Actions of glucagon on flux rates in perfused rat liver

Mauch, Teri Jo; Scholz, Roland

doi:10.1111/j.1432-1033.1983.tb07785.x

Cited by 20 publications

(9 citation statements)

References 26 publications

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“…The consumption rate for the small intestine compared well with results obtained in intestinal perfusions with red blood cells [6,[10][11][12]. In isolated liver perfusions with erythrocyte-free media the oxygen uptake was between 2 and 2.5 ,mol/min per g [13][14][15][16][17][18].…”

Section: Functional and Morphological Integrity Of The Intestine-livementioning

confidence: 54%

Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat

Gardemann

Watanabe

Große

et al. 1992

Biochemical Journal

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1. Previous studies have shown that an arterial-to-portal glucose concentration gradient may be an important signal for insulin-dependent net hepatic glucose uptake. It is not known whether intestinal factors also contribute to the regulation of hepatic glucose utilization. This problem was studied in a newly developed model which allows luminal perfusion of the small intestine via the pyloric sphincter and a combined vascular perfusion of the small intestine via the gastroduodenal artery and superior mesenteric artery, and of the liver via the hepatic artery and portal vein. 2. In both the presence and the absence of 1 mM-glutamine in the vascular perfusate, only about 7% of a luminal bolus of 5500 mumol (1 g) of glucose was absorbed by the small intestine, and nothing was taken up by the liver. 3. With small doses of 75-380 mumol (11-55 mg) of luminal glutamine, but not with 300 mumol of alanine, the intestinal absorption of the luminal glucose bolus was increased almost linearly from 7% to a maximum of 40% and the hepatic uptake from 0% to a maximum of 22%. 4. The increase of hepatic glucose uptake caused by luminal glutamine was only observed when the glucose load was applied into the intestinal lumen, rather than into the superior mesenteric artery. 5. The relative hepatic glucose uptake (uptake/portal supply) was enhanced from 0% to 55% with an increase in portal supply by luminal glutamine, whereas with a similar range of portal glucose supply the relative hepatic uptake by the isolated liver, perfused simultaneously via the hepatic artery and portal vein, was slightly decreased, from 20% to 15%. 6. Addition of various amounts of portal glutamine and/or alterations in the Na+ content of the portal perfusate failed to mimic the luminal glutamine-dependent activation of hepatic glucose uptake. Therefore the luminal-glutamine-elicited activation of hepatic glucose uptake was apparently not caused by a simple increase in the portal-arterial glucose gradient, by glutamine itself or by Na(+)-dependent alterations in hepatic cell volume. The results suggest that luminal glutamine caused not only an increase in intestinal glucose absorption by unknown mechanisms but also the generation of one or more humoral or nervous 'hepatotropic' signals in the small intestine which enhanced the hepatic uptake of absorbed glucose.

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Section: Functional and Morphological Integrity Of The Intestine-livementioning

confidence: 54%

Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat

Gardemann

Watanabe

Große

et al. 1992

Biochemical Journal

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“…Exercise, for example, is associated with a large increase in portal venous glucagon. Glucagon increases hepatic glucose production (Hirsch et al, 1991; Lavoie et al, 1997; Wasserman et al, 1989, 1985, 1984), fat oxidation (Wasserman et al, 1995), amino acid metabolism (Halseth et al, 1998; Wasserman et al, 1988), and ureagenesis (Exton and Park, 1966; Heimberg et al, 1969; Kimmig et al, 1983; Krishna et al, 2000). More recently we showed that elevated glucagon increases the AMP/ATP ratio and activates AMPK in vivo (Berglund et al, 2011, 2009).…”

Section: Endocrine Actionmentioning

confidence: 99%

“…Glucagon is elevated and AMPK is activated under conditions uptake (Kimmig et al, 1983) and fat oxidation (Heimberg et al, 1969) are elevated. The coupled relationship in which O 2 between TCA cycling and gluconeogenesis is paralleled by a coupling of ATP formation and breakdown.…”

Section: Endocrine Actionmentioning

confidence: 99%

Emerging role of AMP-activated protein kinase in endocrine control of metabolism in the liver

Hasenour

Berglund

Wasserman

2013

Molecular and Cellular Endocrinology

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This review summarizes the emerging role of AMP-activated protein kinase (AMPK) in mediating endocrine regulation of metabolic fluxes in the liver. There are a number of hormones which, when acting on the liver, alter AMPK activation. Here we describe those hormones associated with activation and de-activation of AMPK and the potential mechanisms for changes in AMPK activation state. The actions of these hormones, in many cases, are consistent with downstream effects of AMPK signaling thus strengthening the circumstantial case for AMPK-mediated hormone action. In recent years, genetic mouse models have also been used in an attempt to establish the role of AMPK in hormone-stimulated metabolism in the liver. Few experiments have, however, firmly established a causal relationship between hormone action at the liver and AMPK signaling.

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“…As shown in the following paper (Fig. 2 of [14]), the concentration for half-maximal effect was about three-times lower than that required for half-maximal inhibition of lactate plus pyruvate production. The data suggest that glycogen breakdown is more sensitive to stimulation than glycolysis to inhibition by glucagon.…”

Section: Experimental Protocolmentioning

confidence: 99%

Actions of glucagon on flux rates in perfused rat liver

Mauch

Kerzl

Schwabe

et al. 1983

European Journal of Biochemistry

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Changes in the rates of glucose, lactate and pyruvate production following infusion of glucagon were studied in isolated livers from fed or fasted rats perfused with non-recirculating Krebs-Henseleit bicarbonate buffer.1. Evidence was presented that under these experimental conditions, the release of lactate plus pyruvate into the perfusate represents 80 -90 % of the total glycolytic flux; oxidation of pyruvate derived from glucose and/or glycogen accounts for the remaining 10 -20 %, whereas recycling of pyruvate to glucose is negligible.2. In the presence of glucagon, rates of lactate plus pyruvate production were diminished to less than 30 % in the fed state (glycogen as substrate) and to less than 10 % in the fasted state (glucose as substrate). Rates of pyruvate oxidation were unchanged. Although recycling of pyruvate to glucose was enhanced, it could account for not more than 20 % of the decrease in lactate plus pyruvate production. The data indicate a strong inhibition of the substrate flux through glycolysis.3. The glucagon concentration for half-maximal inhibition of glycolysis was 0.2 nM, independent of the substrate (glucose or glycogen) and the nutritional state. The effective concentrations were within the physiological range of glucagon concentrations reported for portal venous blood.4. Transient state analyses indicated that the inhibition of glycolysis precedes the stimulation of glycogenolysis. When after a delay glycogenolysis was accelerated, it was followed by a transient stimulation of glycolysis. The stimulatory component in the glucagon effect on glycolysis was diminished in glycogen-depleted livers and when glucose was the main substrate. The coordinated control of glycolysis and glycogenolysis by glucagon and the interaction of the two processes in the transient state are discussed.It is well known that glucagon stimulates hepatic glycogenolysis and that this phenomenon is due to a cyclic-AMPmediated activation of enzymes involved in glycogen breakdown [l -31. It was also reported that glucagon, in addition to its long-term effects, causes a rapid inactivation of key enzymes of glycolysis [4-71. Based on these findings, the inhibition of glycolytic flux by glucagon became textbook knowledge. A direct proof, however, was missing until now.In this communication, we describe the dose-response and the kinetics of the short-term effects of glucagon on rates of glycolysis and glycogenolysis in livers from fed and fasted rats. The isolated liver perfused with non-recirculating medium is a suitable model for the study of flux rates. Since metabolites do not accumulate in the perfusate, metabolite rates can be determined directly from the metabolic concentrations in the effluent perfusate. The release of glucose, lactate and pyruvate, therefore, should provide an estimate of rates of carbohydrate degradation. We present evidence that under our experimental Enzymes. Phosphofructokinase or ATP : ~-fructose-6-phosphate 1-phosphotransferase (EC 2.7.1.1 1); phosphofructokinase 2, PFK2 or ATP : ~-fructo...

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Actions of glucagon on flux rates in perfused rat liver

Cited by 20 publications

References 26 publications

Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat

Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat

Emerging role of AMP-activated protein kinase in endocrine control of metabolism in the liver

Actions of glucagon on flux rates in perfused rat liver

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