L4 Metabolic Regulation Flashcards
Absorptive state
period when ingested nutrients are entering the blood from the GI tract, occurs DURING meal digestion
Postabsorptive state
period when the GI tract is empty of nutrients, therefore energy must be supplied from catabolism of body stores
normal blood glucose concentration must be maintained
True fasting
no food for 24 hours
Digestion
not equivalent to absorption
breakdown of food into molecules small enough to be absorbed, accomplished by enzymes
Absorption
movement of food molecules from the GI tract into the blood
digestion occurs before absorption
Carb & Protein absorption
breakdown of these products are absorbed by the GI tract directly into the blood, circulates to the liver via the portal vein and then into systemic circulation
Fat absorption
- ingested fats are emulsified by bile salts
- gut cells transform fats into chylomicrons
- Travel to the blood via lymph system, end up in adipose and muscle
- Broken down into FFA and chylomicron remnant
Chylomicrons
enable fats to move within the aqueous environment of blood
travel through lymph vessels/lacteals to use lymph to enter the blood via the thoracic duct
chylomicron remnants become VLDLS to be resecreted into the blood
What happens to absorbed glucose
Enters cells to become ATP if energy is needed
Energy not needed: make fat or make glycogen in muscle and liver
What happens to glucose in the liver?
- Made into glycogen
- Processed to form triglycerides
- MOST is packaged to form VLDLs, which are then stored as triglycerides
VLDLs and Triglyceride storage
VLDL is made of cholesterol and triglycerides
Adipose tissue contains lots of lipoprotein lipase, which breaks down VLDL
VLDL becomes fatty acid and monoglyceride (remains in blood and are metabolized by liver)
What happens to absorbed triglycerides?
absorbed fat becomes stored fat
Comes from the chylomicrons that transfer FFA to adipose tissue
lipoprotein lipase breaks down these into FFA, monoglycerides, chylomicron remnants.
absorbed fat from your food becomes stored as fat in adipose tissue
What happens to absorbed amino acids?
- Majority are taken up by cells for protein synthesis
- Others enter the liver to make liver proteins, plasma proteins, or keto acids
- Protein only replaces protein that was lost in postabsorptive state
- Any excess becomes stored as fat
Summary of absorptive state
- most of cells energy needs are provided by absorbed glucose
- Some glucose is stored as glycogen in liver and skeletal, most excess is stored as fat
- There is a net uptake of glucose by the liver
- Synthesis of body proteins, much of dietary protein is used for energy or converted to fat
As the absorptive state ends…
net synthesis ceases
net catabolism begins
Events that maintain normal blood glucose during postabsorptive state
- Processes that provide sources of blood glucose (Glycogenolysis, Gluconeogenesis from fat or protein)
- Increased fat utilization, which spares glucose
Glycogenolysis
from liver directly
muscle only indirectly via cori cycle
Gluconeogenesis
pyruvate, lactate, glycerol, amino acids
from fat = only glycerol
from protein = few hours into postabsorptive state, AA become source of blood glucose. large quantities of protein can be catabolized from muscles if needed
Glucose sparing
Includes all processes that enable to utilize fat for energy vs glucose in postabsorptive state, accelerated lipolysis is necessary
Most tissues use GLUCOSE in absorptive state
Most tissues use FAT in post absorptive
Summary of postabsorptive
- Glycogen, fat, protein anabolism are curtailed, net catabolism begins
- Glucose is formed by glycogenolysis and gluconeogenesis
- Accelerated lipolysis releases FFA into blood, through beta oxidation, and ketones
- Brain uses glucose and ketones
Hormonal regulation of metabolsim
The most important regulators with respect are 2 peptide hormones, both produced and released from islets of langerhans in pancreas
insulin = beta
glucagon = alpha
Insulin
anabolic hormone of absorptive state
Secretion INCREASES during absorptive
Secretion DECREASES during postabsorptive
has two actions, metabolic and growth-promoting effects
Metabolic effects of insulin
effects on carbohydrates, lipid, and protein synthesis
What occurs after a meal?
- Plasma glucose concentration rises, stimulates insulin secretion from beta pancreatic cells
- Insulin is released into the blood and binds to muscle, fat, and liver cells, resulting in glucose being taken up
- Insulin inhibits gluconeogenesis in the liver
- Blood glucose level decreases, which serves as a negative feedback signal
GLUT4 transporters
when insulin binds to its receptor, signal transduction pathway leads to movement of glucose transporters from inside of cell to surface of cell
GLUT4 transporters move glucose from blood into the cell
the more glucose transporters in the cell membrane, the more glucose that can be taken up by the cell
What stimulates insulin release?
high blood glucose
high blood amino acid
activation of parasympathetic nerves to islets
peptides secreted from GI tract due to eating
What inhibits insulin secretion?
activation of sympathetic nerves to islets
and/or increase in circulating epinephrine
Glucagon
hormone of the postabsorptive state
overall effect of glucagon is to increase plasma glucose concentration
main target organ is the liver
Main effects of glucagon
increases glycogen breakdown
increases gluconeogenesis
promotes ketone synthesis
Plasma concentrations in the postabsorptive state
plasma glucose is low
glucagon is high
insulin is low
Regulators of glucagon secretion
Low blood glucose concentration is the major stimulus
sympathetic innervation to islets stimulates glucagon secretion
circulating epinephrine stimulates glucagon secretion
What’s happening when you become hypoglycemic?
Glucagon secretion and activation of the SNS
hormonal and neural responses
insulin is low, glucagon is high
hypothalamus mediates the response
increased SNS causes increased glycogenolysis, gluconeogensis, lipolysis
increase in plasma glucose, fatty acids, glycerol
Additional hormones that regulate metabolism
Cortisol and Growth hormone
their secretion is not strictly tied to transition between absorptive and postabsorptive states
both produce actions that are opposite to insulin, they both increase blood glucose levels
Cortisol
many metabolic reactions cannot occur unless a small amount of cortisol is present
cortisol is necessary to maintain necessary concentrations of enzymes required for gluconeogensis and lipolysis
cortisol also plays a role in counter regulatory mechanisms that protect against hypoglycemia
What does cortisol do?
it is catabolic
increases protein catabolism
increases fat catabolism
increases gluconeogenesis
net result = increased plasma concentration of AA, glucose, FFA = fuel in the blood!
Growth hormone
stimulate growth and protein synthesis
has minor effects on metabolism, severe changes in amounts affects carb/lipid metabolism
can increase gluconeogenesis, reduces isulins ability to promote glucose uptake
Counter-regulatory hormones
hormones that have effects opposite to insulin
glucagon, cortisol, growth hormone, epinephrine
they are the ones that save your life during times of fasting, because they raise plasma glucose levels
Similarities in Postabsorptive and Exercise state
Both have an increase in SNS, increased levels of glucagon, cortisol, GH, low plasma insulin
Fuel during exercise
during exercise, large quantities of fuel must be mobilized to provide energy for muscle contraction
major sources are plasma glucose and FFA, muscle glycogen
Plasma glucose during exercise
SHORT TERM: remains unchanged for 50 min
LONG TERM: falls about 25% 4 hrs
Plasmas Concentrations during exercise
Glucagon–> increases with a trigger of low glucose
Insulin–> preprogrammed actions, preparing for the changes in the body
Lipolysis is increasing as this is happening
Changes during exercise
- All exercise intensities cause SNS activity increases and circulating epinephrine increases
- These changes are independent of blood glucose levels, they are a part of preprogrammed response to exercise
- During prolonged exercise, hypoglycemia stimulates glucagon secretion
- Exercise inhibits insulin secretion
What is the time course of fuel utilization during mild/moderate intensity exercise?
- During a brief period of moderate exercise, energy is derived from carbs and lipids equally
- As exercise continues, glycogen decreases, blood glucose becomes main source
- With increasing time, glucose utilization may outpace gluconeogensis and glycogen stores are depleting. Hypoglycemia is what triggers glucaogn secretion
- After 1 hr, gradual increase in utilization of lipid for energy
Lipid utilization during exercise
increases as exercise duration increases
during 1st 40-90 min = 40% of energy comes from FFA
by 4th hour of exercise, lipid is 62%
Very long exercise , FFA supplies 80%
Hitting the wall
-glycogen depleted state
-work capacity progressively decreases
-due to a slower rate of energy released from lipid, compared to carb catabolism
S/S: weakness, fatigue, dizziness
Techniques to prevent hitting the wall
- Consume carbs during exercise
- Consume carbs before exercise
- Decrease exercise intensity
Consume carbs before exercise
Helps to maximize initial glycogen levels in muscles
includes combo of increasing complex carb intake and decreasing training intensity during few days before event
recommended for events that last more than 60-90min
Decrease exercise intensity
Lowers total energy requirements
also lowers the percentage of energy that comes from glycogen
Lipid and exercise intensity
Lipid utilization increases as exercise intensity decreases
-Mild exercise intensities have main source as lipids
-
Lipid and training
Lipid utilization increases as training increases
more aerobically trained individuals use more plasma FFA and conserve glycogen stores
Why? have increased # of enzymes involved in FFA use, improve transport of FFA through membrane, proliferation of capillaries in trained muscle
Immediate energy…
ATP-CP system
walking briskly for 1 min
all out exercise for 6 sec
uses Stored ATP
Short term energy…
anaerobic glycolysis
all out exercise for 1-2 minutes
uses blood glucose
Long-term energy…
aerobic metabolism
prolonged exercise
uses kreb cycle
Short-term energy transfer system
Provided by anaerobic glycolysis and lactate production
allows for rapid ATP formation, not as fast as ATP-CP
has a power output of 45% of the immediate energy system
Blood lactate accumulation
Most rapid and highest lactate levels are reached during 1-2 minutes of all out exercise
lactate is formed continuously at rest and during exercise
in aerobic, lactate production rate matches lactate removal rate
blood lactate rises exponentially at 55% of healthy untrained VO2 max
Aerobic conditioning and lactate levels
Lactate marks anaerobic system uses or the limit of aerobic production of ATP
Aerobic conditioning causes:
1. production of less lactate
2. increased rate of lactate removal
3. increased capillarization
4. Increased mitochondrial density
5. Increased concentration of enzymes
6. Increased intramuscular glycogen stores
Factors related to lactate threshold
low tissue O2
reliance on glycolysis
activation of fast-twitch muscle fibers
reduced lactate removal
Long-term energy system
source is aerobic metabolism
-O2 uptake rises exponentially during first minute of moderate exercise
-plateaus to reach steady state
-theoretically, you can continue indefinitely at this level
Steady-state
balance between energy requirements and ATP production by aerobic metabolism
lactate produced is oxidized
