scholarly journals The disposition of carbohydrate between glycogenesis, lipogenesis and oxidation in liver during the starved-to-fed transition

1988 ◽  
Vol 252 (2) ◽  
pp. 325-330 ◽  
Author(s):  
M J Holness ◽  
P A MacLennan ◽  
T N Palmer ◽  
M C Sugden
Keyword(s):  
Glucose Uptake ◽  
Pyruvate Dehydrogenase ◽  
Temporal Relationship ◽  
Glycogen Synthesis ◽  
Glucose Flux ◽  
Hepatic Glucose ◽  
Ad Libitum ◽  
Time Courses

A comparison was made between the time courses of restoration of pyruvate dehydrogenase activities, fructose 2,6-bisphosphate concentrations and lipogenic rates, together with net hepatic glucose flux and glycogen synthesis/deposition in livers of 48 h-starved rats provided with laboratory chow ad libitum for up to 24 h. Increased glycogenesis, lipogenesis and net glucose uptake were observed after 1 h of re-feeding, preceding re-activation of pyruvate dehydrogenase, which occurred after 3-4 h. Increased concentrations of fructose 2,6-bisphosphate were only observed after 5-6 h. The implication of the temporal relationship between these parameters is discussed.

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.

Brief food restriction increases FA oxidation and glycogen synthesis under insulin-stimulated conditions

2002 ◽  
Vol 282 (4) ◽  
pp. R1210-R1218 ◽  
Author(s):  
Michelle Z. Tucker ◽  
Lorraine P. Turcotte
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Food Intake ◽  
Glucose Uptake ◽  
Food Restriction ◽  
Glycogen Synthesis ◽  
Palmitate Uptake ◽  
Ad Libitum ◽  
Muscle Triglyceride ◽  
White Gastrocnemius

To determine the effects of brief food restriction on fatty acid (FA) metabolism, hindlimbs of F344/BN rats fed either ad libitum (AL) or food restricted (FR) to 60% of baseline food intake for 28 days were perfused under hyperglycemic-hyperinsulinemic conditions (20 mM glucose, 1 mM palmitate, 1,000 μU/ml insulin, [3-3H]glucose, and [1-14C]palmitate). Basal glucose and insulin levels were significantly lower ( P < 0.05) in FR vs. AL rats. Palmitate uptake (34.3 ± 2.7 vs. 24.5 ± 3.1 nmol/g/min) and oxidation (3.8 ± 0.2 vs. 2.7 ± 0.3 nmol · g−1 · min−1) were significantly higher ( P < 0.05) in FR vs. AL rats, respectively. Glucose uptake was increased in FR rats and was accompanied by significant increases in red and white gastrocnemius glycogen synthesis, indicating an improvement in insulin sensitivity. Although muscle triglyceride (TG) levels were not significantly different between groups, glucose uptake and total preperfusion TG concentration were negatively correlated ( r 2 = 0.27, P < 0.05). In conclusion, our results show that under hyperglycemic-hyperinsulinemic conditions, brief FR resulted in an increase in FA oxidative disposal that may contribute to the improvement in insulin sensitivity.

Differential effect of amino acid infusion route on net hepatic glucose uptake in the dog

1999 ◽  
Vol 276 (2) ◽  
pp. E295-E302 ◽  
Author(s):  
Mary Courtney Moore ◽  
Po-Shiuan Hsieh ◽  
Paul J. Flakoll ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Amino Acid ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Portal Infusion

Concomitant portal infusion of gluconeogenic amino acids (GNGAA) and glucose significantly reduces net hepatic glucose uptake (NHGU), in comparison with NHGU during portal infusion of glucose alone. To determine whether this effect on NHGU is specific to the portal route of GNGAA delivery, somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and intraportal glucose (to increase the hepatic glucose load by ∼50%) were infused for 240 min. GNGAA were infused peripherally into a group of dogs (PeAA), at a rate to match the hepatic GNGAA load in a group of dogs that were given the same GNGAA mixture intraportally (PoAA) at 7.6 μmol ⋅ kg−1 ⋅ min−1(9). The arterial blood glucose concentrations and hepatic glucose loads were the same in the two groups, but NHGU (−0.9 ± 0.2 PoAA and −2.1 ± 0.5 mg ⋅ kg−1 ⋅ min−1in PeAA, P < 0.05) and net hepatic fractional extraction of glucose (2.6 ± 0.7% in PoAA vs. 5.9 ± 1.4% in PeAA, P < 0.05) differed. Neither the hepatic loads nor the net hepatic uptakes of GNGAA were significantly different in the two groups. Net hepatic glycogen synthesis was ∼2.5-fold greater in PeAA than PoAA ( P < 0.05). Intraportal, but not peripheral, amino acid infusion suppresses NHGU and net hepatic glycogen synthesis in response to intraportal glucose infusion.

scholarly journals A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin

2009 ◽  
Vol 297 (2) ◽  
pp. E358-E366 ◽  
Author(s):  
Jason J. Winnick ◽  
Zhibo An ◽  
Mary Courtney Moore ◽  
Christopher J. Ramnanan ◽  
Ben Farmer ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Control Period ◽  
In Vivo Studies ◽  
Hepatic Glycogen ◽  
Glycogen Level ◽  
Hepatic Glucose ◽  
Glycogen Deposition ◽  
Hepatic Glucose Uptake

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 1.18 ± 0.27 and 5.55 ± 0.53 mg·kg−1·min−1 and glycogen synthesis averaged 0.72 ± 0.24 and 3.98 ± 0.57 mg·kg−1·min−1 in the saline and fructose groups, respectively ( P < 0.05). During the 2-h hyperinsulinemic period, NHGU rose from 1.5 ± 0.4 and 0.9 ± 0.2 to 3.1 ± 0.6 and 2.5 ± 0.5 mg·kg−1·min−1 in the saline and fructose groups, respectively, a change of 1.6 mg·kg−1·min−1 in both groups despite a significantly greater liver glycogen level in the fructose-infused group. Likewise, the metabolic fate of the extracted glucose (glycogen, lactate, or carbon dioxide) was not different between groups. These data indicate that an acute physiological increase in the hepatic glycogen content does not alter liver glucose uptake and storage under hyperglycemic/hyperinsulinemic conditions in the dog.

scholarly journals Glucose autoregulation is the dominant component of the hormone-independent counterregulatory response to hypoglycemia in the conscious dog

2017 ◽  
Vol 313 (3) ◽  
pp. E273-E283 ◽  
Author(s):  
Justin M. Gregory ◽  
Noelia Rivera ◽  
Guillaume Kraft ◽  
Jason J. Winnick ◽  
Ben Farmer ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Muscle Group ◽  
The Body ◽  
Hepatic Glycogen ◽  
Hepatic Glucose ◽  
Group 3 ◽  
Per Se ◽  
Group 2 ◽  
Group 1

The contribution of hormone-independent counterregulatory signals in defense of insulin-induced hypoglycemia was determined in adrenalectomized, overnight-fasted conscious dogs receiving hepatic portal vein insulin infusions at a rate 20-fold basal. Either euglycemia was maintained ( group 1) or hypoglycemia (≈45 mg/dl) was allowed to occur. There were three hypoglycemic groups: one in which hepatic autoregulation against hypoglycemia occurred in the absence of sympathetic nervous system input ( group 2), one in which autoregulation occurred in the presence of norepinephrine (NE) signaling to fat and muscle ( group 3), and one in which autoregulation occurred in the presence of NE signaling to fat, muscle, and liver ( group 4). Average net hepatic glucose balance (NHGB) during the last hour for groups 1–4 was −0.7 ± 0.1, 0.3 ± 0.1 ( P < 0.01 vs. group 1), 0.7 ± 0.1 ( P = 0.01 vs. group 2), and 0.8 ± 0.1 ( P = 0.7 vs. group 3) mg·kg−1·min−1, respectively. Hypoglycemia per se ( group 2) increased NHGB by causing an inhibition of net hepatic glycogen synthesis. NE signaling to fat and muscle ( group 3) increased NHGB further by mobilizing gluconeogenic precursors resulting in a rise in gluconeogenesis. Lowering glucose per se decreased nonhepatic glucose uptake by 8.9 mg·kg−1·min−1, and the addition of increased neural efferent signaling to muscle and fat blocked glucose uptake further by 3.2 mg·kg−1·min−1. The addition of increased neural efferent input to liver did not affect NHGB or nonhepatic glucose uptake significantly. In conclusion, even in the absence of increases in counterregulatory hormones, the body can defend itself against hypoglycemia using glucose autoregulation and increased neural efferent signaling, both of which stimulate hepatic glucose production and limit glucose utilization.

scholarly journals Chronic consumption of a high-fat/high-fructose diet renders the liver incapable of net hepatic glucose uptake

2010 ◽  
Vol 299 (6) ◽  
pp. E887-E898 ◽  
Author(s):  
Katie Colbert Coate ◽  
Melanie Scott ◽  
Ben Farmer ◽  
Mary Courtney Moore ◽  
Marta Smith ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Large Animal Model ◽  
Oral Glucose ◽  
Large Animal ◽  
High Fructose ◽  
Hepatic Glucose ◽  
Glucose Tolerance Tests ◽  
Hepatic Glucose Uptake ◽  
Average Glucose

The objective of this study was to assess the response of a large animal model to high dietary fat and fructose (HFFD). Three different metabolic assessments were performed during 13 wk of feeding an HFFD ( n = 10) or chow control (CTR, n = 4) diet: oral glucose tolerance tests (OGTTs; baseline, 4 and 8 wk), hyperinsulinemic-euglycemic clamps (HIEGs; baseline and 10 wk) and hyperinsulinemic-hyperglycemic clamps (HIHGs, 13 wk). The ΔAUC for glucose during the OGTTs more than doubled after 4 and 8 wk of HFFD feeding, and the average glucose infusion rate required to maintain euglycemia during the HIEG clamps decreased by ≈30% after 10 wk of HFFD feeding. These changes did not occur in the CTR group. The HIHG clamps included experimental periods 1 (P1, 0–90 min) and 2 (P2, 90–180 min). During P1, somatostatin, basal intraportal glucagon, 4 × basal intraportal insulin, and peripheral glucose (to double the hepatic glucose load) were infused; during P2, glucose was also infused intraportally (4.0 mg·kg−1·min−1). Net hepatic glucose uptake during P1 and P2 was −0.4 ± 0.1 [output] and 0.2 ± 0.8 mg·kg−1·min−1 in the HFFD group, respectively, and 1.8 ± 0.8 and 3.5 ± 1.0 mg·kg−1·min−1 in the CTR group, respectively ( P < 0.05 vs. HFFD during P1 and P2). Glycogen synthesis through the direct pathway was 0.5 ± 0.2 and 1.5 ± 0.4 mg·kg−1·min−1 in the HFFD and CTR groups, respectively ( P < 0.05 vs. HFFD). In conclusion, chronic consumption of an HFFD diminished the sensitivity of the liver to hormonal and glycemic cues and resulted in a marked impairment in NHGU and glycogen synthesis.

scholarly journals Pregnancy augments hepatic glucose storage in response to a mixed meal

2011 ◽  
Vol 107 (4) ◽  
pp. 493-503 ◽  
Author(s):  
Mary Courtney Moore ◽  
Marta S. Smith ◽  
Cynthia C. Connolly
Keyword(s):  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
Area Under The Curve ◽  
Late Pregnancy ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Mixed Meal ◽  
Tracer Techniques ◽  
Hepatic Glucose

Studies were carried out on conscious female non-pregnant (NP) and pregnant (P; third-trimester) dogs (n 16; eight animals per group) to define the role of the liver in mixed meal disposition with arteriovenous difference and tracer techniques. Hepatic and hindlimb substrate disposal was assessed for 390 min during and after an intragastric mixed meal infusion labelled with [14C]glucose. The P dogs exhibited postprandial hyperglycaemia compared with NP dogs (area under the curve (AUC; change from basal over 390 min) of arterial plasma glucose: 86 680 (sem 12 140) and 187 990 (sem 33 990) mg/l in NP and P dogs, respectively; P < 0·05). Plasma insulin concentrations did not differ significantly between the groups (AUC: 88 230 (sem 16 314) and 69 750 (sem 19 512) pmol/l in NP and P dogs, respectively). Net hepatic glucose uptake totalled 3691 (sem 508) v. 5081 (sem 1145) mg/100 g liver in NP and P dogs, respectively (P = 0·38). The AUC of glucose oxidation by the gut and hindlimb were not different in NP and P dogs, but hepatic glucose oxidation (84 (sem 13) v. 206 (sem 30) mg/100 g liver) and glycogen synthesis (0·4 (sem 0·5) v. 26 (sem 0·7) g/100 g liver) were greater in P dogs (P < 0·05). The proportion of hepatic glycogen deposited via the direct pathway did not differ between the groups. Hindlimb glucose uptake and skeletal muscle glycogen synthesis was similar between the groups, although final glycogen concentrations were higher in NP dogs (9·6 (sem 0·6) v. 70 (sem 0·6) mg/g muscle; P < 0·05). Thus, hepatic glucose oxidation and glycogen storage were augmented in late pregnancy. Enhanced hepatic glycogen storage following a meal probably facilitates the maintenance of an adequate glucose supply to maternal and fetal tissues during the post-absorptive period.

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.

scholarly journals Acute activation of pyruvate dehydrogenase increases glucose oxidation in muscle without changing glucose uptake

2018 ◽  
Vol 315 (2) ◽  
pp. E258-E266 ◽  
Author(s):  
Lewin Small ◽  
Amanda E. Brandon ◽  
Lake-Ee Quek ◽  
James R. Krycer ◽  
David E. James ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Pyruvate Dehydrogenase ◽  
Glucose Oxidation ◽  
Kinase Inhibitor ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Acetyl Coa ◽  
Insulin Resistant

Pyruvate dehydrogenase (PDH) activity is a key component of the glucose/fatty acid cycle hypothesis for the regulation of glucose uptake and metabolism. We have investigated whether acute activation of PDH in muscle can alleviate the insulin resistance caused by feeding animals a high-fat diet (HFD). The importance of PDH activity in muscle glucose disposal under insulin-stimulated conditions was determined by infusing the PDH kinase inhibitor dichloroacetate (DCA) into HFD-fed Wistar rats during a hyperinsulinemic-euglycemic clamp. Acute DCA infusion did not alter glucose infusion rate, glucose disappearance, or hepatic glucose production but did decrease plasma lactate levels. DCA substantially increased muscle PDH activity; however, this did not improve insulin-stimulated glucose uptake in insulin-resistant muscle of HFD rats. DCA infusion increased the flux of pyruvate to acetyl-CoA and reduced glucose incorporation into glycogen and alanine in muscle. Similarly, in isolated muscle, DCA treatment increased glucose oxidation and decreased glycogen synthesis without changing glucose uptake. These results suggest that, although PDH activity controls the conversion of pyruvate to acetyl-CoA for oxidation, this has little effect on glucose uptake into muscle under insulin-stimulated conditions.

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