Lecture 28: Glucose metabolism, energy balance and obesity Flashcards
What two things to we need to take into account when considering our energy balance?
energy consumption
energy expenditure
What are the only three macronutrients that contribute to energy consumption?
carbohydrates
protein
fat
How much energy per gram is there in carbohydrates?
17kJ/g
How much energy per gram is there in protein?
17kJ/g
How much energy is there per gram in fat?
37kJ/g
What four things contribute to energy expenditure?
basal metabolic rate
thermogenesis
locomotion
growth
How can we increase our basal metabolic rate?
by doing exercise
What is the main form of energy in our body?
glucose
Glucose is a _____saccharide with 6 rings
mono
What is hypoglycaemia and what does it cause?
low blood sugar, causing dizziness, decreased CNS function, coma and death
What is hyperglycaemia and what does it cause?
high blood glucose levels causing osmotic diuresis, dehydration, vascular collapse, death
Glucose metabolism maintains blood glucose levels at what?
between 4 and 6mM
When we first ingest glucose, it is converted to what? What does this produce?
it is converted into pyruvic acid which produces 2 ATP
When no oxygen is present, what happens to the pyruvic acid?
it undergoes anaerobic respiration and produces lactic acid
When there is oxygen available, what happens to the pyruvic acid?
It is able to go on and produce 36 ATP
In the presence of O2, how may ATP are produced from glucose?
38
How long does glycogen stay in the liver in storage?
24-48 hours
What is the main storage of energy? Why is this?
the main storage is fat and this is because it is lighter and stores more energy
What are the two storage forms of energy?
glycogen
fat
When is the absorptive state?
when we are eating
During the absorptive state, amino acids are converted into what?
proteins
During the absorptive state, fatty acids are converted into what?
triglycerides
During the absorptive state, α-glycerol is converted into what?
triglycerides
During the absorptive state, glucose is converted into what?
glycogen
During the absorptive state, most cells convert glucose into what?
carbon dioxide and water and energy
During the absorptive state, glucose is converted to what?
glycogen (in the liver) and fat
During the absorptive state, is it anabolic or catabolic and is there high insulin or high glucagon?
anabolic
high insulin
During the post-absorptive state, is it anabolic or catabolic and is there high insulin or high glucagon?
catabolic
high glucagon
In the post-absorptive state, proteins are converted to what?
amino acids
In the post-absorptive state, triglycerides are converted to what?
glycerol and fatty acids
In the post-absorptive state, glycogen is converted to what?
What is this process called?
glucose (glycogenolysis)
In the post-absorptive state, most cells convert fatty acids and ketones into what?
carbon dioxide and water and energy
In the post-absorptive state, liver cells convert pyruvate, lactate, glycerol and amino acids into what?
What is this process called?
glucose (gluconeogenesis)
What are the two functions of the pancreas?
endocrine (2%) and exocrine (98%)
Describe the exocrine function of the pancreas
it produces enzymes to be excreted into the gastrointestinal tract to help with digestion
Describe the endocrine function of the pancreas
it secretes hormones into the blood
What three hormones does the pancreas secrete?
insulin
glucagon
somatostatin
Which cells secrete insulin?
β cells
Which cells secrete glucagon?
α cells
Which cells secrete somatostatin?
delta cells
Where are the three types of cells of the pancreas located?
in the Islet’s of Langerhans
Describe the control of insulin secretion
When we eat, the plasma glucose concentration increases which stimulates the β cells in the Islets of Langerhans to secrete insulin.
Briefly, what does insulin cause?
it causes glucose uptake into adipocytes and muscle cells
it also stops glucose being released from the liver which causes a net glucose uptake
What is the purpose of insulin?
to lower the plasma glucose concentration and restores it to normal
What effect does insulin have on the muscle cells?
it stimulates the uptake of glucose into muscle cells
Uptake of glucose into muscle and adipose tissue is mediated by what?
GLUT4
glucose transporter 4
What effect does insulin have on the liver?
it stops the release of glucose and stops the conversion of glycogen to glucose
it also stops ketoacids from being released from the liver
What effect does insulin have on the adipose tissue?
it stimulates the uptake of glucose into the liver cell and stops the breakdown of triglycerides into free fatty acids so free fatty acids are not released.
Where is the insulin receptor located?
on the muscle and fat cells
What type of receptor is the insulin receptor?
a tyrosine kinase receptor
What does the insulin receptor do when insulin binds?
it autophosphorylates tyrosine then the receptor conveys the signal
Describe the make-up of the insulin receptor
there are 2 extracellular α chains where insulin binds, 2 transmembrane domains and 2 intracellular domains (the membrane spanning domains which are in the membrane and intracellularly are β chains)
What is the role of GLUT4 and what is this facilitated by?
its role is to regulate glucose uptake but this is facilitated by the first insulin receptor
When insulin binds to the receptor, what happens?
There is ______________ of the receptor and activation of an i__________ m___________ (i_________ r__________ substrate). This can be p____________ on many sites and can regulate an i___________ s__________ c___________ to convey the signal of insulin.
There is autophosphorylation of the receptor and activation of an intermediate molecule (insulin receptor substrate). This can be phosphorylated on many sites and can be regulate an intracellular signalling cascade to convey the signal of insulin.
What does the intracellular cascade cause?
It activates G_______ which translocates to the membrane to take up g_______. It also acts intracellularly on t_______ e________ that convert glucose into g_______ or p_________. It can also cause t__________ f________ to stimulate insulin receptor r_________e _________ which bind to DNA and then get other enzymes produced
It activates GLUT4 which translocates to the membrane to take up glucose. It also acts intracellularly on target enzymes that convert glucose into glycogen or pyruvate. It can also cause transcription factors to stimulate insulin receptor response elements which bind to DNA and then get other enzymes produced
Insulin increases cellular glucose uptake BECAUSE insulin stimulates the translocation of glucose transporter 4 (GLUT4) to the cell membrane
both are true and the second causes the first
What does GLUT 2 do?
it detects glucose and regulates the release of insulin from the β cells
Describe the process of insulin secretion
Plasma glucose is detected by ________ ___ transporter and glucose enters the β cell. This activates _________ to convert glucose into _______________ which is then converted to ________ and __________. ADP is converted to ATP and this energy causes the closure of _________ channels. This opens voltage gated _________ channels which causes an influx of Ca2+. The Ca2+ causes a release of __________ from vesicles
Plasma glucose is detected by GLUT 2 transporter and glucose enters the β cell. This activates glucokinase to convert glucose into glucose-6-phosphate which is then converted to pyruvate and NADPH. ADP is converted to ATP and this energy causes the closure of K+ channels. This opens voltage gated Ca2+ channels which causes an influx of Ca2+ channels. The Ca2+ causes a release of insulin from vesicles
When glucose enters the β cell, what is the rate limiting enzyme?
glucokinase
What other things can stimulate the release of insulin from β cells and how does this occur?
- C____ and A______ activate p________________ _____ which can indirectly activate C_______ which increases insulin release
- they can also be converted to d__________ and activation of p_________ k__________ _______ to also release insulin
- G_________, G_________, β___________ act to release insulin through a stimulatory G-protein
- CCK and ACh activate phospholipase C which can indirectly activate Ca2+ which increases insulin release
- they can also be converted to diacylglycerol and activation of protein kinase C to also release insulin
- glucagon, GLP-1, β-adrenergy act to release insulin through a stimulatory G-protein
What things can inhibit the release of insulin from the β cells and how does this occur?
_________ and __________ stimulate an _______ G-protein which stops release of insulin
SS and α-adrenergy stimulate an inhibitory G-protein which stops release of insulin
Does increasing cAMP increase or decrease the release of insulin?
it increases the release
What is the incretin effect?
this is when orally ingested glucose leads to a large increase in insulin secretion but intravenous (injected) leads to less insulin being released
Why do glucose levels rise and then fall quickly after we eat a meal?
because insulin is released
What does the incretin effect tell us?
That something happens in the gut that increases insulin secretion because in the gut, there are 2 other hormones are produced
What are the 2 other hormones that are produced int he gut that are needed to enhance insulin secretion?
Glucagon-like peptide (GLP1) and glucose-dependent insulinotropic peptide (GIP) enhance effect on insulin release
What is the purpose of glucagon?
to increase glucose levels
What is glucagon and where is is produced/secreted from?
it is a peptide hormone which is produced by the α cells in the Islet’s of Langerhans that opposes insulin actions
What are the three actions of glucagon?
- increases glycogenolysis (liberating glucose)
- increasing gluconeogenesis (synthesising glucose)
- increase ketone synthesis
How are glucagon actions mediated?
they are mediated via a G-protein coupled receptor to activate adenylate cyclase and protein-kinase A
Describe the control of glucagon secretion
There is a decrease in plasma glucose which is detected by the pancreatic islet α cells and this leads to an increase in glucagon secretion which increases plasma glucagon and this causes an increase in glycogenolysis, gluconeogenesis, ketone synthesis in the liver. This leads to an increase in plasma glucose and plasma ketones
Describe how the levels of glucose, insulin and glucagon changes after we eat food?
Immediately after we eat, our glucose levels are high and so our insulin levels are high and glucagon levels are low. As we go from the absorptive state to the post-absorptive state, the glucose level drops and so glucagon is released and the levels of glucagon rises. This is to keep insulin at a controlled level
What are the two types of diabetes and what causes them?
- type 1: a loss of β cells in the pancreas leading to a deficiency in insulin
- type 2: due to insulin resistance or reduced insulin sensitivity
How can obesity lead to diabetes?
If you keep eating, insulin is continually high and so the receptors become resistant to it and so the pancreatic β cells keep producing and secreting it and eventually they die
As well as acting on on the muscle and fat cells, where else does insulin act?
on the brain
How does insulin affect the brain?
There are insulin receptors in the brain which activates a pathway and we can use this to reduce food intake
How does the brain control insulin release?
the brain control the liver and the liver produces glucose which would affect the insulin released