Role of Insulin and Glucagon in the regulation of metabolism



Role of Insulin and Glucagon in the regulation of metabolism

Wk 11 LOs

1. Outline the synthesis of insulin and its release into the circulation

• Insulin is a small molecule consisting of two amino acid chains linked by disulfide linkages

• It is synthesized in the beta cells of the Islets of Langerhans in the pancreas

• Ribosomes on the surface of the endoplasmic reticulum (ER) translate the insulin mRNA to form an insulin preprohormone (11.5 kDa).

• This is then cleaved in the ER to form proinsulin (~9 kDa).

• Most of this is then further cleaved in the Golgi apparatus to form mature insulin and a cleavage peptide, C peptide.

[pic]

• Both mature insulin and the C peptide are then packaged together into secretory granules and secreted into the blood stream together after physiologic stimulation.

Secretion of Insulin

• glucose enters the beta cells of the pancreas via GLUT2 transporters

• glucose is then phosphorylated by glucokinase, which traps it inside the cell, and is further metabolized to create ATP

• ↑ ATP causes ATP-gated K channel to close

• ↑ K+ ions inside the cell depolarizes the membrane and cause voltage gated Calcium channels to open

• the brisk increase in intracellular [calcium] causes the insulin storage granules to move to the surface of the cell and for insulin to be released via exocytosis

• the Islets of the pancreas are highly vascular and ensures prompt diffusion of insulin into the nearby blood vessels

• insulin secretion is biphasic; there is the initial release of insulin stores and then a second prolonged phase where new insulin has to be synthesized and packaged before release

[pic]

2. List the signals that trigger the release of (a) insulin and (b) glucagon from the islets

a) insulin

• high blood glucose levels (>5mmol/L)

• some GI hormones

• ↑ certain amino acids (leucine and arginine) after a protein rich meal

• glucagon

• parasympathetic nervous system and β-receptors of sympathetic nervous system

b) glucagon

• low blood glucose levels ( ................
................

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