Diabetes Path Flashcards
diabetes is the ________ leading cause of death
seventh
prevalence of diabetes in ethnicity
most to least
- American Indian/Alaska Native
- black
- Hispanic
- white
- Asian
risk factors for type 1
genetic predisposition or autoimmune trigger
risk factors for type 2
family history, overweight/obesity, sedentary lifestyle, race/ethnicity, American, previous pre-diabetes, gestational diabetes or baby <9lbs, hypertension, decreased HDL, increased TG, PCOS, vascular disease
parts of proinsulin
A chain, B chain, C-peptide
what creates active insulin
C-peptide cleavage
C-peptide and insulin are
stored and co-secreted from secretory granules
beta cells secrete
islet amyloid polypeptide (IAPP) or amylin
amylin
further helps insulin release
beta cell - fasting
cell membrane remains mostly polarized allowing very little calcium influx, incretin hormone levels are low
fasting insulin
small basal amount of insulin is released to maintain euglycemia and glucose supply to muscle, fat, and liver
is there always insulin being released?
yes, unless your beta cells don’t work
fasting glucose is at it’s highest or lowest level?
lowest
beta cell - fed
extracellular glucose concentrations increase; incretin hormone levels/binding increase
food intake causes
an increase of glucose concentration
glucose is transported into the beta cell by
GLUT2 - which is not insulin dependent
glucose under goes glycolysis which yields
pyruvate - pyruvate enters the mitochondria yielding ATP
increase in ATP causes
closure of ATP-dependent K+ channels
K+ channel closure causes
depolarization of the cell
Depolarization allows for
opening of calcium channels and calcium influx occurs
increase intracellular calcium causes
migration of insulin secretory granules to the cell membrane and release of insulin
after insulin is secreted, how much is destroyed by the liver?
half
what happens to the remaining insulin
enters circulation and is able to bind to the receptor
insulin binding to receptor causes a cascade of reactions
1) expression of GLUT4 transporters
2) GLUT4 is expressed on the surface of the cell in response to insulin binding to its receptor
3) this causes the cell to take up glucose
fasting glucose homeostasis
decrease insulin which increases glucagon which increases glucose production which decreases uptake by fat/muscle and increases lipolysis
fed glucose homeostasis
increases insulin which decreases glucagon which decreases glucose production which increases uptake by fat/muscle and increases lipolysis
in glucose homeostasis there is a balance between
hepatic production and peripheral uptake/utilization
overall fasting glucose homeostasis
undergo gluconeogenesis in the liver, undergo lipolysis to help generate more glucose
overall fed glucose homeostasis
decrease glucagon as insulin goes up, stops stimulating liver to produce insulin, and increase uptake of fat
Type 1 DM has
islet cell antibodies and activated lymphocytes in islets/lymph/circ
T cells proliferate when
exposed to islet protein (presence of cytokines in protein)
autoimmune targets
insulin, glutamic acid decarboxylase, Tyr phosphate, phogrin
stages of type 2
normal, insulin resistance (hyperinsulinemia), impaired glucose tolerance (postprandial), type 2 diabetes mellitus (fasting)
role of genetics in type 2
increased risk if present in single parent, genetic risk is polygenic, environment clouds the picture
genetic predisposition of type 2
insulin signaling and obesity/fat distribution
beta cell dysfunction precedes hyperglycemia by
10+ years
primary cause of beta cell dysfunction is
poor metabolic environment
glucotoxicity
oxidative metabolism of glucose leads to production of reactive oxygen species, which are normally quickly detoxified
