There is growing evidence that
glucose metabolism in the liver is in part under the control of the
endocannabinoid system (ECS) which is also supported by its presence in this organ. The ECS consists of its
cannabinoid receptors (CBRs) and
enzymes that are responsible for
endocannabinoid production and metabolism. ECS is known to be differentially influenced by the hepatic
glucose metabolism and
insulin resistance, e.g.,
cannabinoid receptor type 1(CB1) antagonist can improve the
glucose tolerance and
insulin resistance. Interestingly, our own study shows that expression patterns of CBRs are influenced by the light/dark cycle, which is of significant physiological and clinical interest. The ECS system is highly upregulated during chronic
liver disease and a growing number of studies suggest a mechanistic and therapeutic impact of ECS on the development of
liver fibrosis, especially putting its receptors into focus. An opposing effect of the CBRs was exerted via the CB1 or
CB2 receptor stimulation. An activation of CB1 promoted fibrogenesis, while CB2 activation improved antifibrogenic responses. However, underlying mechanisms are not yet clear. In the context of
liver diseases, the ECS is considered as a possible mediator, which seems to be involved in the synthesis of fibrotic tissue, increase of intrahepatic vascular resistance and subsequently development of
portal hypertension.
Portal hypertension is the main event that leads to complications of the disease. The main complication is the development of variceal
bleeding and
ascites, which have prognostic relevance for the patients. The present review summarizes the current understanding and impact of the ECS on
glucose metabolism in the liver, in association with the development of
liver cirrhosis and hemodynamics in
cirrhosis and its complication, to give perspectives for development of new therapeutic strategies.