scholarly journals Endocannabinoid System in Hepatic Glucose Metabolism, Fatty Liver Disease, and Cirrhosis

2019 ◽  
Vol 20 (10) ◽  
pp. 2516 ◽  
Author(s):  
Ivonne Bazwinsky-Wutschke ◽  
Alexander Zipprich ◽  
Faramarz Dehghani
Keyword(s):  
Insulin Resistance ◽  
Portal Hypertension ◽  
Liver Disease ◽  
Glucose Metabolism ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Expression Patterns ◽  
Endocannabinoid System ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose

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.

Mechanisms of the free fatty acid-induced increase in hepatic glucose production

2003 ◽  
Vol 284 (5) ◽  
pp. E863-E873 ◽  
Author(s):  
Tony K. T. Lam ◽  
André Carpentier ◽  
Gary F. Lewis ◽  
Gérald van de Werve ◽  
I. George Fantus ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Recent Progress ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Controversial Issues ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose

The associations between obesity, insulin resistance, and type 2 diabetes mellitus are well documented. Free fatty acids (FFA), which are often elevated in obesity, have been implicated as an important link in these associations. Contrary to muscle glucose metabolism, the effects of FFA on hepatic glucose metabolism and the associated mechanisms have not been extensively investigated. It is still controversial whether FFA have substantial effects on hepatic glucose production, and the mechanisms responsible for these putative effects remain unknown. We review recent progress in this area and try to clarify controversial issues regarding the mechanisms responsible for the FFA-induced increase in hepatic glucose production in the postabsorptive state and during hyperinsulinemia.

scholarly journals Influence of Ang-(1-7) intervention on ACE2-Ang (1-7)-Mas pathway activity, hepatic glucose metabolism and insulin resistance in type-2 diabetic rats

2021 ◽  
Vol 18 (5) ◽  
pp. 995-999
Author(s):  
Yufang Liu ◽  
Fang Wang ◽  
Xiue Xu ◽  
Hui Cong ◽  
Guiyan Chen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Normal Control ◽  
Diabetic Control ◽  
Study Group ◽  
Control Groups ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose

Purpose: To study the effects of angiotensin-(1-7) (angiot (1-7) intervention on angiotensin converting enzyme (ACE)-angiot-(1-7)-Mas pathway, hepatic glucose metabolism, and insulin resistance in rats with type 2 diabetes. Methods: Thirty-six Sprague Dawley rats were randomly divided into normal control, diabetic control and study groups (12 rats per group). Rats in the normal group were fed normal feed, while rats in the observation and diabetic control groups were type-2 diabetes model, and were given subcutaneous injection of angiot-(1-7) for 8 weeks. Serum insulin resistance index (IRI) and fasting insulin (FINS) were assayed. Other parameters measured were the levels of ACE2 and Mas receptor mRNA in liver tissues. Results: The levels of FINS in the study and control groups decreased, relative to normal control, while the levels of IRI was elevated (p < 0.05). There were significant increases in study group levels of Mas and ACE2, while angiot-(1-7) was lower, relative to control group (p < 0.05). The expressions of ACE2 and Mas receptors in study and diabetic control rats groups were downregulated, when compared to normal control. The expressions of ACE2 and Mas receptors also decreased in the study group exposed to angiot-(1-7) (p < 0.05). Conclusion: Angiot-(1-7) significantly increases the levels of FINS and IR, improves hepatic glucose metabolism and enhances ACE2-angiot-(1-7)-Mas pathway. Thus, angiot-(1-7) may be a new drug candidate for the treatment of type 2 diabetes.

The regulation of glucose metabolism: implications and considerations for the assessment of glucose homeostasis in rodents

2014 ◽  
Vol 307 (10) ◽  
pp. E859-E871 ◽  
Author(s):  
Greg M. Kowalski ◽  
Clinton R. Bruce
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
Whole Body ◽  
Rodent Models ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Underlying Causes

The incidence of insulin resistance and type 2 diabetes (T2D) is increasing at alarming rates. In the quest to understand the underlying causes of and to identify novel therapeutic targets to treat T2D, scientists have become increasingly reliant on the use of rodent models. Here, we provide a discussion on the regulation of rodent glucose metabolism, highlighting key differences and similarities that exist between rodents and humans. In addition, some of the issues and considerations associated with assessing glucose homeostasis and insulin action are outlined. We also discuss the role of the liver vs. skeletal muscle in regulating whole body glucose metabolism in rodents, emphasizing the importance of defective hepatic glucose metabolism in the development of impaired glucose tolerance, insulin resistance, and T2D.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

Lack of effect of parathyroid hormone on hepatic glucose metabolism in the dog

Metabolism ◽  
1981 ◽  
Vol 30 (5) ◽  
pp. 469-475 ◽  
Author(s):  
S. Bevilacqua ◽  
E. Barrett ◽  
E. Ferrannini ◽  
R. Gusberg ◽  
A. Stewart ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Glucose Metabolism ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose
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