Role of the liver in Glucose Metabolism

HI!! subha here .. Today lets see about liver's glucose metabolism - so we can learn base about how diabetes kind of disease are evolving ....

Glucose metabolism 

- liver will capable of both storing and producing glucose . because of this  liver plays key role in maintaining the normal plasma glucose levels ~ 5mmol/L

- glucose pool in the body is around 60 mmol/L, with food we may ingest upto 3000 mmol/day , muscles may remove up to 250 mmol/hour when we exercise

- efficient buffering system is required to prevent excessive and dangerous glucose excursions 

- while the insulin sensitive tissue they are adipose tissue and muscle will  express the glucose transporter , may help to get rid of the most of the glucose arriving from gut to the liver  and to a small extent to the kidneys are the only organs that can produce glucose when needed 

- when glucose is absorbed from the gut, some of it may taken up by the liver, entering the hepatocyte from the sinusoids via the so-called GLUT-2 transporter 

- GLUT-2  has its half maximal transport capacity around the glucose concentration normally found in plasma this transporter is not regulated by insulin 

- upon entry, the glucose is phosphorylated by the enzyme glucokinase and may now either undergo glycolysis, or there is enough of it participate in the synthesis of glycogen, 

-  The liver may store up to 10% of its weight as glycogen, in addition the pyruvate generated from glycolysis in the liver cells, may be converted into Acetyl coA and participate in de novo lipogenesis 

- Thus a high intake of glucose may fill up the liver with glycogen as well as triglyceride droplets, normally both depots are rapidly mobilized after only 24 hours of fast almost all of the glycogen is exhausted and the liver fat may also be depleted after just a few days of fasting ( we should understand why fasting is important )

- Continued excessive nutrient intake may also lead to excessive lipid production in the liver cells, and when the content exceeds about 5.5% we talk about steatosis.  and this may reach extreme degrees and we know that from fatty goose liver, foire gras. steastosis is normally reversible, but may lead to liver disease 

- Excessive glycogen storage is only observed in glycogen storage diseases where glycogen mobilization is deffective. the processes of glycogen formation and de novo lipogenesis are both stimulated by insulin  the well known harmone from the pancreatic islets which reaches the liver with the portal of blood in high concentration. here it intracts with insulin receptors on the hepatocytes and stimulates glycolysis, the deposition of glucose and lipogenesis. 

- In the post absorptive phase, circulating glucose concentrations revert back to the normal fasting levels. and the nutition stimulated secretion of insulinotrophic gut harmone like GLP-1 and GIP ceases 

- Therefore, insulin levels also fall back to fasting levels. which means the liver uptake of glucose now stop. however, the various tissue of the body the red blood cells and the central nervous system all require glucose for energy production. 

- The central nervous system, for instance uses about 50% of the pool of glucose per hour. and this would causes plasma glucose concentration to fall where it not because the liver now start to produce glucose .

- This process is stimulated by on one hand the following insulin concentration  and other hand  the secretion glucogon - pancreatic islets 

- The hepatocyte express numerous glucogon receptors. activaition of these leads to a breakdown of stored glycogen, glycogenolysis  indeed important part of the liver glucose production in the fasting state is due to glucogons 

- Glucogenesis from lactate is relevant during strenous muscular exercise where large amount of lactate are generated from anaerobic glycolysis in the muscles .during fasting however the amino acid and glycerol are more important 

- The amino acid are derived from protein of the body in particular muscles where the protein are broken down , under the influence of cortisol, a harmone which is essential for providing substrates for glucogenesis 

- noradrenaline, adrenaline and low insulin level together , increases the hydrolysis of stored triglycerol in a porcess called lipolysis

- During, prolonged fasting ketone bodies provide important fuel for the CNS, which is able to adapt fuel during starvation, the heart and other muscles can likewise uses ketone bodies