12: Endocrine Pancreas Flashcards
Three types of innervation to the endocrine pancreas
Adrengergic, cholinergic, peptidergic
Three ways cells in the islets communicate
- Ion concentrations
- Gap junctions between a’s and B’s
- Blood supply
How does blood flow through the islets
Center receives blood first -> insulin released into blood flows by a and D cells so they can sense how much insulin is in blood
C peptide secretion and function
Secreted equally with insulin - used as an endogenous insulin secretion marker
Biphasic release of insulin
initial spike within minutes + further increase half hour to an hour later
Exercise on blood sugar
Muscle contraction activates AMPK -> causes GLUT4 translocation so more glucose can enter cells
Insulin actions on skeletal muscle
Increases: glucose uptake, glycogen synthesis, glycolysis, protein synthesis
Decreases: protein breakdown
Insulin actions on liver cells
Increases: glycogen synthesis, glycolysis, hexose monophosphate shunt, pyruvate oxidation, lipid storage, protein synthesis
Decreases: gluconeogenesis, lipid oxidation, protein breakdown
Insulin actions on adipose cells
Increases: glucose uptake, glycolysis, uptake of FAs
Decreases: lipolysis
Insulin major effect on cells in general
Increase K uptake -> decreases K in ECM
What three metabolic processes does glucagon increase
Gluconeogenesis, lipolysis, glycogenolysis
Glucagon and insulin actions on one another
Glucagon inhibted by insulin, but glucagon stimulates insulin release
How many cases of DM2 have insulin resistance?
95%
Incretin effect
normal spike of insulin in healthy patients due to GI hormone release - over time, pts with insulin resistance lose normal incretin effect
Environmental risks for DM 2
caloric excess, sedentary, maternal disease and nutrition, rapid post-natal growth, sleep debt, endocrine disrupters, chronic inflammation
What happens when adipose tissue is inflamed in terms of insulin resistance?
Recruits M1 macrophages -> release of inflammatory markers (IL-6, TNFa, IFN-y) -> disruption of adipokines + release of FA’s
Three types of medications for DM2 treatment
- Insulin sensitizers
- Sulfonylurea receptors
- Insulin secretagogues
Two types of insulin sensitizers
Biguanide drugs (metformin), TZDs
What are sulfonylurea receptors associated with?
ATP-dependent K channels
What causes DM 1?
T cell mediated destruction of B cells of pancreas -> inadequate insulin secretion
When do sx start to appear with DM 1?
When about 80% of B cells are destroyed
What causes DKA?
Decreased utilization of ketoacids
Three major symptoms that occ with DM 1
Hyperkalemia, osmotic diuresis, glucosuria
What causes hyperkalemia in DM 1?
Lack of insulin effect on Na/K ATPase
What causes osmotic diuresis and glucosuria in DM 1?
Increased blood glucose increases filtered load of glucose, exceed reabsorption capacity of proximal tubule + water and electrolyte reabsorption is blunted
What does polyuria cause in DM 1?
Increased excretion of Na and K even though urine concentration of electrolytes is relatively low
Two major alleles associated with DM 1
HLA DQ2 and DQ8
Environmental factors with DM 1
early exposure to cows milk, vitamin D deficiency, gluten intolerance, childhood infections, obesity
Treatment for DM 1
Timing insulin doses to meal consumption to mimic physiological response
