type 2 diabetes Flashcards
what does insulin promote in cells
gene expression, dna replication, glycogen sythesis, glucose uptake in muscle and liver, fatty acid synthesis, protein sythesis
what does insulin reduce in cells
glycogenolysis in liver and muscle, lipolysis in adipose, cell apoptosis, (gene expression?)
describe insulin mechanism of action in cell
insuling binds to receptor, the receptor is autophosphorylated, ir catalyses tyrosine phosphorylation of insulin receptor substrates, irs1 activates several signalling pathways
the PI(3)K (phosphatidyl inositol 3 OH kinase) pathway is involved in??
protein
carbohydrate and fat metabolism
• the MAP (mitogen activated protein)
kinase pathway is involved in?
cell growth
and differentiation through ras.
RS-1 binding and phosphorylation and
subsequent activation of PI3-K lead to
increase in glut4 oninsulin sensitive tissue, glut 4 transported via vesicles to surface
what is ras
ras is an oncogene product, a small GTPase
• it is a signal transduction protein
• it activates a number of pathways
• MAP kinase pathways particularly important
how does insulin alter dna expression
shc docking protein phosphorylates ras which activates raf, a cascade follows resulting in MAPK protein phosphorylation activating transcription factor affecting gene expression
how does Termination of insulin signal occur
protein phosphatases and phosphoinostide phosphatases inhibit at several points along the signalling pathway, phosphorylation of irs on serine/threonine sites is another turn off mechanism, these mechanisms are important in insulin resistance
defien insulin resistance
Condition in which normal amounts of insulin are inadequate to maintain normal concentrations of blood glucose • both insulin and glucose are high • often associated with obesity
what is the simplest explanation of insulin resistance
high conc of circulating insulin causes insulin receptors to be down regulated, interference with insulin signalling pathway and inflammation contribute to resistance
why are obese people at risk of diabetes
more adipose tissue and adipose tissue plays a significant role
what is the role of adipose tissue
produces metabolites, hormones, cytokines which modulate metabolism,
Characteristics of the obese state which are key in
development of insulin resistance
Chronic inflammation
• Oxidative stress
• Hyperinsulinaemia
• Lipotoxicity
the chracteristics of the obese state intefere with what mechanisms to do with insulin control
insulin secretion, insulin signalling pathways, glucose transport, insulin receptor numbers and binding affinity
leptin is produced in adipocytes what does it do for insulin
leptin is good it increase sensitivity however , obese are often leptin resistant
what does adiponectin do
it increases insulin sensitivity however decreased in obese
why are DAG and FFA from aipose tissue bad
FFA and DAG can impair insulin sensitivity by interfering with IRS activation
TNFα effects IRS positively or negatively
TNFα also interferes with IRS activation which will inhibit insulin signal BAD
how does inflammation effect insulin pathways and metabolism
Adipose expansion in obesity recruits monocytes which become
macrophages
• They secrete proinflammatory cytokines e.g. TNFα and IL-6
• They lead to increased secretion of FFA and ceramide
• and decreased secretion of adiponectin
how does tnfa work
TNFα causes Ser phosphorylation through JNK kinase which
terminates insulin signal prematurely
explain role of oxidative stress in obese individual effecting inuslin pathways
In obesity the oversupply of fatty acids and
glucose to the mitochondria leads to ROS
overproduction
• They interfere with PI3K activity.
explain role of lipotoxicity in IR
increase of tag ffa ceramide in obese, intefere with phosphorylation of IRS causing premature sig termination causing IR. Thiazolidinediones inhibit lipolysis and can help to some extent
does type 2 diabetes cause metabolic syndrome
I may not be completely right with this flashcard
no
Type 2 diabetes is considered a complication of
metabolic syndrome.
•
• In a patient with impaired glucose tolerance or
impaired fasting glucose who also has the
characteristics of metabolic syndrome the risk of
developing type 2 diabetes is twice as high
what is metabolic syndrome
abdominal waist circumference that is large, high BP, high blood glucose, high serum TAG, low hdl conc
