The substrates for glyconeogenesis include lactate, pyruvate, amino acids, glycerol and propionate. The predominant source of carbon atoms for glucose synthesis is lactate. This process is done by gluconeogenesis. Pyruvate is generated in muscle and other peripheral tissues. This can be transaminated to alanine. This inturn is returned to the liver for the purpose of gluconeogenesis. This pathway is known as glucose-alanine cycle. According to the metabolism of amino acids, all the amino acids except lysine and leucine can be despoiled in to TCA cycle.
This process results in the production of pyruvate which can be used by the gluconeogenic pathway. For the process of gluconeogenesis, the glyceraol backbone of lipids can be used . The gluconeogenesis in diabetic patients and non-patients is totally different. Using the mathematical model of the krebs cycle, we can estimate gluconeogenesis. In healthy volunteers, the hepatic glucose output was approximately 97% and when compared with non-insulin dependent diabetes mellitus and non diabetic patients, the gluconeogenesis was increased threefold in non-insulin dependent diabetes mellitus.
Diabetes type I is a very dangerous disease where secretion of insulin totally fails. The complete lack of insulin leads to two metabolic process. Firstly, increase in the lipolysis in adipose tissue and inspite of high plasma gluco levels, there is activation of hepatic gluconeogenesis. The increase in fatty acids results in harmone-sensitive lipase. This follows lack of insulin inhibition. This, then leads to ketoacidosis. Thjs is very dangerous and coma and death is followed by ketoacidosis. In diabetes, blood glucose levels may increase many folds.
Instead of this, hepatic gluconeogenesis become activated using amino acids as substrate. This is due to insulin as insulin is the most important inhibitor of gluconeogenesis. The high levels of glucose which we can find in diabetes type I and II is very dangerous. Due to the increased level of glucose sorbitol is formed in the lens of the eye, disturbing protein synthesis and increase osmotic pressure. The venomous effect of glucose is glycation of proteins. The circulatory and neurological defects which follow diabetes are due to glycation. The type II diabetic mellitus is prevalent worldwide due to obesity.
Hyperglycaemia is the reason for diabetes and this is because of the high level of hepatic gluconeogenesis. The medial hypothalamus plays an important role in the regulation of energy balance and modulation of liver glucose. To lower blood glucose levels, activation of ATP-sensitive potassium channels in mediobasal hypothalamus is required. This process is done through hepatic gluconeogenesis. The surgical resection of the hepatic branch of the vagus nerve, infusion of KATP blocker with mediobasal hypothalamus stops the effect of systemic insulin, central insulin on hepatic glucose production.
Through this, we can say that the creation of hypothalamic KATP channels restrains hepatic glyconeogenesis and this result in diabetic hyperglycaemia. To maintain the glucose homeostatis, hepatic gluconeogenesis plays an important role. This process is stimulated by glucagon in which adiponectin and insulin are inhibitory. AMPK and insulin increase the phosphorylation of TORC2 as an essential component of gluconeogenesis. TORC2 is considered as gluconeogenic molecular switch which senses cellular energy status and hormones. Diabetes can only be controlled but not cured permanently.
The treatment depends on the amount of insulin the body makes and the ability of the body to use insulin. Type 2 diabetes can be controlled by losing weight, exercising regularly and eating healthy diet. Pills also can be used to boost the natural insulin or use the insulin efficiently. Treatment for diabetes is nothing but keeping the blood sugar levels steady. If the body cannot produce insulin totally, then insulin shots are necessary. For type II diabetes, like metformin, gluconeogenesis is used for the therapy where formation of glucose is inhibited stimulate glucose uptake by cells. Metformin is used as the anti-diabetic drug.
In this way, Gluconeogenesis is very important for the production of glucose in the body. REFERENCES: Byrant Miles, Gluconeogenesis, January 31, 2003. http://www. tamu. edu/classes/bmiles/lectures/gluconeogenesis. pdf Vijay Aswani, How well do you understand blood glucose levels? September 19, 2002. http://www. medscape. com/viewarticle/438144_print 3. Diabetes symptoms-prevention is better than cure, 2009 http://www. diabitieslife. com/diabetes/symptoms-of-diabetes/identify-diabetes/diabetes-symptoms-prevention-is-better-than-cure. htm 4. Introduction, January 27, 2009. http://themedicalbiochemistrypage. org/gluconeogenesis. html