4 - Insulin Secretion Flashcards
What is the structure of insulin and what can be measured to indirectly give an indication of blood insulin concentration?
- synthesised as prohormone with A, B and C chains
- C chain removed in conversion of proinsulin to insulin
- ratio of insulin: C peptide is 1:1
- C peptide measured to give indication of insulin output
What is the incretin effect?
- oral glucose load stimulates more insulin release than IV glucose load
- to do with intestinal hormones
What hormone decreases blood glucose?
insulin
What hormones increases blood glucose?
- glucagon
- catecholamines
- somatotrophin
- cortisol
What are the 3 cell types in pancreatic islets of Langerhans and what do they secrete?
- α cells: glucagon
- β cells: insulin
- δ cells: somatostatin
What does somatostatin do?
decreases production of insulin and glucagon
What are some features of the islets of langerhans?
- small clumps of cells
- 2% of cells in pancreas (not associated with exocrine secretions via duct into small intestine)
- gap junctions between cells allow small molecules to pass directly between cells (paracrine effect)
- tight junctions form intercellular spaces (collections of fluid between cells)
What factors increase insulin secretion?
- increased blood glucose
- glucagon
- parasympathetic activity (β receptors)
- some GI hormones
- glucagon like peptide
- certain amino acids
What factors decrease insulin secretion?
- somatostatin
- sympathetic activity (α receptors)
What can the brain use as an energy supply?
- ketones
- glucose
- NOT fatty acids
What are the physiological actions of insulin?
- decreases blood glucose conc. (increases glycogenesis, glycolysis and glucose transport into cell using GLUT-4)
- prevents breakdown of protein
- stops lipolysis
- increases lipogenesis
What factors increase glucagon secretion?
- decreased blood glucose
- certain amino acids
- certain GI hormones
- parasympathetic activity
- sympathetic activity
What factors decrease glucagon secretion?
- insulin
- somatostatin
What are the physiological actions of glucagon?
- increases hepatic glycogenolysis (increasing blood glucose)
- increases lipolysis, increasing gluconeogenesis (increasing blood glucose)
- increases amino acid transport to liver, increasing gluconeogenesis (increasing blood glucose)
How is insulin secreted?
- glucokinase is rate determining step regulating secretion
- glucose enters cell through GLUT-2 (not insulin regulated)
- glucose converted to glucose-6-phosphate by glucokinase (important for sensing glucose conc. by β cell)
- ATP produced blocks ATP sensitive potassium channels
- VGCC open, allowing calcium to rush in and insulin to be secreted
What are the 2 types of diabetes mellitus and what are their defining features?
- type 1: elevated glucose where insulin is required to prevent ketoacidosis
- type 2: defined in terms of glucose but related to hypertension and dislipidaemia
What is glucagon like peptide 1 (GLP-1) and its features?
- gut hormone secreted in response to nutrients in gut
- transcription product of proglucagon gene (most from L cells)
- stimulates insulin and suppresses glucagon
- increases satiety
- short half-life due to rapid degradation from dipeptidyl peptidase 4 (DPPG-4)
What are DPPG-4 inhibitors used for?
to treat type 2 diabetes mellitus
What is the insulin receptor?
- protein/polypeptide hormone that doesn’t cross membranes
- α subunit recognises 3D shape of insulin and causes conformational change in β subunits which cross membranes
- phosphorylation of β subunits important in recruiting substrates that go on to have effects on metabolic pathway
- provides metabolic effect on glucose, amino acids and fatty acids and affects growth
What does and doesn’t cause insulin resistance?
- not caused by receptor not being able to recognise insulin or due to transmembrane portion of receptor not working
- lies in post-receptor cytoplasmic elements of insulin function
