Diabetes Flashcards
Describe the features of the Islets of Langerhans.
- endocrine
- alpha-cells produce glucagon
- beta-cells produce insulin
- delta-cells produce somatostatin
- F-cells produce pancreatic polypeptide
- ghrelin
What is the origin of the pancreas?
Outgrowth of foregut (endodermal origin)
What do the exocrine glands of the pancreas produce?
Digestive enzymes e.g. pancreatic lipase, pancreatic amylase, trypsinogen
Outline the production of insulin from beta-cells.
removal of signal peptide (ER)
Insulin mRNA —> Preproinsulin ————————> Proinsulin
Endopeptidases
——————-> Mature insulin + C-peptide —> Packaged in Golgi into secretory granules which accumulates in cytoplasm
What is special about the bonding in an insulin molecule?
3 disulfide bonds
1 intra-chain
2 inter-chain (which are broken)
Outline the release of insulin from beta-cells.
Facilitated diffusion of glucose through GLUT2 channel
Glucokinase phosphorylates glucose (prevents diffusion out of cell)
Glucose-6-P used in glycolysis to produce ATP
ATP closes the ATP-sensitive K+ channel
K+ causes depolarisation of inside of cell
Opens voltage-gated Ca2+ channel
Entry of Ca2+ causes exocytosis of vesicles containing insulin
Outline the action of insulin on cells.
Insulin binds to alpha-subunit of insulin receptor, causing beta-subunit to activate tyrosine kinase
Gene expression affected and signal transduction (stimulated insertion of GLUT4 + lipogenesis + protein synthesis)
Insertion of GLUT4 channel - glucose enters cell (glucose utilisation + glycogen synthesis stimulated)
What is margination?
Movement of storage vesicles to cell surface
What is the model of insulin secretion?
Biphasic release
What is the key difference in structure between insulin and glucagon?
Glucagon has no disulfide bridges (therefore is more flexible and synthesis is more simple)
What is the definition of diabetes mellitus?
State of hyperglycaemia leading to small and large vessel damage in which there is premature death from CAD
Why does hyperglycaemia cause damage to blood vessels?
NADPH depleted as glucose is converted to sorbitol by aldose reductase
Sorbitol accumulation = osmotic damage
Disulfide bridges formed
Why does diabetes cause vascular changes?
Glycosylation of proteins in vessel walls, leading to arteriosclerosis (hardening of vessel walls)
