Lecture 10- Dysregulation of Glucose and Fat Metabolism

Question 1

what is the genetic predisposition of type 1 diabetes compared with type 2

Answer 1

type 1 = moderate

type 2 = very strong

Question 2

what is the frequency of ketosis in type 1 and type 2 diabetes

Answer 2

type 1 = common

type 2 = rare

Question 3

what is the problem in type 1 diabetes

Answer 3

B cells are destroyed, eliminating production of insulin

Question 4

what is the problem in type 2 diabetes

Answer 4

insulin resistance combined with inability of B cells to produce appropriate quantities of insulin

Question 5

what is the fasting + random glucose level that is a symptom of diabetes

Answer 5

fasting glucose > 7mmol/L or random >11.1 mmol/L

Question 6

what level of HbA1c be a symptom of diabetes and why

Answer 6

HbA1c > 50 mmol/mol

higher levels than this would suggest that you have had elevated glucose levels for sometime

Question 7

what are some symptoms of diabetes

Answer 7

thirst
frequent urination
fatigue
hyperventilation
blurred vision
coma

Question 8

what are glycosuria, osmotic diuresis and dehydration common symptoms of

Answer 8

diabetes

Question 9

what are the three stages that lead to the development of diabetes from obesity

Answer 9

obesity
insulin resistance
glucose intolerance
metabolic syndrome
type 2 diabetes

Question 10

what can not be distinguished between a normal and obese pre diabetic

Answer 10

can not distinguish between the obese and normal patient from glucose levels in the blood

Question 11

what do insulin resistant obese people require more of

Answer 11

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

Question 12

over time what happens to a insulin resistant diabetic over time in the control of blood glucose

Answer 12

over time, lose the control of blood glucose as their levels are constantly high and never properly go back down before the next meal

Question 13

what does insulin resistance mean

Answer 13

reduced response to the same amount of insulin

Question 14

what does hyperinsulinaemia diminish

Answer 14

the ability of b cells to respond to further increase in blood glucose

Question 15

during insulin resistance, what happens to the processes that are normally stimulated by insulin

Answer 15

they arent stimulated

Question 16

during insulin resistance, what happens to the processes that are normally inhibited by insulin

Answer 16

they aren’t inhibited

Question 17

what are things that are normally stimulated which aren’t during insulin resistance (what happens to them)

Answer 17

glucose uptake
glycolysis
fatty acid uptake

are decreased

Question 18

what are things that are normally inhibited which aren’t during insulin resistance (what happens to them)

Answer 18

gluconeogenesis
lipolysis
fatty acid oxidation
ketogenesis

are increased

Question 19

what are the two theories about how insulin resistance develops and what is there evidence that they both do

Answer 19

oxidative stress
inflammation

evidence that they both alter the insulin signalling pathway

Question 20

how does oxidative stress lead to insulin resistance

Answer 20

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

Question 21

how does inflammation lead to insulin resistance

Answer 21

pro-inflammatory cytokines can activate serine/threonine kinases, which can interrupt the normal pathway of insulin signalling

Question 22

are all tissues and pathways affected equally by insulin resistance

Answer 22

no

Question 23

diabetics can develop fatty livers which can lead to what and what does this tell us about triglyceride synthesis

Answer 23

can lead to cirrhosis

this tells us triglyceride synthesis is still going on in the liver

Question 24

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

Answer 24

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

Question 25

in insulin resistant states LDL is not being hydrolysed so more what is released from the liver

Answer 25

more VLDL is released from the liver

Question 26

in insulin resistant states lipoprotein lipase is not stimulated, what does this mean

Answer 26

there is more chylomicron and remnant fatty acid into the liver

Question 27

insulin stimulates lipogensis, what happens in insulin resistant states and what does it lead to

Answer 27

this pathway is not effected, this leads to fatty liver as other pathways are inhibited but this isnt

Question 28

what happens in adipose tissue in insulin resistant states

Answer 28

increased delivery of fatty acids to liver via increased lipolysis due to increased HSL activity in adipose

Question 29

what happens in adipose and muscle tissue in insulin resistant states

Answer 29

VLDL remnant particles have increased triglyceride content due to reduction in LpL activity = increased blood TAGs

Question 30

treatment of type 2 diabetes

Answer 30

lifestyle changes

drugs = e.g metformin

Question 31

how does endurance training enhance your glucose tolerance

Answer 31

exercise will increase your insulin sensitivity

Question 32

what does the drug Metformin inhibit and what does this slow

Answer 32

mitochondrial electron complex 1, slows ETC and reduces ATP production

Question 33

as Metformin reduces ATP production what will increase

Answer 33

AMP will increase

Question 34

what will increased AMP levels increase and what will that activate

Answer 34

increased AMP will increase AMPK, which will activate transcription factors that will impact proteins in the gluconeogenesis pathway

Question 35

what will increased AMPK down regulate

Answer 35

mGPD enzyme (glycogen phosphate dehydrogenase)

Question 36

what will decreased mGPD do

Answer 36

increase NADH, meaning more lactate will be formed