHGU by 2.9 ± 0.4 and 2.5 ± 0.3 mg · kg−1· min−1in Sham+F and Inf+F, respectively. The majority of liver glucose uptake was stored as glycogen, and NHLR did not increase substantially. Therefore, despite an infection-induced impairment in NHGU and different hormonal environments, small amounts of fructose enhanced NHGU similarly in sham and infected animals. Glycogen storage, not lactate release, was the preferential fate of the fructose-induced increase in hepatic glucose disposal in animals adapted to TPN.

scholarly journals Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal

2006 ◽  
Vol 290 (1) ◽  
pp. E9-E16 ◽  
Author(s):  
Catherine A. DiCostanzo ◽  
Dominique P. Dardevet ◽  
Doss W. Neal ◽  
Margaret Lautz ◽  
Eric Allen ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Sympathetic Nerves ◽  
Glucose Infusion ◽  
Sympathetic Denervation ◽  
Hepatic Glucose ◽  
The Common ◽  
Hepatic Glucose Uptake ◽  
Arteriovenous Difference ◽  
Infusion Period

Portal glucose delivery enhances net hepatic glucose uptake (NHGU) relative to peripheral glucose delivery. We hypothesize that the sympathetic nervous system normally restrains NHGU, and portal glucose delivery relieves the inhibition. Two groups of 42-h-fasted conscious dogs were studied using arteriovenous difference techniques. Denervated dogs (DEN; n = 10) underwent selective sympathetic denervation by cutting the nerves at the celiac nerve bundle near the common hepatic artery; control dogs (CON; n = 10) underwent a sham procedure. After a 140-min basal period, somatostatin was given along with basal intraportal infusions of insulin and glucagon. Glucose was infused peripherally to double the hepatic glucose load (HGL) for 90 min ( P1). In P2, glucose was infused intraportally (3–4 mg·kg−1·min−1), and the peripheral glucose infusion was reduced to maintain the HGL for 90 min. This was followed by 90 min ( P3) in which portal glucose infusion was terminated and peripheral glucose infusion was increased to maintain the HGL. P1 and P3 were averaged as the peripheral glucose infusion period (PE). The average HGLs (mg·kg−1·min−1) in CON and DEN were 55 ± 3 and 54 ± 4 in the peripheral periods and 55 ± 3 and 55 ± 4 in P2, respectively. The arterial insulin and glucagon levels remained basal in both groups. NHGU (mg·kg−1·min−1) in CON averaged 1.7 ± 0.3 during PE and increased to 2.9 ± 0.3 during P2. NHGU (mg·kg−1·min−1) was greater in DEN than CON ( P < 0.05) during PE (2.9 ± 0.4) and failed to increase significantly (3.2 ± 0.2) during P2 (not significant vs. CON). Selective sympathetic denervation increased NHGU during hyperglycemia but significantly blunted the response to portal glucose delivery.

scholarly journals Chronic overeating impairs hepatic glucose uptake and disposition

2015 ◽  
Vol 308 (10) ◽  
pp. E860-E867 ◽  
Author(s):  
Katie C. Coate ◽  
Guillaume Kraft ◽  
Masakazu Shiota ◽  
Marta S. Smith ◽  
Ben Farmer ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Hepatic Glucose Metabolism ◽  
Significant Difference ◽  
Hepatic Glucose ◽  
Glycogen Deposition ◽  
Hepatic Glucose Uptake ◽  
Glycogen Phosphorylase Activity

Dogs consuming a hypercaloric high-fat and -fructose diet (52 and 17% of total energy, respectively) or a diet high in either fructose or fat for 4 wk exhibited blunted net hepatic glucose uptake (NHGU) and glycogen deposition in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery. The effect of a hypercaloric diet containing neither fructose nor excessive fat has not been examined. Dogs with an initial weight of ≈25 kg consumed a chow and meat diet (31% protein, 44% carbohydrate, and 26% fat) in weight-maintaining (CTR; n = 6) or excessive (Hkcal; n = 7) amounts for 4 wk (cumulative weight gain 0.0 ± 0.3 and 1.5 ± 0.5 kg, respectively, P < 0.05). They then underwent clamp studies with infusions of somatostatin and intraportal insulin (4× basal) and glucagon (basal). The hepatic glucose load was doubled with peripheral (Pe) glucose infusion for 90 min (P1) and intraportal glucose at 4 mg·kg−1·min−1 plus Pe glucose for the final 90 min (P2). NHGU was blunted ( P < 0.05) in Hkcal during both periods (mg·kg−1·min−1; P1: 1.7 ± 0.2 vs. 0.3 ± 0.4; P2: 3.6 ± 0.3 vs. 2.3 ± 0.4, CTR vs. Hkcal, respectively). Terminal hepatic glucokinase catalytic activity was reduced nearly 50% in Hkcal vs. CTR ( P < 0.05), although glucokinase protein did not differ between groups. In Hkcal vs. CTR, liver glycogen was reduced 27% ( P < 0.05), with a 91% increase in glycogen phosphorylase activity ( P < 0.05) but no significant difference in glycogen synthase activity. Thus, Hkcal impaired NHGU and glycogen synthesis compared with CTR, indicating that excessive energy intake, even if the diet is balanced and nutritious, negatively impacts hepatic glucose metabolism.

Impact of continuous and pulsatile insulin delivery on net hepatic glucose uptake

2005 ◽  
Vol 289 (2) ◽  
pp. E232-E240 ◽  
Author(s):  
Jaime M. Grubert ◽  
Margaret Lautz ◽  
D. Brooks Lacy ◽  
Mary C. Moore ◽  
Ben Farmer ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Hepatic Metabolism ◽  
Insulin Delivery ◽  
Experimental Period ◽  
Constant Infusion ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Arterial Plasma ◽  
Hepatic Glucose Uptake

The pancreas releases insulin in a pulsatile manner; however, studies assessing the liver’s response to insulin have used constant infusion rates. Our aims were to determine whether the secretion pattern of insulin [continuous (CON) vs. pulsatile] in the presence of hyperglycemia 1) influences net hepatic glucose uptake (NHGU) and 2) entrains NHGU. Chronically catheterized conscious dogs fasted for 42 h received infusions including peripheral somatostatin, portal insulin (0.25 mU·kg−1·min−1), peripheral glucagon (0.9 ng·kg−1·min−1), and peripheral glucose at a rate double the glucose load to the liver. After the basal period, insulin was infused for 210 min at either four times the basal rate (1 mU·kg−1·min−1) or an identical amount in pulses of 1 and 4 min duration, followed by intervals of 11 and 8 min (CON, 1/11, and 4/8, respectively) in which insulin was not infused. A variable peripheral glucose infusion containing [3H]glucose clamped glucose levels at twice the basal level (∼200 mg/dl) throughout each study. Hepatic metabolism was assessed by combining tracer and arteriovenous difference techniques. Arterial plasma insulin (μU/ml) either increased from basal levels of 6 ± 1 to a constant level of 22 ± 4 in CON or oscillated from 5 ± 1 to 416 ± 79 and from 6 ± 1 to 123 ± 43 in 1/11 and 4/8, respectively. NHGU (−0.8 ± 0.3, 0.4 ± 0.2, and −0.9 ± 0.4 mg·kg−1·min−1) and net hepatic fractional extraction of glucose (0.04 ± 0.01, 0.04 ± 0.01, and 0.05 ± 0.01 mg·kg−1·min−1) were similar during the experimental period. Spectral analysis was performed to assess whether a correlation existed between the insulin secretion pattern and NHGU. NHGU was not augmented by pulsatile insulin delivery, and there is no evidence of entrainment in hepatic glucose metabolism. Thus the loss of insulin pulsatility per se likely has little or no impact on the effectiveness of insulin in regulating liver glucose uptake.

Attenuation of glucose metabolic changes resulting from TNF-alpha administration by adrenergic blockade

1992 ◽  
Vol 262 (4) ◽  
pp. R628-R635 ◽  
Author(s):  
G. J. Bagby ◽  
C. H. Lang ◽  
N. Skrepnik ◽  
J. J. Spitzer
Keyword(s):  
Glucose Uptake ◽  
Glucose Production ◽  
Whole Body ◽  
Tnf Alpha ◽  
Adrenergic System ◽  
Adrenergic Blockade ◽  
Hepatic Glucose ◽  
Glucose Output

Administration of tumor necrosis factor (TNF-alpha) increases whole body glucose kinetics and stimulates in vivo glucose uptake by several tissues. Because circulating catecholamines are also increased after TNF-alpha administration, the present study was conducted to examine the potential role of the adrenergic system in eliciting these changes. Rats given 150 micrograms TNF-alpha/kg by intravenous infusion over a 30-min period exhibited an increased rate of glucose appearance (glucose Ra). Combined alpha- and beta-adrenergic blockade (phentolamine and propranolol infusion) prevented the TNF-alpha-induced increase in glucose Ra without influencing plasma glucagon or corticosterone levels. TNF-alpha infusion also increased in vivo glucose utilization (Rg), measured with 2-deoxy-[14C]glucose, in spleen (86%), liver (80%), skin (47%), ileum (71%), lung (53%), and heart (112%). Adrenergic blockade prevented the tissue Rg increase in the spleen, liver, and skin; partially reduced it in the ileum; but did not abrogate it in the lung or heart. The effect of blockade was primarily due to inhibition of the TNF-alpha-induced increase in hepatic glucose output. Whereas the adrenergic system plays a major role on the effect of TNF-alpha on whole body glucose production, its importance in directly mediating TNF-alpha's effect on tissue glucose uptake is minimal.

scholarly journals Quantitative Determination of Hepatic Glucose Uptake Using an Innovative Approach

1991 ◽  
Vol 37 (Supplement) ◽  
pp. S35-S42 ◽  
Author(s):  
Ryuzo KAWAMORI ◽  
Minoru KUBOTA ◽  
Masahiko IKEDA ◽  
Munehide MATSUHISA ◽  
Masashi KUBOTA ◽  
...  
Keyword(s):  
Quantitative Determination ◽  
Glucose Uptake ◽  
Innovative Approach ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake

scholarly journals Nonhepatic response to portal glucose delivery in conscious dogs

2000 ◽  
Vol 279 (6) ◽  
pp. E1271-E1277 ◽  
Author(s):  
Mary Courtney Moore ◽  
Po-Shiuan Hsieh ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Glucose Uptake ◽  
Glucose Infusion ◽  
Glucose Load ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
The Difference ◽  
Arterial Plasma ◽  
Arterial Blood Glucose ◽  
Blood Glucose Concentrations ◽  
Hepatic Glucose Uptake

The glycemic and hormonal responses and net hepatic and nonhepatic glucose uptakes were quantified in conscious 42-h-fasted dogs during a 180-min infusion of glucose at 10 mg · kg−1 · min−1 via a peripheral (Pe10, n = 5) or the portal (Po10, n = 6) vein. Arterial plasma insulin concentrations were not different during the glucose infusion in Pe10 and Po10 (37 ± 6 and 43 ± 12 μU/ml, respectively), and glucagon concentrations declined similarly throughout the two studies. Arterial blood glucose concentrations during glucose infusion were not different between groups (125 ± 13 and 120 ± 6 mg/dl in Pe10 and Po10, respectively). Portal glucose delivery made the hepatic glucose load significantly greater (36 ± 3 vs. 46 ± 5 mg · kg−1 · min−1 in Pe10 vs. Po10, respectively, P < 0.05). Net hepatic glucose uptake (NHGU; 1.1 ± 0.4 vs. 3.1 ± 0.4 mg · kg−1 · min−1) and fractional extraction (0.03 ± 0.01 vs. 0.07 ± 0.01) were smaller ( P < 0.05) in Pe10 than in Po10. Nonhepatic (primarily muscle) glucose uptake was correspondingly increased in Pe10 compared with Po10 (8.9 ± 0.4 vs. 6.9 ± 0.4 mg · kg−1 · min−1, P < 0.05). Approximately one-half of the difference in NHGU between groups could be accounted for by the difference in hepatic glucose load, with the remainder attributable to the effect of the portal signal itself. Even in the absence of somatostatin and fixed hormone concentrations, the portal signal acts to alter partitioning of a glucose load among the tissues, stimulating NHGU and reducing peripheral glucose uptake.

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