Insulin and Diabetes Flashcards
What is diabetes?
Diabetes is a chronic health condition that affects how your body turns food into energy.
Glucose not correctly transported in muscles and adipose tissue.
Fat not correctly stored in adipose tissue.
How is insulin synthesised?
Synthesised in B-cells of the Islets of Langerhans in the pancreas.
Synthesised as a single polypeptide called pro-insulin
Hydrolysed at two points to form two chains, these are linked by disulphide bridges.
The “inactive” segment released by hydrolysis is termed the C-peptide.
How is insulin secreted?
Glucose is major stimulus to insulin secretion.
It enters the B cells via a non-insulin dependant transporter and is metabolised.
ATP is produced, this inactivates ATP-dependent hyperpolarising K+ channel. This channel becomes blocked so K+ can’t leave the cell. K+ accumulate at the cell membrane.
This leads to depolarisation of the B-cells.
Calcium-dependent channels release insulin.
What are some other stimuli of insulin secretion?
Parasympathetic vagal activity (cephalic phase of secretion of insulin, starts before meal ingestion-depends on muscarinic M3 receptors).
Gastrointestinal hormones (gastrointestinal phase of secretion, starts when food enters the stomach and duodenum).
Glucagon (secreted by the a pancreatic cells).
Some amino acids, particularly alanine, glycine, arginine, leucine.
Glucagon-like peptides (GLP): potentiate glucose-induced insulin secretion (but do not stimulate insulin secretion by themselves).
What inhibits insulin secretion?
Sympathetic innervations (a2-adrenoceptor-dependent process, involved in stress response). These receptors induce the hyperpolarisation of the insulin-secreting cells.
Somatostatin (secreted by D pancreatic cells, paracrine modulation). Most of these receptors produce a rise in intracellular calcium leading to the release of insulin.
How does glucose move into muscle cells and adipose tissue?
The process of GLUT4 translocation involves the movement to the cell surface of vesicles containing the glucose transport protein, GLUT4, responsible for bringing sugar into the cell.
Insulin receptor substrates form complexes with docking proteins, and promote GlUT4 translocation.
Exercise stimulates glucose transport by pathways that are independent of IRS.
Not all tissues are dependent on insulin for glucose entry (brain, liver, kidney…) when insulin receptor is no more activated, glucose transporter is internalised back in intracellular vesicles.
What does insulin do to glucose in the liver?
Insulin stimulates glycogen synthesis (glycogenesis).
Inhibits synthesis of new glucose (inhibits gluconeogenesis).
Stimulates glycolysis (for the synthesis of fatty acids).
Resulting effect: prevents glucose output from the liver.
Suppresses lipolysis and favours synthesis of fatty acid and cholesterol.
What does insulin do to glucose in the muscles?
Stimulates glucose uptake (translocation of GLUT-4).
Stimulates amino acid uptake and protein synthesis.
Glucose will be used for glycolysis and synthesis of muscle glycogen.
Resulting effect: promotes ATP production and fuel storage.
What does insulin do to glucose in adipose tissue?
Stimulates glucose uptake (translocation of GLUT-4), and is converted into glycerol-phosphate.
Promotes triglyceride storage.
Inhibits release of fatty acids and stimulates lipogenesis.
Activates adipose tissue lipoprotein lipase (hydrolyse triglycerides in chilomicrons and VLDL).
Stimulate fatty acid transport (translocation of FATP fatty acid transport protein).
Resulting effect: promotes deposition of circulating fat.
In summary:
Insulin exerts its effect by inducing Lipoprotein lipase (LPL) so that circulating triglycerides are hydrolyzed and free fatty acids can enter the adipocyte (through the FATP –fatty acid transport protein- which is also insulin-induced).
Inside the adipocyte, they will reform triglycerides (re-esterification).
Insulin is also required for the transport of glucose, which is needed for re-esterification of the triglycerides once inside the adipocyte (converted into glycerol phosphate).
What effects does insulin have on protein metabolism?
Promotes amino acid uptake and protein synthesis in a number of tissues (muscle).
Decreases protein catabolism in the liver.
What is gluconeogenesis?
Synthesis of new glucose (induced by adrenaline and glucagon, cortisol).
What is glycolysis?
Degradation of glucose into small products (induced by insulin) for ATP or fatty acid synthesis.
What is glycogenolysis?
Degradation of glycogen into glucose (glucagon, adrenaline).
What is glycogenesis?
Synthesis of glycogen from glucose (insulin, cortisol).
What is lipolysis?
Degradation of fatty acid (inhibited by insulin).
What is lipogenesis?
Synthesis of fatty acid and triglyceride (insulin)
What is somatostatin?
It is a pancreatic hormone that is synthesised by the D cells.
5 different somatostatin receptors, all are inhibitory receptors (inhibit cAMP production and hyperpolarise target cells).
Act primarily in a paracrine manner (1/2 life 3 min) to inhibit the secretion of both insulin and glucagon.
On the digestive system:
Decreases rate of nutrient absorption.
Inhibits GI hormones secretion (will reduce exocrine pancreatic secretion).
Suppresses gastric secretion.
Lowers the rate of gastric emptying, and reduces intestine contraction.
