Lecture 10- Dysregulation of Glucose and Fat Metabolism Flashcards
what is the genetic predisposition of type 1 diabetes compared with type 2
type 1 = moderate
type 2 = very strong
what is the frequency of ketosis in type 1 and type 2 diabetes
type 1 = common
type 2 = rare
what is the problem in type 1 diabetes
B cells are destroyed, eliminating production of insulin
what is the problem in type 2 diabetes
insulin resistance combined with inability of B cells to produce appropriate quantities of insulin
what is the fasting + random glucose level that is a symptom of diabetes
fasting glucose > 7mmol/L or random >11.1 mmol/L
what level of HbA1c be a symptom of diabetes and why
HbA1c > 50 mmol/mol
higher levels than this would suggest that you have had elevated glucose levels for sometime
what are some symptoms of diabetes
thirst
frequent urination
fatigue
hyperventilation
blurred vision
coma
what are glycosuria, osmotic diuresis and dehydration common symptoms of
diabetes
what are the three stages that lead to the development of diabetes from obesity
obesity
insulin resistance
glucose intolerance
metabolic syndrome
type 2 diabetes
what can not be distinguished between a normal and obese pre diabetic
can not distinguish between the obese and normal patient from glucose levels in the blood
what do insulin resistant obese people require more of
require more insulin to get the same glucose control as a normal person
= this is what you can the difference btwn normal and obese on graph
over time what happens to a insulin resistant diabetic over time in the control of blood glucose
over time, lose the control of blood glucose as their levels are constantly high and never properly go back down before the next meal
what does insulin resistance mean
reduced response to the same amount of insulin
what does hyperinsulinaemia diminish
the ability of b cells to respond to further increase in blood glucose
during insulin resistance, what happens to the processes that are normally stimulated by insulin
they arent stimulated
during insulin resistance, what happens to the processes that are normally inhibited by insulin
they aren’t inhibited
what are things that are normally stimulated which aren’t during insulin resistance (what happens to them)
glucose uptake
glycolysis
fatty acid uptake
are decreased
what are things that are normally inhibited which aren’t during insulin resistance (what happens to them)
gluconeogenesis
lipolysis
fatty acid oxidation
ketogenesis
are increased
what are the two theories about how insulin resistance develops and what is there evidence that they both do
oxidative stress
inflammation
evidence that they both alter the insulin signalling pathway
how does oxidative stress lead to insulin resistance
overweight people often have a high flux of glucose and lipid into the mitochondria
high activity of the electron transport chain can cause oxidative stress
this can cause miss phosphorylation of parts of the insulin signalling pathway
how does inflammation lead to insulin resistance
pro-inflammatory cytokines can activate serine/threonine kinases, which can interrupt the normal pathway of insulin signalling
are all tissues and pathways affected equally by insulin resistance
no
diabetics can develop fatty livers which can lead to what and what does this tell us about triglyceride synthesis
can lead to cirrhosis
this tells us triglyceride synthesis is still going on in the liver
in insulin resistant states what happens to the mobilisation of fats and therefore what is there more of in the liver and more of what will be produced
greater mobilisation of fats, therefore more TAG in the liver due to increased mobilisation of fats
more VLDL is produced to try export the extra fat from the liver
in insulin resistant states LDL is not being hydrolysed so more what is released from the liver
more VLDL is released from the liver
in insulin resistant states lipoprotein lipase is not stimulated, what does this mean
there is more chylomicron and remnant fatty acid into the liver
insulin stimulates lipogensis, what happens in insulin resistant states and what does it lead to
this pathway is not effected, this leads to fatty liver as other pathways are inhibited but this isnt
what happens in adipose tissue in insulin resistant states
increased delivery of fatty acids to liver via increased lipolysis due to increased HSL activity in adipose
what happens in adipose and muscle tissue in insulin resistant states
VLDL remnant particles have increased triglyceride content due to reduction in LpL activity = increased blood TAGs
treatment of type 2 diabetes
lifestyle changes
drugs = e.g metformin
how does endurance training enhance your glucose tolerance
exercise will increase your insulin sensitivity
what does the drug Metformin inhibit and what does this slow
mitochondrial electron complex 1, slows ETC and reduces ATP production
as Metformin reduces ATP production what will increase
AMP will increase
what will increased AMP levels increase and what will that activate
increased AMP will increase AMPK, which will activate transcription factors that will impact proteins in the gluconeogenesis pathway
what will increased AMPK down regulate
mGPD enzyme (glycogen phosphate dehydrogenase)
what will decreased mGPD do
increase NADH, meaning more lactate will be formed
