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 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 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
