Harvluck B8 W4 Flashcards
Insulin effect
K+ accumulation and lipolysis which reduces availability of ketones for ketogenesis and ketoacidosis in skeletal muscle
Ketoacidosis
High levels of ketone bodies. Causes vasodilation which results in hypotension and hypothermia caused by insulin deficency
Incretin which reduces glucagon
Gastric Insulinotropic peptide (GIP) produced by Intestinal K cells. High levels of this in obesity
Diabetes insipidus
ADH deficiency due to neurological or nephrogenic dysfunction
GLUT2 transporter
Protein on beta cells that causes rise in glucose
GLUT4 transporter
Protein on skeletal, adipose or vascular cells that takes up glucose.
Insulin receptor substrate 1
Phosphorylation triggers translocation of GLUT-4 to membrane for glucose uptake
Action of secretin
Produced by S cells of the duodenum. Secretin acts to cause conversion of ATP -> cAMP. This results in K+ channel and cAMP activated Cl- channel (CFTR) activation. There is great Cl- efflux which is recycled by the CL-/HC03- exchanger to cause bicarbonate secreiton of HCO3-.
LADA
Absence of ketoacidosis.
Inactive storage form of insulin
Hexameric insulin
Difference between insulin intravenous vs orally
Incretin effect is increased insulin production higher in oral than IV.
Type 1 diabetes genetic association
Mutation in immunoregulatory genes and MHC
Active form of insulin
Monomeric insulin
What triggers type 1 diabetes?
Childhood enterovirus that cause bystander activation and molecular mimicry
What gives free-flow for bicarbonates?
Water- a lack of this in cystic fibrosis causes autodigestion
Effect of GLP-1
Enhances insulin secretion. Increase pancreatic delta cell release of somatostatin, increases Na+ excretion from kidney and reduces inflammation. Cardioprotective due to reduced fatty acid metabolism.
Cause of neonatal diabetes
Genetic mutation in insulin production
Metformin mechanism of action
cAMP
Slow GLP-1 analogue
Liraglutide
What causes production of gut hormones?
Food being ingested and moving through GI tract
Macrovascular complications of diabetes
Kidney disease, hypertension and atherosclerosis of major arteries of the heart
Effect of insulin on receptors
Phosphorylation on G protein coupled receptor
Adverse effect of SGTL2 inhibiotr
Increased genitourinary infection
Cytokines chronically activated in type 2 diabetes
TNF alpha and IL-6- this is due to ceramide which causes insulin resistance
Cells that produce ghrelin
Stomach and pancreatic epsilon cells
Golgi body
Organelle where proinsulinn matures into active insulin via action of endopeptidases
Formation of glucagon
Action of proprotein convertase cleaving proglucagon in alpha cells
Thiazolidinediones
PPAR gamma agonist
What causes insulin release exocytosis?
Metabolic and vagal nerve stimualtion
Role of bicarbonate
Reduce acidity of chyme in duodenum
Long-acting GLP-1 analogue
Exenatide
Effect of somatostatin
Neuropeptide and gastirc peptide produced after eating. Inhibits glucagon and insulin release and exocrine pancreatic functions
Main killer of beta cells
CD8+
Free fatty acids
Cause fat oxidation in mitochondria that produes reactive oxygen species which cause oxidative stress. Produces ceramides for kinase PKB/ Akt which reduces GLUT4 movement to membrane and glycogen synthesis.
Condition associated with Type 1 diabetes
Diabetic nephropathy where high glucose causes glomerulus malfunction and leakage of protein that cause scar tissue and cause kidney failure. Occurs in type 2.
Glucose entry
Increases intracellular ATP for depolarisation which opens Ca2+ channels and causes insulin exocytosis
What is Phase 1?
Beta cells that die by natural causes or infection undergo apoptosis and removed by macorphages. Instead, natural dendritic cells enter and activate to take them up and present to B and T cells.
Phase 2
Priming of auto-reactive B and T cells with a balance between regulation and activation. The cells move from pancreatic lymph node into the pancreatic islets.
Pancreatic cells secreting somatostatin
Delta cells
Effects of severe insulin deficiency
Increased growth hormone levels, cortisol levels and increased glucagon levels
Osmotic diuresis
Increased urination which increases loss of sodium
