Hormone Regulation and Metabolism Flashcards
what type of signals integrate and coordinate the metabolic activities of different tissues?
hormonal signals
what are hormones?
small molecules/proteins that are produced in one tissue. They are released into the circulation and carried to other tissues
What do hormones act through in order to bring about changes in cellular activity?
receptors
what do hormones coordinate?
metabolic activities of several tissues or organs
what are the 3 classifications of hormone actions?
autocrine
paracrine
endocrine
what can hormones be classified by?
the way they get from their point of release to their target tissue
how do autocrine hormones work?
self signalling - affect the same cell that releases them, binding to receptors on the cell surface
how do paracrine hormones work?
adjacent signalling - released into the extracellular space and diffuse to neighboring target cells
what neighboring target cells of paracrine hormones known as?
eicosanoids
how do endocrine hormones work?
distant signalling - released into the blood and carried to target cells throughout the body
give 2 examples of endocrine hormones
insulin and glucagon
what do hormones bind to?
intra and extra cellular receptors in cells
what are hormonal modes of action?
which receptors they bind to
what are the 3 fuel reserves of mammals?
glycogen stored in the liver and in smaller quantities in muscles
large quantities of triacylglycerols (TAGs) in adipose tissues
tissue proteins which can be degraded when necessary to provide fuel
define normoglycemic
relatively constant blood glucose levels
how do hormones manage fuel reserves?
make sure they release appropriate amount of glucose and that an appropriate amount of glucose is converted into stored fuel
what are the main hormones that work to maintain blood glucose levels?
insulin
glucagon
adrenaline
glucocorticids
what does insulin do?
signals that blood glucose is too high, causing cells to take up excess glucose from the blood and convert it to glycogen and TAGs for storage
what does glucagon do when released as a hormone?
signals that blood glucose is too low, causing tissues to produce glucose by glycolysis of glycogen, the liver to create glucose by glyconeogenesis and the liver to oxidise fats for energy to preserve glucose
what does adrenaline do when released as a hormone?
signals impending activity from tissues, causing metabolic changes to account for this
what are the metabolic changes caused by adrenaline?
increased heart rate and blood pressure to increase delivery of oxygen to tissues
increased production of glucose for fuel
increased glycolysis in muscle
increased fatty acid mobilisation to increase availability of fatty acids as fuel
what do glucocorticoids do when released as a hormone?
mediate long term responses to stress or starvation
where is cortisol released from?
the adrenal cortex
what metabolic effects does cortisol have?
increases the release of fatty acids from TAG’s
stimulates the breakdown of non-essential muscle proteins
promotes gluconeogenesis in the liver
what are the 5 stages of glucose homeostasis?
- just after a meal levels of blood glucose are high so all tissues can use glucose as an energy source
- 4-16 hours after a meal blood glucose levels have dropped. This is counterbalanced by the conversion of glycogen to glucose and gluconeogenesis in the liver.
- 16-30 hours after a meal the main source of glucose is gluconeogenesis in the liver. Some tissues have had to start to reduce their glucose consumption
- 2-24 days after the last meal, glycogen stores have been depleted and the only source of glucose is gluconeogenesis which now occurs in the liver and kidney. glucose is restricted in many uses and the brain starts to use ketone bodies as a source of energy
- by 24 days, glucose is scarce and ketone bodies are now the main source of energy in the brain
why are tissues still able to use glucose as an energy source 4-16 hours after a meal?
the conversion of glycogen to glucose and gluconeogenesis in the liver
what does the pancreas produce?
digestive enzymes and hormones involved in glucose homeostasis
what are the clusters of cells in the pancreas called?
islets of Langerhans
what do islets of Langerhans contain?
blood vessels, beta cells, alpha cells, § cells
what do pancreatic alpha cells produce?
glucagon
what do pancreatic beta cells produce?
insulin
what do pancreatic § cells produce?
somoastatin
what happens when the blood running through the eyelet cells has high glucose levels?
beta cells secrete insulin into the blood
what happens when the blood running through the eyelet cells has low glucose levels?
the cells secrete glucagon into the blood
describe what happens in beta cells of the pancreas when blood glucose rises
- GLUT2 transporters carry glucose into the beta cells where it is immediately converted to glucose 6-phosphate by glucokinase and enters glycolysis
- with the higher rate of glucose catabolism the ATP concentration increases causing ATP-gated potassium channels in the plasma membrane to close
- reduced exit of potassium from the cell depolarizes the membrane. this opens voltage gated calcium channels
- the resulting increase in cytosolic calcium triggers the release of insulin by exocytosis
what type of feedback loop inhibits hormone release?
negative feedback loop
how does insulin lower blood glucose?
by stimulating glucose uptake by tissues
what is the reduced blood glucose detected by?
the beta cell as diminished flux through the hexokinase reaction
what effect does the hexokinase reaction have on insulin release?
slows or stops insulin release
what does the pancreas secrete to allow glucose to enter the cells and be converted to glycogen for storage?
insulin
after eating glucose, what enters the liver by the blood stream and the lymphatic system?
glucose and fatty acids (liver) amino acids (lymphatic system)
what happens in the liver after eating glucose?
most glucose is converted to glycogen
some glucose in the liver and fatty acids is converted to TAGs for longer term storage
excess amino acids are converted to pyruvate and acetyl-CoA to also be converted to TAGs
what are TAGs exported to from the liver?
adipose tissues
what types of cells are stimulated to take up glucose by insulin?
muscle and adipose cells
what happens in the fasting state in the pancreas?
secretes glucagon to trigger the release of glucose from glycogen
After some hours without a meal what organ becomes the main source of glucose for the brain?
liver
during the fasted state what molecules are used for gluconeogenesis?
amino acids from the degradation of proteins in liver and muscle and glycerol from the breakdown of triacylglycerols in adipose tissues
what is the glucose from gluconeogenesis exported to in the fasted state?
the brain
what does the liver use as it’s principal fuel during the fasted state?
fatty acids and excess acetyl-CoA is converted to ketone bodies for export to other tissues
what happens when glycogen stores are depleted?
the body produces more glucose by glyconeogenesis and ketone bodies are synthesised from fatty acids to provide fuel for the brain
describe what happens in the body during the starved state
- proteins degraded to glucogenic AA’s where the carbon skeleton enters the citric acid cycle
- urea from proteins is excreted by the kidneys
- the citric acid intermediate oxaloacetate is diverted to gluconeogenesis
- the glucose produced is exported to the brain via the blood stream
- fatty acids from adipose tissues are oxidised as fuel and acetyl CoA
- the lack of oxaloacetate in the citric acid cycle causes acetyl-CoA to accumulate
- the accumulated acetyl-CoA is converted to acetoacetyl-CoA for ketone body synthesis
- the ketone bodies are exported to the brain via the blood stream
- excess ketone bodies end up in the urine
what happens when fat reserves are gone?
degradation of essential proteins begins- this leads to a loss of heart and liver function and, in prolonged starvation, death
what is diabetes mellitus caused by?
a malfunction of the regulation of glucose metabolism by insulin
what are the two types of diabetes mellitus?
type 1 (insulin dependant) type 2 (non-insulin dependant)
which type of diabetes mellitus is most common in dogs?
type 1
what is type 1 diabetes mellitus caused by?
a failure of the pancreas to produce or secrete insulin
how is type 1 diabetes mellitus treated?
insulin injections
which type of diabetes mellitus is most common in cats?
type 2
what is type 2 diabetes mellitus caused by?
failure of the body to respond to insulin
how is type 2 diabetes mellitus treated?
diet, drugs and insulin injections
Is type 1 diabetes mellitus early or late onset?
early
Is type 2 diabetes mellitus early or late onset?
late
are the symptoms of type 1 diabetes severe or mild?
severe quickly
are the symptoms of type 2 diabetes severe or mild?
mild and can go unnoticed at first
how is diabetes diagnosed?
alongside detection of glucose in urine a glucose tolerance test should be done to monitor the blood glucose of patients after eating
what happens during a glucose tolerance test?
the patient fasts overnight and has a high glucose drink/meal
the blood glucose levels are measured before the meal and at 30 minute intervals for a few hours after
what happens in the healthy individual after a glucose tolerance test?
there is a small spike in blood glucose 30 minutes after the meal, but the glucose normalises within an hour
what happens in the diabetic patient after a glucose tolerance test?
glucose levels start higher and continue to rise well above the normal renal threshold for glucose and do not return to a normal baseline.
what is the renal threshold for glucose?
10mmol/l
what can changes in insulin/glucagon ratio affect?
carbohydrate and TAG metabolism
what can decreases in insulin and glucagon ratio lead to?
carbohydrate metabolism and triglyceride metabolism
what is hyperglycemia caused by?
decreased glucose uptake by muscle and adipose tissue. Increased glycogen breakdown and increased glyconeogenesis.
what is ketoacidosis?
increased lipolysis, increased fatty acid oxidation and increased ketone body production
what is obesity the result of?
taking in more calories in the diet than are expended by the bodies fuel-consuming activities
how does the body deal with excess dietary calories?
convert excess fuel to fat and store it in adipose tissue
burn excess fuel by extra exercise
waste fuel by diverting it to heat production
what does obesity increase the risk of?
diabetes, heart disease, respiratory distress, high blood pressure and some cancers
how many dogs, cats and rabbits in the UK are overweight?
1 in 3 dogs, 1 in 4 cats, 1 in 4 rabbits
what are adipokines?
peptide hormones produced by adipose tissues that carry information about energy reserves stored in adipose tissues to other tissues and the brain.
what are the 2 main types of adipokines?
leptin
adiponectin
what does leptin do?
acts on the hypothalamus to reduce appetite
what message is carried by leptin?
that fat reserves are sufficient, promotes reduction in fuel intake and promotes increasing expenditure of energy
what hormones does leptin stimulate the production of?
anorexigenic peptide hormones (e.g. alpha melanocyte stimulating hormone)
what do anorexigenic peptide hormones do?
decrease appetite
what does leptin inhibit the production of?
orexigenic hormones (e.g. neuropeptide Y)
what do orexigenic hormones do?
increase appetite
what problems can defects in leptin production cause?
high plasma cortisol levels inability to stay warm unrestrained appetite abnormal growth no reproduction severely obese metabolic disturbances similar to those seen in diabetes insulin-resistant
what can cause the same symptoms as defects in leptin production?
defect in leptin receptors
what has the leptin system evolved to regulate?
the starvation response
what is the effect of reduced levels of leptin?
reduces thermogenesis
decreased production of thyroid hormone
decreased production of sex hormones
increased production of glucocorticoids
what is the effect of reduced thermogenesis due to leptin regulation of starvation?
allows fuel conservation
what is the effect of decreased production of thyroid hormone due to leptin regulation of starvation?
slowing basal metabolism
what is the effect of decreased production of sex hormones due to leptin regulation of starvation?
prevention of reproduction
what is the effect of increased production of glucocorticoids due to leptin regulation of starvation?
mobilising the bodies fuel-generating resources
what are the 7 main effects of adiponectin?
affects the metabolism of fatty acids and carbohydrates in the liver and muscle
sensitising other organs to the effect of insulin
increasing the uptake of fatty acids from the blood by muscle cells
increasing the rate of beta oxidation of fatty acids in the muscle
blocking fatty acids synthesis and gluconeogenesis in hepatocytes (liver cells)
stimulating glucose uptake and catabolism in the muscle and liver
protecting against atherosclerosis (build up of fat in the arteries
inhibiting inflammatory responses
what is short term eating behavior influenced by?
ghrelin
PYY 3-36
where is ghrelin produced?
in cells lining the stomach
what does ghrelin stimulate?
appetite
does ghrelin work on a shorter or longer timescale than leptin or insulin?
shorter (between meals)
what is PYY 3-36 produced by?
endocrine cells in the lining of the small intestine and colon
what is PYY 3-36 released in response to?
food entering the small intestine and colon from the stomach
where is PYY 3-36 carried to in the blood?
arcuate nucleus
what does PYY 3-36 do once at the arcuate nucleus?
acts on orexigenic neurons, inhibiting NPY release and reducing hunger
what happens to humans injected with PYY 3-36?
feel little hunger and eat less than normal amounts for about 12 hours
how is concentration of glucose in the blood regulated?
by hormones
what does high blood glucose induce?
release of insulin
what effect does release of insulin by high blood glucose have?
speeds the uptake of glucose by tissues
favors the storage of fuels as glycogen and triacylglycerols
inhibits fatty acid mobilisation in adipose tissues
what does low blood sugar trigger the release of?
glucagon
what effect does release of glucagon by low blood glucose have?
stimulates glucose release from liver glycogen
shifts fuel metabolism in liver and muscle to fatty acid oxidation
in prolonged fasting, triacylglycerols become the main fuel - the liver converts the fatty acids to ketone bodies for export to other tissues, including the brain
what does adrenaline do in the body?
prepares the body for increased activity by mobilising glucose from glycogen and other precursors, releasing it into the blood
what does cortisol stimulate?
gluconeogenesis from amino acids and glycerol in the liver, thus raising blood glucose
what happens in diabetes sufferers?
insulin is either not produced or not recognised by tissues and the uptake of blood glucose is compromised
what hormone does adipose tissue produce?
leptin
what does leptin do?
regulates feeding behaviour and energy expenditure to maintain adequate fat reserves
what does leptin production and release increase with?
the number and size of adipocytes
what receptors does leptin act on?
those in the arcuarate nucleus of the hypothalamus causing the release of anorexigenic (appetite suppressing peptides), including a-MSH, that inhibit eating
what does adiponectin stimulate?
fatty acid uptake and oxidation
what does adiponectin inhibit?
fatty acid synthesis
what does ghrelin act on to produce hunger before a meal?
orexigenic (appetite stimulating) neurons in the hypothalamus
what does PYY3-36 do?
lessens hunger after a meal
