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37 Cards in this Set

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Glucose homeostastis is determined by the balance of -_____ & _____
insulin secretion
insulin sensitivity
Blood glucose levels
fasting - rarely below 72%
eating- rarely above 140-150 %
increase in glucose results in
increase in insuln and decrease in glucagon
cells that are obligate glycolyzers...
they use glucose almost exclusively as their fuel source
RBCs and hypothalamic neurons
starvation diabetes
B cell function is affected and plasma glucose levels change
too much glucose =
waste of important fuels
glycosylation of protiens
glucose toxicity
Long term complications of unregulated glucose are
hyperglycemia
microvascular - retinopathy, neuropathy, anc nephropathy
macrovascular- atherosclerosis
multiple fates of ingested glucose
glycolysis
pentose cycle
glycogen storage
proteins can can be utlized as fuels
6kg of about 24,000 calories
triglycerides
glucose stored with excess intake
most important fuel in adipose tissues
15-20 kg (20-25% of body weight)
enough calories to survive 5-60 days
150,000 calories
horomones regulate glucose homeostasis
glucocorticoids
glucagon
catecholamines
growth hormone
An excess of hormones can result in
diabetes
for example, peo, acromegaly, and Cushings
diabetes by excess hormones is called
counterregulatory hormones
the only established glucose lowering hormone is
insulin
Islets of Langerhans
pancreas 90 %
1 million
major barrier to transplant
What is the relationship between proinsulin, insulin, and c peptide?
for every one insulin molecule secreted on C peptide molecule secreted as well
C peptide is thus a surrogate marker for insulin secretion
fuels
calorigenic substrates
glucose
amino acids
Insulin secretion
exerts a number of important effects of liver, muscles, and adiposes
supresses HGP and influences other cells as well
anabolic
Insulin
mediates its effects via the insulin receptors
composed of alpha and beta chains
becomes phosphorylated during activation and a cascade of events follows
receptor cycling
receptor numbers are regulated by the hormone for the receptor
too much insulin and insulin receptors down regulate- this is a part of insulin resistance
pshosphatidylinositol 3 kinase
important mediator of insulin action
ph inositol containing phospholipids in cell membrane
increase pip3 content
activated by insulin in vivo and in vitro
activation reduced in obesity and type ii NIDM
insulin resitance correlates with a decrease in p13 kinase activation
inhibited by owrtmannin
glucose transport regulated by
p13K
Ketone Bodies
rise in ketones plays a key role in reducing glucose utlization, glucose production, and proteilysis while maintaining cerebral fuel utilization
Obesity
assessed by BMI and waist to hip ratio
BMI of 25 and above 25-30 overwt
30-40 obese
waist to hip ratio is < than .72
what causes obesity?
leptin deficient = morbidly obese
hypothalmic lesions = obese
leptin
deficiency = obesity
plays an important role in fertility- it regulates teh hypothalamic/pituitary/ and gonadal axis
hyperinsulinemia
contributes to fat accretion and the storage of calories
chronic hyperinsulinemia has adverse effects: insulin resistance, atherogenesis, and syndrome X and metabolic syndrome
Starvation
biochemical event associated with ketogenesis, glucogenesis, lipolysis, glycogenolysis, all set inot motion by a fall in one hormone
obesity
hyperinsulinemia associated with obesity causing insulin resistance, which in turn requires the Beta cell to work harder, a vicious cycle... If the Beta cell fails or decompensates then diabetes results.
type I diabetes
autoimmune... target antigens include proinsulin, insulin, GAD. other antigens
prodromal period of IDDM
first phase loss of insulin secretion
the destruction of most beta cells has already occurred
antihyperglycemic treatment strategies for type II
diet and exercise
sulfonlureras
non-SU secretagogues
insulin
exenatide
biguanides
alpha glucosidase inhibitor
thiazolidinedions
biguanides
metaformin
decreases heptic glucose production
alpha glucosidease inhibitor
decrease carboyhydrate absorption
thiazolidinediones
decrease insulin resistance
exantide
increase glucagon, satiety
decrease gastric dumping
diabetes and pregnancy
dramatic increase in insulin requirements occur
PRL or placental lactogen responsible fo augmenting beta cell secretion