Insulin W3 Flashcards
Insulin
• Insulin is the main hormone involved in glucose metabolism. Also important in control of supply storage of fats and protein
• Insulin is a peptide hormone. It consists of 2 chains – α and β - linked by S-S bonds.
• Acts at tyrosine kinase receptors
• Secreted from β-cells in the Islets of Langerhans in the endocrine pancreas (β-cells are the most abundant cell type in the Islets) into the hepatic portal vein
Insulin synthesis
synthesized as a pro- peptide by ribosomes on the RER
• Processing involves:
– Folding and formation of disulphide bonds
– Removal of the C peptide (31αα) to give 2 chains (A - 21αα and B
30αα) linked by disulphide bonds
• C peptide as well as insulin is secreted (Plasma C peptide level is a measure of insulin secretion as, unlike insulin, it is not cleared rapidly from the blood)
• It is stored until secretion is stimulated
Control of insulin secretion - the major factor
major control factor for insulin secretion is level of blood glucose – a simple negative feedback pathway
– After a meal glucose concentration increases
– Glucose diffuses into the pancreatic β-cell (via GLUT-2)
– Increased glucose concentration in the cell causes secretion of
insulin
– Insulin causes a decrease in blood glucose
– Decreased glucose in the β-cell decreases insulin secretion
Control of insulin secretion - other factors influencing secretion
Other factors can influence secretion including:
– Some amino acids (leucine, arginine)
– Autonomic nervous system (parasympathetic increases;
sympathetic decreases)
– Some gut hormones (incretins) - secreted in the GI tract in
response to food eg. GLP1
Actions of insulin
- secreted following a meal due to increased BG
- acts at tyrosine kinease coupled receptors
- acts to decrease BG (and fatty acids and aminos)
- decreases BG by increasing the uptake of into cells and utilisation of glucose
- promotes storage of fuel mols
Major target organs
Liver
Skeletal muscles
Adipose tissue
Liver and insulin
insulin is secreted into the hepatic portal vein, transporting it directly to the liver. Liver removes 60% of the insulin before it enters the systemic
circulation
Actions of Insulin – Glucose Homeostasis
Insulin lowers blood glucose by:
– increase glucose uptake into cells (skeletal muscle and adipose tissue)
– increase glycogenesis in the liver and skeletal
muscle
– decrease glycogenolysis
– decrease gluconeogenesis
– increase glycolysis
Increased uptake of glucose is mediated by….
the insulin-dependant facilitated glucose h transporter, GLUT-4
What does glucose require t move through the plasma membrane
Aa transporter
What dos GLUT transporters allow
Facilitated diffusion of glucose down its conc grad
What does GLUT-4 do in the presence of insulin
Moves from inside the cell to the cell membrane and therefore increases the uptake of glucose
Where is GLUT-4 abundant
Skeletal muscle and adipose tissue
Where is uptake by GLUT-2
Liver
GLUT-2
Not insulin dependant
Action of insulin in fats and proteins
Lowers blood fatty acids and increases triglyceride synthesis
- increases fatty acid uptake into adipose tissues
- increases uptake of glucose into adipose where it is used for de novo synthesis of fatty acids and glycerides
- decreases lipolysis
Action of insulin in fats and proteins - after meal
Lowers blood amino acids and increases protein synthesis
- increases uptake of amino acids into cells
- increase protein synthesis
- decrease protein degradation