Pancreas and Diabetes Flashcards
What are the three domains of an insulin receptor?
- insulin binding domain
- transmembrane domain
- tyrosine kinase domain
What is the function of the insulin binding domain?
- extracellular, binds insulin
- regulates kinase domain (keeps inactive until insulin binds)
What is the function of the transmembrane domain?
- holds receptor in place and transmits conformation signal when insulin is bound (alpha helix change)
What is the function of the tyrosine kinase domain?
- intracellular
- autophosphorylates across to neighbour kinase domain plus recruits and phosphorylates substrates like insulin receptor substrate to start phosphorylation cascade
How does the kinase stay inactive until insulin is bound?
- alpha subunit structurally constrains beta subunit
What is leprachaunism?
- defecive IR
- some mutations lead to less severe phenotype: insulin resistance
- heterozygous less severe
- elf-like features
Why would a heterozygous condition result in less severe leprechaunism?
- recessive disorder
- both alleles must carry mutation
What are the differences in symptoms of type I and type II diabetes?
- type I: weight loss, serious/never asymptomatic
- type II: obesity, asymptomatic
What causes type I diabetes?
- no insulin producing B cells
- most commonly caused by autoimmune disease that specfically destroys B cells in the pancreas
- genetics may contribute
How is type I diabetes treated? What results if not treated?
- with insulin, diet and lifestyle
- hyperglycemia and eventually coma
- no cure
What is type I diabetes?
- juvenile diabetes or insulin-dependent diabetes
- chronic condition where pancreas produces little or no insulin
When does type I diabetes usually appear?
- during childhood or adolescence
- sometimes adults
What are the three pre-requisites for development of type I diabetes?
- B cell-reactive T cells need to be activated
- response needs to be proinflammatory
- immune regulation of autoreactive responses must fail
What is type II diabetes?
- insulin present but target cell is resistant
- reduced insulin synthesis and insulin signaling
What are the 5 reasons a target cell is resistant in type II diabetes?
- receptor insensitive or downregulated by hyperinsulinism
- receptor defective
- Ab against receptor blocks insulin
- signal pathway defective
- poor response of target organ due to obesity, liver disease, muscle inactivity
How is type II diabetes treated?
- drugs that lower glucose production in liver and improve sensitivity to insulin
- drugs that stimulate insulin secretion (may cause hypoglycemia)
- drugs that affect the glucose absorption in the intestine
- diet and exercise mainly
- reduce stress, increase quality of sleep
What does an islet cell look like in someone with type II diabetes?
- B cells decrease
- replaced by amyloid deposits
- reduction in ratio of B cells to alpha cells (produce glucagon)
How do drugs that affect the glucose absorption in the intestine work?
- use incretin GLP-I o increase insulin and decrease glucagon
- slow gastric emptying that can be helpful in controlling glucose levels
- homologous to GLP-I but lasts longer and acts as GLP-I agonist
What is lipogenesis?
- store fat
- happens when we eat sugar
What kind of diet impairs sugar tolerance? How does this relate to insulin resistance?
- low carb and high fat diet
- we can decrease insulin resistance by decreasing fat intake
What is hypoglycemia and what causes it?
- occurs in diabetics when a treatment to lower the elevated blood glucose inaccurately matches the body’s physiological need
- causes glucose to fall to a below-normal level
- causes organ and brain damage without treatment
What are glucose transporters regulated by?
- glucose
What are the three conditions relating to glucose regulation and how does this affect GLUT1?
- hyperglycemic: too much glucose, downreg of GLUT 1
- normal: appropriate amount of glucose, transported across BBB and delivered to neurons
- hypoglycemic: upregulation of GLUT1 with too little glucose
What is hypoglycemic unawareness?
- when become desensitized to hypoglycemia so defenses are down
- insulin, glucagon, epinephrine response attenuated
- brain still gets enough sugar but can’t tell there is a problem
____ ____ steps may be altered in type II diabetes.
insulin signaling
What results from food intake?
- increase insulin
- release GLP-I and GIP from gut
- further increase insulin
- leads to glucose storage
What results from exercise?
- increase glucagon
- need energy so breakdown storage products like carbs
- increase blood glucose
What results from a high amino acid meal in the presence of glucose?
- increase insulin and glucagon
- protect from hypoglycemia (prevent insulin from lowering blood glucose too low)
What results from starvation?
- decrease insulin and decrease glucagon
- system needs to slow down and preserve energy
What steps occur in the body to remove the glucose from our blood after a meal?
- insulin inhibits glucagon
- GLP-I releases at same time as insulin and increases insulin production
- GLP-I slows gut emptying and increases absorption (inhibits food intake)
- many other factors and complex interactions
How is insulin removed from circulation?
- degraded by insulinases within a few minutes
- receptors internalize
