Insulin Secretion and Intermediary Metabolism Flashcards
State four hormones that increase blood glucose concentration.
Glucagon Cortisol Catecholamines Somatotrophin
State some complications of diabetes.
Diabetic retinopathy Diabetic ketoacidosis Peripheral neuropathy Coma Heart Attacks Stroke
What is the normal blood glucose range?
4.0-5.5 Mm
What percentage of pancreatic cells are islets of Langerhans?
2%
What do the delta cells in the islets of Langerhans produce?
Somatostatin
Why do cells in the islets of Langerhans have gap junctions?
Allow hormones to have a paracrine effect
What effect does somatostatin have on glucagon and insulin secretion?
Decreases both insulin and glucagon secretion (it is sometimes called ‘endocrine cyanide’)
What are the main effects of insulin?
Increase glycogenesis Increase glycolysis Increase glucose transport via GLUT-4 Decrease lipolysis Increased protein synthesis ( and AA transport) Overall decrease blood glucose
State some factors that increase and decrease insulin secretion.
Increase: Certain amino acids Gastrointestinal hormones Parasympathetic activity Decrease: Sympathetic activity Somatostatin
What is the effect of GLP-1?
Amplifies our insulin response - it makes us produce more insulin
What are the main effects of glucagon?
Increased lipolysis Increased AA transport x Increased hepatic gluconeogenesis Increase blood glucose INSULIN inhibits glucagon release (via paracrine)
What is the role of glucokinase?
It is the rate limiting step that regulates insulin secretion It converts glucose to G6P Glucose moves into the beta cell via Glut-2 (which is NOT insulin regulated) It is then converted to G6P by glucokinase (hexokinase IV), which then determines insulin secretion
Describe the structure of insulin and what can be measured to indirectly give an indication of blood insulin concentration?
Insulin is synthesised as a prohormone with an A, B and C chains The C chain is removed in the conversion of proinsulin to insulin so the ratio of insulin: C peptide is 1:1 This means that C peptide can be measured to give an indication of insulin output
Describe how glucose uptake causes release of insulin from the beta cell.
Glucose enters through Glut-2 and is metabolised to produce ATP There is an increase in intracellular ATP concentration This BLOCKS ATP sensitive potassium channels —> changes membrane potential Leads to opening of voltage dependent Ca2+ channels Ca2+ influx causes insulin exocytosis
What is the incretin effect?
Oral glucose load stimulates more insulin release than IV glucose load This is to do with intestinal hormones
What enzyme breaks down GLP-1?
Dipeptidyl Peptidase-4 (DPPG-4)
Describe the differences in first phase insulin release between a normal person and someone with T2DM.
Administration of glucose causes a sharp increase in insulin in a normal person This surge of insulin (first phase release) is not present in someone with T2DM
Describe the structure of the insulin receptor and how it works.
Insulin is a peptide hormone so it doesn’t enter the cell The receptor has two alpha subunits and two transmembrane beta subunits, which have tyrosine kinase domains Insulin binds to the alpha subunits and cause a conformational change in the beta subunits You get phosphorylation of the receptors which recruit other substances that also get phosphorylated and have effects on the metabolic pathway
Where does the fault causing insulin resistance lie?
Insulin resistance lies in the post-receptor cytoplasmic elements of insulin function
How low would blood glucose need to be to lead to a coma, death and unconsciousness?
2mM
What proportion of the pancreas is associated with exocrine secretion?
98%
What’s the role of tight junctions in the islet of langerhans?
Form small intracellular spaces. Small collections of fluid between cells are formed by tight junctions.
Why is it important that some gastrointestinal hormones increase insulin secretion?
before food we eat effects blood glucose, the food in our gut is making us produce insulin
Wheres the main effects of glucagon?
liver - hepatocytes
What is pre-proinsulin?
proinsulin plus a signal sequence
Whats the other role of the insulin receptor?
growth (mitogenic pathway)
Why is First Phase Insulin Release (FPIR) important?
Switches off hepatic gluconeogenesis
