Inosine released after hypoxia activates hepatic glucose liberation through A<sub>3</sub>adenosine receptors

Guinzberg, Raquel; Cortés, Daniel; Dı́az-Cruz, Antonio; Riveros‐Rosas, Héctor; Villalobos‐Molina, Rafael; Piña, Enrique

doi:10.1152/ajpendo.00173.2005

Cited by 52 publications

(46 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Adenosine and its receptors regulate a variety of hepatic and hepatocellular functions, including glucose release (34,35), protein synthesis (36), glutathione synthesis (37), hepatic regulation of renal Na + and water excretion, and portal blood flow (18,(38)(39)(40). Moreover, ethanol-and acetate-induced adenosine release mediates many of these effects.…”

Section: Discussionmentioning

confidence: 99%

Adenosine signaling contributes to ethanol-induced fatty liver in mice

Peng¹,

Borea²,

Wilder³

et al. 2009

J. Clin. Invest.

150

View full text Add to dashboard Cite

Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the biochemical and pharmacological mechanisms by which ethanol stimulates these molecular changes remain unknown. During ethanol metabolism, adenosine is generated by the enzyme ecto-5′-nucleotidase, and adenosine production and adenosine receptor activation are known to play critical roles in the development of hepatic fibrosis. We therefore investigated whether adenosine and its receptors play a role in the development of alcohol-induced fatty liver. WT mice fed ethanol on the LieberDeCarli diet developed hepatic steatosis, including increased hepatic triglyceride content, while mice lacking ecto-5′-nucleotidase or adenosine A 1 or A 2B receptors were protected from developing fatty liver. Similar protection was also seen in WT mice treated with either an adenosine A 1 or A 2B receptor antagonist. Steatotic livers demonstrated increased expression of genes involved in fatty acid synthesis, which was prevented by blockade of adenosine A 1 receptors, and decreased expression of genes involved in fatty acid metabolism, which was prevented by blockade of adenosine A 2B receptors. In vitro studies supported roles for adenosine A 1 receptors in promoting fatty acid synthesis and for A 2B receptors in decreasing fatty acid metabolism. These results indicate that adenosine generated by ethanol metabolism plays an important role in ethanol-induced hepatic steatosis via both A 1 and A 2B receptors and suggest that targeting adenosine receptors may be effective in the prevention of alcohol-induced fatty liver. IntroductionFatty liver is the most common and earliest response of the liver to heavy alcohol consumption and may develop into alcoholic hepatitis and fibrosis. Although fatty liver is a very common medical problem and the molecular events involved in the pathogenesis of fatty liver are well understood, the connection between ethanol ingestion and metabolism and the activation of the events involved in the development of hepatic steatosis is not well understood.

show abstract

Section: Discussionmentioning

confidence: 99%

Adenosine signaling contributes to ethanol-induced fatty liver in mice

Peng¹,

Borea²,

Wilder³

et al. 2009

J. Clin. Invest.

150

View full text Add to dashboard Cite

show abstract

“…In adipose tissue (A1-subtype receptors), caffeine could result in increased lipolysis and a glucose-saving systemic effect (3,19,24,25,27,38); however, by antagonizing adenosine receptors on skeletal muscle (also A1-subtype receptors), caffeine increases glycolysis (27). In addition, adenosine receptors in Exercise and caffeine in diabetic ratsthe liver stimulate gluconeogenesis, glycogenolysis, and glucose release (14,15,18,21,27,36), all of which could be potentially antagonized by caffeine.…”

Section: Discussionmentioning

confidence: 99%

Exercise partially reverses the inhibitory effect of caffeine on liver gluconeogenesis in type 1 diabetic rats with hypoglycemia

Gilglioni

Ghuidotti

Vilela

et al. 2016

Physiology International

View full text Add to dashboard Cite

The purpose was to determine the possible effects of exercise and/or caffeine on hypoglycemia and liver gluconeogenesis in diabetic rats. These were divided into four subgroups: (a) intraperitoneal insulin only, (b) exercise bout before insulin, (c) caffeine after insulin, and (d) exercise bout before and caffeine after insulin. The marked glycemic drop 45 min after insulin (0 min = 229.00, 45 min = 75.75) was considerably reduced (p < 0.05) by caffeine or exercise (45 min: exercise = 127.00, caffeine = 104.78). However, this systemic effect was lost (p > 0.05) when they were combined (45 min: exercise + caffeine = 65.44) (Mean, in mg·dL). Caffeine alone strongly inhibited liver glucose production from 2 mM lactate 45 min after insulin (without caffeine = 3.05, with caffeine = 0.27; p < 0.05), while exercise + caffeine partially re-established the liver gluconeogenic capacity (exercise + caffeine = 1.61; p < 0.05 relative to the other groups) (Mean, in μmol·g −1 ). The improved hypoglycemia with caffeine or exercise cannot be explained by their actions on liver gluconeogenesis. As their beneficial effect disappeared when they were combined, such association in diabetic patients should be avoided during the period of hyperinsulinemia due to the risk of severe hypoglycemia.

show abstract

“…Ectonucleotidase-derived AMP does not act as an agonist, but its degradation product, adenosine, is a natural agonist for ARs. Inosine, formed by the deamination of adenosine, has also been shown to have agonist activity at ARs (Guinzberg et al, 2006).…”

Section: Introductionmentioning

confidence: 99%