Relationship of Hepatic Glucose Uptake to Intrahepatic Glucose Concentration in Fasted Rats After Glucose Load

Niewoehner, Catherine; Nuttall, Frank Q.

doi:10.2337/diab.37.11.1559

Cited by 41 publications

(28 citation statements)

References 41 publications

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“…GLUT2 expression is increased by high glucose concentrations (32). Because the presence of GLUT2 in the liver allows a rapid equilibration of the intracellular glucose level with the extracellular glucose level (33,34), net hepatic glucose flux represents a balance between glucokinase and glucose-6-phosphatase flux. Therefore it is likely that the excessive postprandial hyperglycemia evident in diabetic subjects is, in part, caused by a defect in net hepatic glucose uptake (NHGU) resulting from impaired glucose phosphorylation catalyzed by glucokinase and/or an increase in glucose dephosphorylation attributable to glucose-6-phosphatase.…”

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confidence: 99%

Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

et al. 2002

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Intraportal infusion of small amounts of fructose markedly augmented net hepatic glucose uptake (NHGU) during hyperglycemic hyperinsulinemia in conscious dogs. In this study, we examined whether the inclusion of catalytic amounts of fructose with a glucose load reduces postprandial hyperglycemia and the pancreatic ␤-cell response to a glucose load in conscious 42-hfasted dogs. Each study consisted of an equilibration (؊140 to ؊40 min), control (؊40 to 0 min), and test period (0 -240 min). During the latter period, glucose (44.4 mol ⅐ kg ؊1 ⅐ min ؊1 ) was continuously given intraduodenally with (2.22 mol ⅐ kg ؊1 ⅐ min ؊1 ) or without fructose. The glucose appearance rate in portal vein blood was not significantly different with or without the inclusion of fructose (41.3 ؎ 2.7 vs. 37.3 ؎ 8.3 mol ⅐ kg ؊1 ⅐ min ؊1 , respectively). In response to glucose infusion without the inclusion of fructose, the net hepatic glucose balance switched from output to uptake (from 10 ؎ 2 to 11 ؎ 4 mol ⅐ kg ؊1 ⅐ min ؊1 ) by 30 min and averaged 17 ؎ 6 mol ⅐ kg ؊1 ⅐ min ؊1 . The fractional extraction of glucose by the liver during the infusion period was 7 ؎ 2%. Net glycogen deposition was 2.44 mmol glucose equivalent/kg body wt; 49% of deposited glycogen was synthesized via the direct pathway. Net hepatic lactate production was 1.4 mmol/kg body wt. Arterial blood glucose rose from 4.1 ؎ 0.2 to 7.3 ؎ 0.4 mmol/l, and arterial plasma insulin rose from 42 ؎ 6 to 258 ؎ 66 pmol/l at 30 min, after which they decreased to 7.0 ؎ 0.5 mmol/l and 198 ؎ 66 pmol/l, respectively. Arterial plasma glucagon decreased from 54 ؎ 7 to 32 ؎ 3 ng/l. In response to intraduodenal glucose infusion in the presence of fructose, net hepatic glucose balance switched from 9 ؎ 1 mol ⅐ kg G lucose uptake by the liver contributes in a major way to the disposal of alimentary glucose (1). In healthy humans, 20 -30% of absorbed glucose is taken up by the liver, and hepatic glycogen synthesis accounts for the disposal of about 70% of that amount. Liver glycogen is synthesized by both direct (glucose 3 glucose-6-phosphate [G6P] 3 glucose-1-phosphate 3 uridine 5Ј-diphosphate [UDP] glucose 3 glycogen) and indirect (three carbon unit 3 phosphoenolpyruvate 3 G6P 3 glucose-1-phosphate 3 UDP glucose 3 glycogen) pathways (2). After oral glucose ingestion in the healthy human, 50 -77% of the liver glycogen synthesized is derived via the direct pathway (3-6). The response of the conscious dog is similar to that of humans, with 25-40% of a gastrointestinal glucose load being taken up by the liver and 50 -62% of accumulated hepatic glycogen being synthesized via the direct pathway (7-9).Individuals with diabetes exhibit excessive postprandial hyperglycemia, with a defect in meal-or glucose-induced suppression of endogenous glucose production (10 -15). Only a few studies have examined the effect of type 2 diabetes on splanchnic glucose uptake, and the results from these data are not concordant. Several studies (12,13,15,16) have demonstrated that the greater net splanchnic glucose rel...

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Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

et al. 2002

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“…Such gradients have been measured directly in animals in response to an intragastric glucose load. Intragastric administration of glucose to animals causes an immediate increase in portal vein glucose concentration, greater than that shown in the systemic arterial circulation, creating a positive portal arterial glucose concentration gradient [35,36,37] which can last for up to 60 min and is then lost as the glucose concentration in the portal vein falls [38]. In our study we can assume that the U 13 C 6 glucose appears in the systemic circulation slightly later than any appearance of glucose in the portal system, indicating a positive portal arterial glucose concentration gradient at the time of inducing hypoglycaemia as the tracer levels in the circulation are increasing.…”

Section: Discussionmentioning

confidence: 99%

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man

et al. 2002

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Aims/hypothesis. The role of glucose sensing cells in the human hepatic portal system in the initiation of the neuroendocrine responses to acute hypoglycaemia is not known. We investigated the effect of raising blood glucose concentrations in the hepatic-portal vein on neurohumoral responses during induction of systemic hypoglycaemia in nine healthy male volunteers. Methods. Each subject received an insulin infusion (3 mU·kg -1 ·min -1 ) on two occasions, in random order. Variable rate glucose infusion was used to maintain plasma glucose at 5 mmol/l for 60 min, then 3.2 mmol/l for 60 min. At 20 min prior to hypoglycaemia, subjects drank 20 g of glucose in water or water sweetened with saccharin. In five of the volunteers, the oral glucose was labelled with U-13C6 glucose, which showed peak systemic glucose absorption between 90 and 110 min. Five volunteers also repeated the study with a euglycaemic clamp.Results. Oral glucose was associated with a reduction in the early adrenaline response to hypoglycaemia, the area under the curve from 90 to 110 min falling from 24.02±20.84 (means ± SD) to 15. vere hypoglycaemia during the pharmacological treatment of diabetes mellitus. The inability to generate or detect the warning symptoms of early hypoglycaemia puts diabetic patients at high risk of episodes of severe hypoglycaemia [1] and often the fear of hypoglycaemia limits the optimisation of glycaemic control [2]. Associated with loss of subjective awareness of hypoglycaemia is a lowering of the glucose concentration required to initiate the counterregulatory response to hypoglycaemia, as well as a reduction in the magnitude and intensity of the counterregulatory response at any given blood glucose concentration [3,4,5]. The speculation that these defects are principally the result of defective glucose sensing gains support from data showing similar changes in the neuroendocrine rePerception of a minor decrease in plasma glucose concentration and initiation of a counterregulatory response are essential factors in the defence against se-

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“…The use of anaesthesia in this type of experiment is widespread (Fafournoux, Remesy & Demigne, 1983;Niewoehmer & Nuttall, 1988). The use of different sets of animals for the calculation of metabolite balances in the rat is the only reliable technique available at present (Smadja, Morin, Ferre & Girard, 1988;Niewoehmer & Nuttall, 1989), since no hepatic vein chronic catheterization technique has been developed.…”

Section: Discussionmentioning

confidence: 99%

Rat splanchnic net oxygen consumption, energy implications.

Casado

López

Esteve

et al. 1990

The Journal of Physiology

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SUMMARY1. The blood flow, Po,, pH and Pco2 have been estimated in portal and suprahepatic veins as well as in hepatic artery of fed and overnight starved rats given an oral glucose load. From these data the net intestinal, hepatic and splanchnic balances for oxygen and bicarbonate were calculated. The oxygen consumption of the intact animal has also been measured under comparable conditions.2. The direct utilization of oxygen balances as energy equivalents when establishing the contribution of energy metabolism of liver and intestine to the overall energy expenses of the rat, has been found to be incorrect, since it incorporates the intrinsic error of interorgan proton transfer through bicarbonate. Liver and intestine produced high net bicarbonate balances in all situations tested, implying the elimination (by means of oxidative pathways, i.e. consuming additional oxygen) of high amounts of H+ generated with bicarbonate. The equivalence in energy output of the oxygen balances was then corrected for bicarbonate production to 11-54 % lower values.3. Intestine and liver consume a high proportion of available oxygen, about onehalf in basal (fed or starved) conditions and about one-third after gavage, the intestine consumption being about 15 % in all situations tested and the liver decreasing its oxygen consumption with gavage.

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Relationship of Hepatic Glucose Uptake to Intrahepatic Glucose Concentration in Fasted Rats After Glucose Load

Cited by 41 publications

References 41 publications

Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man

Rat splanchnic net oxygen consumption, energy implications.

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