Commentary: Lactate-Induced Glucose Output Is Unchanged by Metformin at a Therapeutic Concentration—A Mass Spectrometry Imaging Study of the Perfused Rat Liver

Lactate has been found to enhance the formation of glycogen from both glucose and lactate as substrate (Z. Zhang and J. Radziuk. Biochem. J. 280: 415–419, 1991). To evaluate the relative importance of its role as substrate and regulatory factor, a dual dose-response evaluation was done by adding variable amounts of glucose and lactate to the medium in a recirculating perfused rat liver preparation. Nine groups of perfusions were performed utilizing three different levels of carbon infusion into the system: 0.25, 1.0, and 2.0 mg/min. These levels of carbon infusion were further subdivided into different relative amounts of glucose and lactate. Lactate uptake by the perfused liver was linearly related with net glucose output, regardless of the glucose concentrations. In contrast to this, the effect of lactate uptake on the rate of glycogen synthesis is saturable. Moreover, the rate of glycogen formation at which this saturation occurs is dependent only on the mean perfusate glucose concentration. The highest amount of glycogen formed in a 2-h period was 50 +/- 7 mg and the lowest 3.4 +/- 0.3 mg. A family of dose-response curves was generated describing this dual dependence of glycogen formation (both direct and gluconeogenetic pathways) on lactate and glucose.

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Glyburide Sensitizes Perfused Rat Liver to Insulin-Induced Suppression of Glucose Output

Diabetes ◽

10.2337/diab.36.4.472 ◽

1987 ◽

Vol 36 (4) ◽

pp. 472-476 ◽

Cited By ~ 14

Author(s):

O. P. McGuinness ◽

D. R. Green ◽

A. D. Cherrington

Keyword(s):

Rat Liver ◽

Perfused Rat Liver ◽

Glucose Output

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Effects of insulin and adenosine 3',5'-monophosphate on K+ flux and glucose output in perfused rat liver

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1971.221.6.1645 ◽

1971 ◽

Vol 221 (6) ◽

pp. 1645-1651 ◽

Cited By ~ 32

Author(s):

TF Williams ◽

JH Exton ◽

N Friedmann ◽

CR Park

Keyword(s):

Rat Liver ◽

Perfused Rat Liver ◽

Glucose Output

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Concomitant stimulation by vasopressin of biliary and perfusate calcium fluxes in the perfused rat liver

Biochemical Journal ◽

10.1042/bj2810387 ◽

1992 ◽

Vol 281 (2) ◽

pp. 387-392 ◽

Cited By ~ 8

Author(s):

Y Hamada ◽

A Karjalainen ◽

B A Setchell ◽

J E Millard ◽

F L Bygrave

Keyword(s):

Oxygen Uptake ◽

Rat Liver ◽

Bile Flow ◽

Bile Secretion ◽

Perfused Rat Liver ◽

Diseased Liver ◽

Glucose Output ◽

Opposing Effects ◽

Prior Administration ◽

Slow Onset

Changes in perfusate Ca2+ (measured with a Ca(2+)-selective electrode) and changes in bile calcium (measured by atomic absorption spectroscopy) were continuously and simultaneously monitored after infusion of (a) vasopressin, (b) glucagon and (c) both vasopressin and glucagon together to the perfused rat liver. Also monitored were perfusate glucose and oxygen concentrations and bile flow. Vasopressin induces a sharp, transient, pulse of increased bile flow and increased bile calcium within 1 min of infusion, concomitant with rapid changes in perfusate Ca2+ fluxes, glucose output and oxygen uptake. This is immediately followed by a decrease in both bile flow and bile calcium for as long as the hormone is administered. Changes induced by glucagon are a relatively slow onset of perfusate Ca2+ efflux and oxygen uptake, but rapid glucose output, and a small but significant and transient decrease in bile flow and bile calcium which, despite the continued infusion of the hormone, spontaneously and rapidly returns to normality. However, the greatest responses are observed after co-administration of both hormones. Coincident with the augmented perfusate Ca2+ fluxes (influx) seen in earlier work, there occurs within 1 min of vasopressin infusion a sharp increase in bile secretion and bile calcium greater in magnitude than that produced by vasopressin alone. Immediately thereafter bile secretion and bile calcium decline below basal values and remain there for as long as the hormones are administered. Glucagon and vasopressin therefore each have opposing effects on bile flow and bile calcium. However, the action of vasopressin is enhanced by the prior administration of glucagon. The data thus reveal features about the actions of glucagon and Ca(2+)-mobilizing hormones on bile flow and bile calcium not previously recorded and provide a novel framework around which the whole issue of hepato-biliary Ca2+ homoeostasis can be assessed in normal and diseased liver.

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The Effect of Combined Ischaemia and Acidosis on Lactate Uptake and Gluconeogenesis in the Perfused Rat Liver

Clinical Science ◽

10.1042/cs0600537 ◽

1981 ◽

Vol 60 (5) ◽

pp. 537-542 ◽

Cited By ~ 17

Author(s):

R. A. Iles ◽

R. D. Cohen ◽

P. G. Baron

Keyword(s):

Lactic Acid ◽

Rat Liver ◽

Hepatic Uptake ◽

Strenuous Exercise ◽

Perfused Rat Liver ◽

Lactate Uptake ◽

Glucose Output ◽

Rat Livers

1. Perfused rat livers were subjected to an acid perfusate and varying degrees of ischaemia in an attempt to simulate the conditions of strenuous exercise or shock. 2. Lactate uptake and glucose output from the liver decreased during moderate ischaemia alone and more so when, in addition, the perfusate was made acidic. 3. Hepatic ATP and ADP content increased in the presence of an acid perfusate. 4. It is concluded that both ischaemia and acidosis may contribute to the diminished hepatic uptake of lactic acid in strenuous exercise and shock.

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Stimulation of release of prostaglandin D2 and thromboxane B2 from perfused rat liver by extracellular adenosine

Biochemical Journal ◽

10.1042/bj2700039 ◽

1990 ◽

Vol 270 (1) ◽

pp. 39-44 ◽

Cited By ~ 22

Author(s):

S vom Dahl ◽

M Wettstein ◽

W Gerok ◽

D Häussinger

Keyword(s):

Rat Liver ◽

Portal Pressure ◽

Thromboxane B2 ◽

Adenosine Infusion ◽

Isolated Perfused Rat Liver ◽

Signal Molecules ◽

Prostaglandin D2 ◽

Perfused Rat Liver ◽

Glucose Output ◽

Stimulation Of

In isolated perfused rat liver, adenosine infusion (50 microM) led to increases in glucose output and portal pressure and a net K+ release of 3.7 +/- 0.21 mumol/g, which was followed by an equivalent net K+ uptake after cessation of the nucleoside infusion. These effects were accompanied by a transient stimulation of hepatic prostaglandin D2 and thromboxane B2 release. The Ca2+ release observed upon adenosine infusion (50 microM) was 23.5 +/- 5.2 nmol/g, i.e. 10-20% of the Ca2+ release observed with extracellular ATP (50 microM). Indomethacin (10 microM) prevented the adenosine-induced stimulation of glucose output and the increase in portal pressure by 79 and 63% respectively, and completely abolished the stimulation of prostaglandin D2 release. The thromboxane A2 receptor antagonist BM 13.177 (20 microM), the phospholipase A2 inhibitor 4-bromophenacyl bromide (20 microM) and the cyclo-oxygenase inhibitor ibuprofen (50 microM) also decreased the glycogenolytic and vasoconstrictive responses of the perfused rat liver upon adenosine infusion by 50-80%. When the indomethacin inhibition of adenosine-induced prostaglandin D2 release was titrated, a close correlation between prostaglandin D2 release and the metabolic and vascular responses to adenosine was observed. These findings suggest an important role for eicosanoids in mediating the nucleoside responses in the perfused rat liver. Since eicosanoids are known to be formed by non-parenchymal cells in rat liver [Decker (1985) Semin. Liver Dis. 5, 175-190], the present study gives further evidence for an important role of eicosanoids as signal molecules between the different liver cell populations.

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