Abstract
The liver is an organ with many facets, including a role in energy production and metabolic balance, detoxification and extraordinary capacity of regeneration. Hepatic glucose production plays a crucial role in the maintenance of normal glucose levels in the organism i.e. between 0.7 to 1.1 g/l. The loss of this function leads to a rare genetic metabolic disease named glycogen storage disease type I (GSDI), characterized by severe hypoglycemia during short fasts. On the contrary, type 2 diabetes is characterized by chronic hyperglycemia, partly due to an overproduction of glucose by the liver. Indeed, diabetes is characterized by increased uptake/production of glucose by hepatocytes, leading to the activation of de novo lipogenesis and the development of a non-alcoholic fatty liver disease. In GSDI, the accumulation of glucose-6 phosphate, which cannot be hydrolyzed into glucose, leads to an increase of glycogen stores and the development of hepatic steatosis. Thus, in these pathologies, hepatocytes are subjected to cellular stress mainly induced by glucotoxicity and lipotoxicity. In this review, we have compared hepatic cellular stress induced in type 2 diabetes and GSDI, especially oxidative stress, autophagy deregulation, and ER-stress. In addition, both GSDI and diabetic patients are prone to the development of hepatocellular adenomas (HCA) that occur on a fatty liver in the absence of cirrhosis. These HCA can further acquire malignant traits and transform into hepatocellular carcinoma. This process of tumorigenesis highlights the importance of an optimal metabolic control in both GSDI and diabetic patients in order to prevent, or at least to restrain, tumorigenic activity during disturbed glucose metabolism pathologies.
Highlights
Diabetes is characterized by increased uptake/production of glucose by hepatocytes, leading to the activation of de novo lipogenesis and the development of a non-alcoholic fatty liver disease
Both glycogen storage disease type I (GSDI) and diabetic patients are prone to the development of hepatocellular adenomas (HCA) that occur on a fatty liver in the absence of cirrhosis
Normoglycemia is maintained by endogenous glucose production (EGP), a process occurring in the liver, as well as in the kidneys and in the intestine [1]
Summary
Diabetes is characterized by increased uptake/production of glucose by hepatocytes, leading to the activation of de novo lipogenesis and the development of a non-alcoholic fatty liver disease. In the liver, dissociating the exact mechanisms behind cell stress induced by glucose toxicity or by lipid toxicity, such as in diabetic and/or obese patients is very difficult. Even if glucose uptake is impaired in obese/diabetic mice [13], elevated levels of blood glucose induce an increased metabolic flux downstream of G6P and a subsequent activation of de novo lipogenesis (Figure 2) [14].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
