Insulin exerts a variety of regulatory metabolic effects in a healthy human. The

Question

Insulin exerts a variety of regulatory metabolic effects in a healthy human. These effects are disrupted in diabetic patients.

a) Describe the signalling pathway by which insulin promotes the storage of glucose as glycogen in the liver of a healthy person.

b) Describe how insulin exerts its effects on glycolysis, gluconeogenesis and fatty acid synthesis in the liver of a healthy person.

c) Explain how an excess of triacylglycerols leads muscle cells to become resistant to insulin.  

d) What is known of the genetic and epigenetic factors that increase a person’s risk of developing diabetes?

(300-500 words in total)
         

Explanation / Answer

a) After consumption of carbohydrate rich diet, increase level of blood glucose is sensed by the pancreas, which leads to the synthesis of insulin from the islets of langerhans. This insulin enters into the bloodstream and bind to the membrane spaning glycoprotein receptors. Insulin consists of an extracellular domain, made from two alpha chains and an intracellular catalytic domain consisting two beta chains. Binding of insulin to the extracellular domain, activates tyrosine kinase activity of intracellular domain. Activite tyrosine kinase causes phosphorylation of MAP-Kinase and PI-3K (phosphatidylinositol 3 kinase). Activation of PI-3K leads to crucial metabolic functions including synthesis of glycogen. When glucose bound GLUT-4 transporter enters inside a cell, PI3K releases glucose from this transporter nd the excess amount is used to form glycogen.

b) glycosis- stimulated by insulin; gluconeogenesis-inhibited by insulin; fatty synthesis- stimulated by insulin.

c) Adiponectin is a adipose derived hormone. There is inverse relationship between the levels of adiopnectin and TAGs. Increased levels of TAG, decreases the expression of adiponectin which results into insulin resistance.

d) Epigenetic factors: Includes histone posttranslational modifications, non coding RNA, DNA methylation. E.g increase expression of miRNA in regulatory T cells, altered methylation and acetylation patterns of HLA genes, CTL cell etc.

Genetic factors:Includes HLA,IL-10, IF1H1, CTLA4. E.g. Increased cytokinine mediated beta cells destruction, modification of tymic expression of insulin and affecting recognisition by CTL etc.

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