11) ****Hormonal Control of Metabolism During Exercise**** Flashcards
What are four major endocrine glands responsible for metabolic regulation during rest and exercise?
- Anterior Pituitary Gland
- Thyroid Gland
- Adrenal Gland
- Pancreas
Hormones released by these glands affect/regulate exercise metabolism of carbohydrates and fat
Exercise causes a hormonal response in order to: (3)
(1) Increase the availability of glucose to fuel exercise
(2) Increase Cardiovascular function to better perfuse the body with blood
(3) Prevent dehydration and electrolyte imbalances
(1) Increase the availability of glucose to fuel exercise
- CHO and Fat metabolism are responsible for maintaining MM ATP during prolonged exercise
- Hormones work to ensure adequate glucose and free fatty acid availability for MM energy metabolism
(2) Increase Cardiovascular function to better perfuse the body with blood
(3) Prevent dehydration and electrolyte imbalances
Anterior Pituitary gland secretes hormones in response to ?
Anterior pituitary gland secretes hormones in response to stimulatory and inhibitory hormones from the hypothalamus
Exercise is a strong stimulus of the hypothalamus as it increases the release of all anterior pituitary hormones
The Anterior Pituitary Releases ?
The Anterior Pituitary Releases Growth Hormone
GH:
- builds tissues and organs
- Promotes MM hypertrophy
- Increases Fat Metabolism and FFA for glucose sparing
Three basic roles of Growth Hormone?
Which gland releases GH?
GH is released by the anterior pituitary in response to hormones released from the hypothalamus triggered by exercise
GH:
- builds tissues and organs
- Promotes MM hypertrophy (via IGF-1)
- Spares glucose by increasing fat metabolism and FFA
Regulation of Metabolism: Thyroid gland
The thyroid gland secretes ? and ?
The thyroid gland secretes triiodothyronin (T3) and Thyroxine (T4)
Increases:
- Metabolic rates of all tissues
- Protein Synthesis
- Glucose uptake by cells
- Glycolysis and Gluconeogenesis
- Fatty acid availability for aerobic metabolism
- Number and size of mitochondria (long-term effect)
The thyroid gland secretes triiodothyronin (T3) and Thyroxine (T4)
Increases:
- ? of all tissues
- ?
- ? uptake by cells
- ? and ?
- ? availability for aerobic metabolism
- Number and size of ?
The thyroid gland secretes triiodothyronin (T3) and Thyroxine (T4)
Increases:
- Metabolic rates of all tissues
- Protein Synthesis
- Glucose uptake by cells
- Glycolysis and Gluconeogenesis
- Fatty acid availability for aerobic metabolism
- Number and size of mitochondria (long-term effect)
Regulation of Metabolism: Adrenal Gland
Adrenal Medulla releases ?
Adrenal Medulla releases catecholamines (epinephrine (80%) and norepinephrine (20%)**
exercise → increase in sympathetic nervous system activity → stimulates release of E/NE from Adrenal Medulla
Regulation of Metabolism: Adrenal Gland
Adrenal Medulla releases catecholamines (epinephrine and norepinephrine)
Which lead to Increases in: (6)
Adrenal Medulla releases catecholamines (epinephrine and norepinephrine)
Which lead to Increases in:
- Respiration
- Heart Rate, contractility, BP
- Metabolism
- Glycogenolysis (b/d of glycogen to ↑ Glucose)
- Availability of blood glucose and FFA
- Redistribution of blood flow to Active Skeletal MM
exercise → increase in sympathetic nervous system activity → stimulates release of E/NE from Adrenal Medulla
The Adrenal Cortex Releases ?
The Adrenal Cortex Releases corticosteroid hormones
(Glucocorticoids such as cortisol)
Affects of Cortisol
Increases:
- Gluconeogenesis
- FFA availability
- Protein Catabolism
Decreases:
- Glycolysis (sparing glucose for brain)
- Immune Reactions (acts as an anti-inflammatory)
Overall: Preserve Glucose for the brain by providing other glucose sources / FFA
Cortisol is released from the ?
What are the affects of Cortisol on metabolism?
Increases (3)
Decreases (2)
Cortisol is released from the Adrenal Cortex
Affects of Cortisol
Increases:
- Gluconeogenesis
- FFA availability
- Protein Catabolism
Decreases:
- Glycolysis (sparing glucose for brain)
- Immune Reactions (acts as an anti-inflammatory)
Overall: Preserve Glucose for the brain by providing other glucose sources / FFA
Regulation of Metabolism: Pancreas
The pancreas releases ? and ?
The pancreas releases insulin and glucagon
The ? releases insulin and glucagon
The pancreas releases insulin and glucagon
Insulin (released from ?) is ?anabolic or catabolic?
- Released in response to ?
- Acts to decrease ? by increasing ? by cells (remove from blood)
- Increases synthesis of ?, ?, ?
- Decreases ?
- Decreases ?
Insulin (released from pancreas) is Anabolic
- Released when blood glucose increases
- Acts to decrease blood glucose by increasing glucose uptake by cells (remove from blood)
- Increases synthesis of glycogen, protein, fat
- Decreases lipolysis
- Decreases gluconeogenesis
Role of Testosterone
Is testosterone anabolic or catabolic?
Testosterone is an anabolic steroid (Increases Hypertrophy)
What are 5 critical body processes that are affected by testosterone levels?
(1) Fat distribution
(2) Muscle Mass
(3) Strength development
(4) Bone mass maintenance
(5) Red blood cell production (stimulates erythropoietin)
Testosterone response to resistance exercise and training is greatly influenced by ?
Testosterone response to resistance exercise and training is greatly influenced by the selection of the acute program variable domains: intensity, number of sets, choice of exercise, order of exercise, and rest period duration
- may be a threshold of volume or metabolic demand that must be reached in order to see increased testosterone in response to exercise (ie MM must be stressed)
- The MM mass used will also effect whether there is a response to resistance exercise (small MM mass may not see any effect)
Effect of Testosterone on Adipose Tissue
Testosterone administration to androgen-deficient men is associated with increased ? and reduction in ?
Bioavailable testosterone levels are positively correlated with ? and negatively correlated with ?
Testosterone administration to androgen-deficient men is associated with increased lean body mass and reduction in whole body regional fat mass
Bioavailable testosterone levels are positively correlated with MM Strength and negatively correlated with Fat Mass
↑Testosterone → ↑Strength & ↓Fat Mass
Effect of Testosterone on Adipose Tissue
Testosterone on Adipose Tissue:
- Lowering [testosterone] below baseline increases ? and ? adipose tissue stores in the ? and ?
- Increasing [Testosterone] above baseline induces greater loss of adipose tissue from ? of ? but NOT ?
Testosterone on Adipose Tissue:
- Lowering [testosterone] below baseline increases subcutaneous and deep adipose tissue stores in the appendices and adbdomen
- Increasing [Testosterone] above baseline induces greater loss of adipose tissue from smaller, deeper intermuscular stores of the thigh but NOT intra-abdominal fat
↑Testosterone → ↓ Adipose tissue from thigh but not abdomen
↓ Testosterone → ↑ Subcutaneous & deep Adipose tissue in appendices and abdomen
Testosterone administration to androgen-deficient men is associated with increased lean body mass and reduction in whole body regional fat mass
Bioavailable testosterone levels are positively correlated with MM Strength and negatively correlated with Fat Mass
↑Testosterone → ↑Strength & ↓Fat Mass
Effect of Testosterone on Skeletal MM
Testosterone supplementation improves ? and ? but NOT ? or ?
Skeletal MM: Dose dependent (↑testosterone → greater effect on MM (↑Strength/Power)
Testosterone supplementation improves maximal MM strength and Leg Power but NOT MM fatigability (ie no effect on energy systems) or Specific tension
No change in specific tension indicates ↑Strength/Power is from ↑ MM mass
Experiment: Seated leg press (1-RM) following graded doses of testosterone
* Testosterone administration was associated with a dose-dependent increase in leg press strength and leg power, which correlated with testosterone dose and circulating testosterone concentrations
* No significant effect of testosterone on fatigability
* NO change in specific tension
* No significant change in specific tension indicates that testosterone-induced gains in muscle strength are proportional to the increase in muscle mass
- Effects on MM are linearly correlated with the administered dose and prevalent circulating testosterone concentration
Mechanisms of Anabolic Effects of Testosterone
Define Fiber Hypertrophy
Fiber Hypertrophy = ↑ in cross-sectional area of MM due to ↑ in the size of pre-existing MM fibers (Satellite cell role)
- Dose-dependent ↑ in cross-sectional areas of type I (slow-oxidative) and Type II (Fast-oxidative/glycolytic) MM fibers
- No change in absolute number or relative proportion of fibers (No hyperplasia)
Mechanisms of Anabolic Effects of Testosterone
Hormones such as testosterone cause a Dose-dependent ↑ in cross-sectional areas of ? and ? MM fibers
- No change in ? or ? of fibers
- Dose-dependent ↑ in cross-sectional areas of type I (slow-oxidative) and Type II (Fast-oxidative/glycolytic) MM fibers
- No change in absolute number or relative proportion of fibers (No hyperplasia)
Fiber Hypertrophy = ↑ in cross-sectional area of MM due to ↑ in the size of pre-existing MM fibers (Satellite cell role)
Mechanisms of Anabolic Effects of Testosterone
Increased ? and ? correlates with testosterone concentration
- Testosterone-induced increase in MM volume due to increase in ?
Increased myonuclear Number and fiber cross-sectional area correlates with testosterone concentration
- Testosterone-induced increase in MM volume due to increase in fusion of myoblasts to existing MM fibers
Fiber Hypertrophy = ↑ in cross-sectional area of MM due to ↑ in the size of pre-existing MM fibers (Satellite cell role)
Myoblasts = new MM cells formed from Satellite cells
Mechanisms of Anabolic effects
How does testosterone induce muscle fiber hypertrophy?
Testosterone induces muscle fiber hypertrophy by acting at multiple steps in pathways regulating muscle protein synthesis and breakdown
- Binds to androgen receptors
- Stimulates mesenchymal pluripotent cell commitment into the myogenic (MM) lineage and
- Inhibits differentiation into adipocyte lineage
- Stimulates muscle Protein synthesis
- Inhibits muscle protein degradation
Androgen receptor protein expressed in multiple cell types in skeletal muscle
Mechanisms of Anabolic effects - Testosterone
Testosterone induces muscle fiber hypertrophy by acting at multiple steps in pathways regulating muscle protein synthesis and breakdown
- Binds to ? receptors
- Stimulates mesenchymal pluripotent cell commitment into the ? lineage and
- Inhibits differentiation into ? lineage
- Stimulates muscle ?
- Inhibits muscle ?
Testosterone induces muscle fiber hypertrophy by acting at multiple steps in pathways regulating muscle protein synthesis and breakdown
- Binds to androgen receptors
- Stimulates mesenchymal pluripotent cell commitment into the myogenic (MM) lineage and
- Inhibits differentiation into adipocyte lineage
- Stimulates muscle Protein synthesis
- Inhibits muscle protein degradation
Androgen receptor protein expressed in multiple cell types in skeletal muscle
Testosterone - Satellite cells:
- Stimulates satellite cell replication (↑ number)
- Proportionate ↑ in myonuclear number
- Changes in satellite cell ultrastructure (preparing to become new myoblast)
Mechanisms of Anabolic effects - Testosterone
The effect of Testosterone on Satellite cells:
- Stimulates ?
- Proportionate ↑ in ?
- Changes in ? (preparing to become new myoblast)
The effect of Testosterone on Satellite cells:
- Stimulates satellite cell replication (↑ number)
- Proportionate ↑ in myonuclear number
- Changes in satellite cell ultrastructure (preparing to become new myoblast)
Testosterone induces muscle fiber hypertrophy by acting at multiple steps in pathways regulating muscle protein synthesis and breakdown
- Binds to androgen receptors
- Stimulates mesenchymal pluripotent cell commitment into the myogenic (MM) lineage and
- Inhibits differentiation into adipocyte lineage
- Stimulates muscle Protein synthesis
- Inhibits muscle protein degradation
Motor neurons have androgen receptors, what does this mean in terms of testosterone activity?
(using two experiments as examples)
Exp: Testosterone ↑ number of neurons in the spinal nucleus of the bulbocavernosus early in development in male/female gerbils
- ↑ # neurons innervating the muscle
Exp: Testosterone improves the ↓ in fiber cross-sectional area and the shift from slow to fast fiber type in rats with spinal cord injury
- shifting fiber type and cross-sectional size during sp cord injury
Catabolic Hormones: Muscle Atrophy
What is fiber atrophy?
Breaking down of mm fibers
Catabolic Hormones: Muscle Atrophy
What hormone drives fiber atrophy?
Muscle Atrophy
- Driven by greater cortisol binding (vs testosterone (anabolic) binding on skeletal mm
Breaking down of mm fibers
Cortisol and Testosterone are antagonists
Catabolic Hormones: Muscle Atrophy
How does testosterone binding to skeletal muscle impact the effects of cortisol?
↑ Testosterone binding to skeletal MM blocks the genetic element on DNA that binds cortisol → prevent cortisol binding → prevent atrophy
Muscle Atrophy = Breaking down of mm fibers
- Driven by greater cortisol binding (vs testosterone (anabolic) binding on skeletal mm
Cortisol and Testosterone are antagonists
Catabolic Hormones: Muscle Atrophy
In animal models, ? antagonize the anabolic effects of testosterone
Conversely, testosterone administration can prevent ?
In animal models, glucocorticoids (cortisol) antagonize the anabolic effects of testosterone
Conversely, testosterone administration can prevent glucocorticoid-induced MM atrophy
↑ Testosterone binding to skeletal MM blocks the genetic element on DNA that binds cortisol → prevent cortisol binding → prevent atrophy
Muscle Atrophy = Breaking down of mm fibers
- Driven by greater cortisol binding (vs testosterone (anabolic) binding on skeletal mm
Cortisol and Testosterone are antagonists
Catabolic Hormones: Muscle Atrophy
What might be the role of cortisol release following resistance exercise?
Cortisol release following resistance exercise may improve mm cell remodeling by removing damaged proteins
- help with recovery
Then testosterone and GH induce hypertrophy
Muscle Atrophy = Breaking down of mm fibers
- Driven by greater cortisol binding (vs testosterone (anabolic) binding on skeletal mm
Cortisol and Testosterone are antagonists
- In animal models, glucocorticoids (cortisol) antagonize the anabolic effects of testosterone
- Conversely, testosterone administration can prevent glucocorticoid-induced MM atrophy
↑ Testosterone binding to skeletal MM blocks the genetic element on DNA that binds cortisol → prevent cortisol binding → prevent atrophy
The hypothalamus and the anterior pituitary
Growth hormone:
- Released from ?
- Release stimulated by ? from ?
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
Factors stimulating hypothalamic GHRH release:
- ↑ blood amino acid levels
- ↓ blood glucose levels
- ↓ blood fatty acid levels
- Sleep
- Exercise
- Fasting
Release is proportional to the intensity of exercise (aerobic and resistance)
The hypothalamus and the anterior pituitary
Factors stimulating hypothalamic GHRH release:
- ↑ blood ? levels
- ↓ blood ? levels
- ↓ blood ? levels
- ?
- ?
- ?
Release is proportional to ?
Factors stimulating hypothalamic GHRH release:
- ↑ blood amino acid levels
- ↓ blood glucose levels
- ↓ blood fatty acid levels
- Sleep
- Exercise
- Fasting
Release is proportional to the intensity of exercise (aerobic and resistance)
GHRH - Growth hormone releasing hormone
Sleep and exercise are strongest stimuli
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
The hypothalamus and the anterior pituitary
Effects of GH may be mediated by ?
Effects of GH may be mediated by insulin-like growth factors (IGFs) from liver
GHRH - Growth hormone releasing hormone
Sleep and exercise are strongest stimuli
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
The hypothalamus and the anterior pituitary
Growth hormone levels affected by levels of ? in the blood
- ? secretion
- When is GH secretion highest?
Growth hormone levels affected by levels of nutrients in the blood (Amino acids, glucose, Fatty acids)
- Pulsatile secretion
- Highest secretion while sleeping
GHRH - Growth hormone releasing hormone
Sleep and exercise are strongest stimuli
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
The hypothalamus and the anterior pituitary
Functions of GH:
General:
- ↑ ?
- ↑ ?
- ↑ ?
Counteracts in general the effects of insulin on glucose and lipid metabolism
- ↑ blood ? and ?
Functions of GH:
General:
- ↑ growth
- ↑ cell reproduction
- ↑ metabolism
Counteracts in general the effects of insulin on glucose and lipid metabolism (but shares anabolic properties with insulin)
- ↑ blood glucose and Free fatty acids
GHRH - Growth hormone releasing hormone
Both insulin and GH “build up” MM;
However, where insulin ↓ blood glucose/lipid metabolism, GH works to maintain those levels (counteracts)
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
Growth hormone levels affected by levels of nutrients in the blood (Amino acids, glucose, Fatty acids)
- Pulsatile secretion
- Highest secretion while sleeping
The hypothalamus and the anterior pituitary
9 functions of Growth Hormone related to exercise:
(1) Decreased ? utilization
(2) Increased ?
(3) Increased ? transport
(4) Increased ?
(5) Increased ? utilization
(6) Increased ? synthesis → small ↑ MM size (IGF-1)
(7) Increased ? synthesis
(8) Increased ? function
(9) Increased retention of ?
Functions of GH Related to Exercise:
(1) Decreased glucose utilization (spares glucose to maintain blood glucose levels)
- Opposes actions of insulin (anti-insulin effect; decreased glycogen synthesis) to reduce use of glucose
- Increases synthesis of new glucose in liver (gluconeogenesis)
- Increases mobilization of FFA from adipose tissue
(2) Increased lipolysis (fat metabolism)
- TG → Glycerol + FFA (glycerol for gluconeogenesis, FFA to make ATP)
(3) Increased amino acid transport
- GH → Liver → IGF-1 → increases AA transport
(4) Increased protein synthesis
- facilitates MM growth/hypertrophy
(5) Increased Fatty acid utilization
(6) Increased Collagen synthesis → small ↑ MM size (IGF-1)
(7) Increased cartilage synthesis
(8) Increased immune function = cell mediated immunity // inflammation
(9) Increased retention of nitrogen, sodium, potassium, phosphorous (electrolytes -> retain H2O)
GHRH - Growth hormone releasing hormone
General functions of GH:
- ↑ growth
- ↑ cell reproduction
- ↑ metabolism
Counteracts in general the effects of insulin on glucose and lipid metabolism (but shares anabolic properties with insulin)
- ↑ blood glucose and Free fatty acids
- Both insulin and GH “build up” MM;
—However, where insulin ↓ blood glucose & lipid metabolism, GH works to maintain those levels (counteracts)
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
Growth hormone levels affected by levels of nutrients in the blood (Amino acids, glucose, Fatty acids)
- Pulsatile secretion
- Highest secretion while sleeping
The hypothalamus and the anterior pituitary
What is the function of GH on the liver?
Function of GH on Liver:
- GH acts on liver to increase synthesis of insulin-like growth factor 1 (IGF-1)
- Increases Gluconeogenesis (glycerol from lipolysis into glucose)
GHRH - Growth hormone releasing hormone
General functions of GH:
- ↑ growth
- ↑ cell reproduction
- ↑ metabolism
Counteracts in general the effects of insulin on glucose and lipid metabolism (but shares anabolic properties with insulin)
- ↑ blood glucose and Free fatty acids
- Both insulin and GH “build up” MM;
—However, where insulin ↓ blood glucose & lipid metabolism, GH works to maintain those levels (counteracts)
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
Growth hormone levels affected by levels of nutrients in the blood (Amino acids, glucose, Fatty acids)
- Pulsatile secretion
- Highest secretion while sleeping
The hypothalamus and the anterior pituitary
What is the function of GH on the adipose tissue?
Function of GH on Adipose tissue:
- Increased lipolysis = ↑ release of FFA and glycerol into blood
- Glycerol enters liver → stimulates Gluconeogenesis in liver = produce glucose (from non CHO)
GHRH - Growth hormone releasing hormone
General functions of GH:
- ↑ growth
- ↑ cell reproduction
- ↑ metabolism
Counteracts in general the effects of insulin on glucose and lipid metabolism (but shares anabolic properties with insulin)
- ↑ blood glucose and Free fatty acids
- Both insulin and GH “build up” MM;
—However, where insulin ↓ blood glucose & lipid metabolism, GH works to maintain those levels (counteracts)
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
Growth hormone levels affected by levels of nutrients in the blood (Amino acids, glucose, Fatty acids)
- Pulsatile secretion
- Highest secretion while sleeping
The hypothalamus and the anterior pituitary
Functions of Insulin-like growth factor 1:
- Increased synthesis of ? in mm via altering ?
- Increased synthesis of ? resulting in mm hypertrophy
Functions of Insulin-like growth factor 1:
- Increased synthesis of amino acid channel in mm via altering transcription
- Increased synthesis of contractile proteins (Actin/Myosin) resulting in mm hypertrophy
GHRH - Growth hormone releasing hormone
General functions of GH:
- ↑ growth
- ↑ cell reproduction
- ↑ metabolism
Counteracts in general the effects of insulin on glucose and lipid metabolism (but shares anabolic properties with insulin)
- ↑ blood glucose and Free fatty acids
- Both insulin and GH “build up” MM;
—However, where insulin ↓ blood glucose & lipid metabolism, GH works to maintain those levels (counteracts)
Growth hormone:
- Released from anterior pituitary
- Release stimulated by GHRH from hypothalamus
Growth hormone levels affected by levels of nutrients in the blood (Amino acids, glucose, Fatty acids)
- Pulsatile secretion
- Highest secretion while sleeping
Acute Aerobic Exercise and GH release
GH release is proportional to exercise ? for both aerobic and resistance exercise
Acute ? exercise of appropriate ? and ? stimulates GH release in young adults
- Magnitude of GH release increased ? with increasing exercise activity
- Older adults have ? exercise-induced GH release
? is a key modifier of exercise-induced GH released
- Individual variation in response to acute ? exercise
GH release is proportional to exercise intensity for both aerobic and resistance exercise
Acute aerobic exercise of appropriate intensity and duration stimulates GH release in young adults
- Magnitude of GH release increased linearly with increasing exercise activity
- Older adults have decreased exercise-induced GH release
Exercise Intensity is a key modifier of exercise-induced GH released
- Individual variation in response to acute aerobic exercise
- Higher in WOMEN because Estrogen → ↑pulses of GH Release
Acute resistance exercise
* When does GH secretion peak?
* How long for GH to return to baseline?
Largest GH response observed with resistance protocols that had high ?, moderate to high ?, ? rest periods
Acute resistance exercise
* Causes a peak in GH secretion at or slightly after the termination of the exercise and returns to baseline levels 90 minutes post-exercise
Largest GH response observed with resistance protocols that had high volume, moderate to high intensity, short rest periods
- Resistance exercise with higher total volume resulted in a greater GH response than resistance exercise with using high loads, lower total volume, long rest periods
- FYI: 20 sets of 1RM (squats) only produced a slight increase in GH, whereas a substantial increase in GH was observed following 10 sets of 10 repetitions with 70% 1RM
Older adults have decreased exercise-induced GH release
Individual variation in response to acute aerobic exercise
Chronic Changes in Resting GH Concentrations
Effect of chronic resistance exercise on resting GH levels?
Chronic Resistance exercise
- No effect on resting GH levels
(Chronic exercise ≠ ↑[GH]resting)
- May be important for tissue remodeling
GH naturally declines with Age
Regulation of Carbohydrate Metabolism during exercise
In skeletal mm fibres ? mediates increases in glucose uptake
In skeletal mm fibres GLUT4 mediates increases in glucose uptake
- upon stimulation with insulin or mm contractions, GLUT4 is translocated from intracellular compartments (vesicles) to the sarcolemma and T-tubules
Skeletal mm is critical in the regulation of glucose homeostasis; major site of whole-body glucose disposal
- GLUT4 is insulin-dependent
Regulation of Carbohydrate Metabolism during exercise
Upon stimulation with ? or ?, GLUT4 is translocated from intracellular compartments (vesicles) to the ? and ?
In skeletal mm fibres GLUT4 mediates increases in glucose uptake
Upon stimulation with insulin or mm contractions, GLUT4 is translocated from intracellular compartments (vesicles) to the sarcolemma and T-tubules
- Distinct signaling mechanisms exist for exercise- and insulin-stimulated glucose transport
- Data shows the combination of maximal insulin stimulus plus a maximal contraction stimulus has additive effects on glucose transport and GLUT4 translocation
Skeletal mm is critical in the regulation of glucose homeostasis; major site of whole-body glucose disposal
- GLUT4 is insulin-dependent
- Skeletal mm and Adipose tissue both have GLUT4
- MM contraction stimulates GLUT4 translocation in skeletal mm only (not in adipose tissue)
Regulation of Carbohydrate Metabolism during exercise
? is critical in the regulation of glucose homeostasis; major site of whole-body glucose disposal
Skeletal mm is critical in the regulation of glucose homeostasis; major site of whole-body glucose disposal
- In skeletal mm fibres GLUT4 mediates increases in glucose uptake
Sk MM Glucose uptake during exercise
What are the two primary determinants of mm glucose uptake during exercise?
Exercise intensity and duration
↑ intensity/duration → ↑ Glucose uptake
Regulation of Plasma [Glucose]
Plasma [glucose] during exercise depends on ? and ?
Plasma [glucose] during exercise depends on glucose uptake by working mm and release from liver (INTENSITY)
- Liver: b/d glycogen to maintain blood [glucose]
4 hormones which increase circulating plasma glucose levels:
(1) Glucagon → ↑ glycogenolysis (liver (no glucagon Receptors on sk mm)) and gluconeogenesis (liver)
(2) Epinephrine → ↑ glycogenolysis (liver + mm) and gluconeogenesis (liver)
(3) Norepinephrine → ↑ glycogenolysis (liver + mm) and gluconeogenesis (liver)
(4) Cortisol → ↑ protein catabolism to release amino acids for gluconeogenesis (liver) = Spare glucose for brain
Regulation of Plasma [Glucose]
4 hormones which increase circulating plasma glucose levels?
4 hormones which increase circulating plasma glucose levels:
(1) Glucagon → ↑ glycogenolysis (liver (no glucagon Receptors on sk mm)) and gluconeogenesis (liver)
(2) Epinephrine → ↑ glycogenolysis (liver + mm) and gluconeogenesis (liver)
(3) Norepinephrine → ↑ glycogenolysis (liver + mm) and gluconeogenesis (liver)
(4) Cortisol → ↑ protein catabolism to release amino acids for gluconeogenesis (liver) = Spare glucose for brain
Plasma [glucose] during exercise depends on glucose uptake by working mm and release from liver (INTENSITY)
- Liver: b/d glycogen to maintain blood [glucose]
Regulation of Plasma [Glucose]
4 hormones which increase circulating plasma glucose levels:
(1) Glucagon → ↑ ? (liver ) and ? (liver)
(2/3) Epinephrine/Norepinephrine → ↑ ? (liver + mm) and ? (liver)
(4) Cortisol → ↑ ? to release amino acids for ? (liver)
4 hormones which increase circulating plasma glucose levels:
(1) Glucagon → ↑ glycogenolysis (liver (no glucagon Receptors on sk mm)) and gluconeogenesis (liver)
(2/3) Epinephrine/Norepinephrine → ↑ glycogenolysis (liver + mm) and gluconeogenesis (liver)
(4) Cortisol → ↑ protein catabolism to release amino acids for gluconeogenesis (liver) = Spare glucose for brain
Plasma [glucose] during exercise depends on glucose uptake by working mm and release from liver (INTENSITY)
- Liver: b/d glycogen to maintain blood [glucose]
Cortisol also Increases FFA availability (separate source for ATP)
Regulation of Plasma [Glucose]
4 hormones which increase circulating plasma glucose levels:
(1) Glucagon → ↑ ? (liver ) and ? (liver)
(2/3) Epinephrine/Norepinephrine → ↑ ? (liver + mm) and ? (liver)
(4) Cortisol → ↑ ? to release amino acids for ? (liver)
4 hormones which increase circulating plasma glucose levels:
(1) Glucagon → ↑ glycogenolysis (liver (no glucagon Receptors on sk mm)) and gluconeogenesis (liver)
(2/3) Epinephrine/Norepinephrine → ↑ glycogenolysis (liver + mm) and gluconeogenesis (liver)
(4) Cortisol → ↑ protein catabolism to release amino acids for gluconeogenesis (liver) = Spare glucose for brain
Plasma [glucose] during exercise depends on glucose uptake by working mm and release from liver (INTENSITY)
- Liver: b/d glycogen to maintain blood [glucose]
Cortisol also Increases FFA availability (separate source for ATP)
Regulation of Plasma [Glucose]
3 hormones (regulate plasma glucose) that increase with onset of exercise?
? Decreases slightly then increases during first 30-45 minutes of exercise
? release by the liver depends on exercise intensity and duration
Glucagon, epinephrine and norepinephrine increase with onset of exercise
Cortisol Decreases slightly then increases during first 30-45 minutes of exercise
Glucose release by the liver depends on exercise intensity and duration
4 hormones which increase circulating plasma glucose levels:
(1) Glucagon → ↑ glycogenolysis (liver (no glucagon Receptors on sk mm)) and gluconeogenesis (liver)
(2/3) Epinephrine/Norepinephrine → ↑ glycogenolysis (liver + mm) and gluconeogenesis (liver)
(4) Cortisol → ↑ protein catabolism to release amino acids for gluconeogenesis (liver) = Spare glucose for brain
Cortisol also Increases FFA availability (separate source for ATP)
Regulation of Plasma Glucose
Describe what is happening to NE and E in the graph: (attached image)
Increased exercise intensity increases ? hormone ? release
Increased exercise intensity increases catecholamine (NE/E) release
- Stimulates glycogenolysis in liver AND muscle
During explosive Short-term exercise:
- mm uses glucose from own glycogen stores before using glucose from liver
- Blood glucose may increase 40-50% above resting values during a sprint as glucose is released from liver at greater rate than taken up by mm
- Following exercise, plasma glucose levels decrease as glucose enters mm to replenish glycogen stores
During prolonged exercise
Relationship between Glucose release and Muscle needs?
During prolonged exercise: rate of glucose release by liver more closely matches the needs of muscle
- Plasma glucose remains at or slightly above resting concentrations and does not decline until late in activity when liver glycogen becomes depleted
Glucagon concentration increases significantly (green on graph)
- Glucagon & Cortisol increase gluconeogenesis
Plasma glucose concentration diuring exercise depends on glucose uptake by working muscles (intensity) and release from liver (via b/d of glycogen)
Glucose/Glycogen Levels During Exercise
Muscle glycogen levels ? as exercise duration increases
Liver glycogen levels will also ? to maintain blood glucose and provide fuel to working muscles
* Glucagon is released from ? → ↑ ? release
* Glucose also increases during
exercise following an increase in
?, ? and
?
Muscle glycogen levels decrease as exercise duration increases
Liver glycogen levels will also decrease to maintain blood glucose and provide fuel to working muscles
* Glucagon is released from pancreas → ↑ liver glucose release
* Glucose also increases during
exercise following an increase in
epinephrine, norepinephrine and
cortisol
Glucose Uptake by Muscles
At rest ? causes GLUT4 to move to the cell surface in ? and ? cells
* GLUT4 moves ? into cells
Insulin concentrations ? during prolonged
exercise
* ? stimulates GLUT4 to surface of cell
* During exercise: increased ? levels and ? uptake by muscle
At rest insulin causes GLUT4 to move to the cell surface in adipocytes and muscle cells
* GLUT4 moves glucose into cells
Insulin concentrations decrease during prolonged
exercise
* Insulin stimulates GLUT4 to surface of cell
* During exercise: increased plasma glucose levels and glucose uptake by muscle
How do muscles take up glucose as insulin levels decrease during exercise?
1. GLUT4 becomes more sensitive to insulin
2. Muscle contraction itself recruits GLUT4 to the muscle cell membrane
* Glucose transported into muscle cell with lower levels of insulin present
Glucose Uptake by Muscles
How do muscles take up glucose as insulin levels decrease during exercise? (2)
- GLUT4 becomes more sensitive to insulin
- Muscle contraction itself recruits GLUT4 to the muscle cell membrane
* Glucose transported into muscle cell with lower levels of insulin present
At rest insulin causes GLUT4 to move to the cell surface in adipocytes and muscle cells
* GLUT4 moves glucose into cells
Insulin concentrations decrease during prolonged
exercise
* Insulin stimulates GLUT4 to surface of cell
* During exercise: increased plasma glucose levels and glucose uptake by muscle
Glucose Uptake by Muscles
How do skeletal muscle contractions increase glucose uptake into active muscles during exercise?
Contraction-induced increase in skeletal muscle glucose uptake during exercise:
Exercise-induced increase in sarcolemmal and t-tubular GLUT4 translocation
* In resting muscle GLUT4 is mainly retained in intracellular vesicle structures
* Imaging studies in mice have shown that insulin as well as muscle contractions translocate GLUT4 to the sarcolemma and t-tubule system
* Content of GLUT4 in the sarcolemma and t-tubules is regulated by the relative efficiency of two processes: endocytosis and exocytosis of GLUT4 containing vesicles
* Contractions/exercise lead to both increased exocytosis and decreased endocytosis
IMAGE SHOWS POTENTIAL SITES OF REGULATION OF MM GLUCOSE UPTAKE DURING EXERCISE
Exercise and Skeletal MM GLUT4 Expression
How does GLUT4 expression differ between the three muscle fibre types?
Type 1 fibres?
The difference in GLUT4 expression between muscle fiber types is small:
* Type I fibers usually have more GLUT4 (20-30%)
* Not observed in all muscles
* Training response restricted to type I fibers recruited in low-intensity training
Exercise effects on GLUT4 Expression
Single bout of exercise: ? increases
* ? increases 3 – 24 hours after exercise (studies are variable)
Exercise training: ? observed but variation in individual responses
Single bout of exercise: GLUT4 mRNA increases
* GLUT4 protein increases 3 – 24 hours after exercise (studies are variable)
Exercise training: increased GLUT4 observed but variation in individual responses
* An increase in skeletal muscle GLUT4 levels is an adaptation to exercise training
Regulation of Fat Metabolism During Exercise
- Free fatty acids (FFA) are a source of energy during ? and during prolonged ? exercise
- FFA are stored as ? in ? tissue and within ?
- When CHO reserves are low (low plasma glucose, low muscle glycogen) ? of fats increases (?)
- Free fatty acids (FFA) are a source of energy during rest and during prolonged endurance exercise
- FFA are stored as triglycerides in adipose tissue and within muscle fibers
- When CHO reserves are low (low plasma glucose, low muscle glycogen) oxidation of fats increases (lipolysis)
Lipolysis:
* TG → FFA + glycerol
* Controlled by: (decreased) insulin, epinephrine, norepinephrine, cortisol, growth hormone
* Major determinant of lipolysis is decreasing insulin
* Cortisol (peaks 30 – 45 mins of exercise), NE/E and growth hormone also contribute to lipolysis
Regulation of Fat Metabolism During Exercise
What is Lipolysis?
What 5 hormones contribute to lipolysis regulation?
Lipolysis:
* TG → FFA + glycerol
* Controlled by: (decreased) insulin, epinephrine, norepinephrine, cortisol, growth hormone
* Major determinant of lipolysis is decreasing insulin
* Cortisol (peaks 30 – 45 mins of exercise), NE/E and growth hormone also contribute to lipolysis
- Free fatty acids (FFA) are a source of energy during rest and during prolonged endurance exercise
- FFA are stored as triglycerides in adipose tissue and within muscle fibers
- When CHO reserves are low (low plasma glucose, low muscle glycogen) oxidation of fats increases (lipolysis)
Hormonal Regulation of Fluid and Electrolytes During Exercise
Three reasons why Plasma Volume Decreases during Exercise
Plasma volume decreases during exercise:
1. Water shifts from plasma volume to interstitial and intracellular spaces due to increases in osmotic pressure from metabolic by-products
2. Increased blood pressure increases hydrostatic pressure
3. Sweating
Prolonged running at ~ 75% VO2max decreases plasma volume 5 – 10%
Adrenal cortex: aldosterone
* Stimuli: ↓ plasma [Na+] and ↓ ECF
* Actions: (kidneys) ↑ plasma [Na+] and ↑ ECF and ↓ plasma [K+]
Hormonal Regulation of Fluid and Electrolytes
Aldosterone:
- Released from:
- Stimulated by:
- Actions:
Aldosterone
* released by Adrenal Cortex
* Stimuli: ↓ plasma [Na+] and ↓ ECF
* Actions: (kidneys) ↑ plasma [Na+] and ↑ ECF and ↓ plasma [K+]
anti-diuretic hormone
* Released From: Posterior Pituitary
* Stimuli: ↑ osmolality and ↓ blood volume
* Actions: ↑ water retention and ↑ vasoconstriction
Hormonal Regulation of Fluid and Electrolytes
Anti-diuretic Hormone (ADH)
- Released from:
- Stimuli:
- Actions:
anti-diuretic hormone
* Released From: Posterior Pituitary
* Stimuli: ↑ osmolality and ↓ blood volume
* Actions: ↑ water retention and ↑ vasoconstriction
Aldosterone
* released by Adrenal Cortex
* Stimuli: ↓ plasma [Na+] and ↓ ECF
* Actions: (kidneys) ↑ plasma [Na+] and ↑ ECF and ↓ plasma [K+]
Hormones involved in Fluid Homeostasis
What two hormones are involved in Fluid Homeostasis?
- Posterior pituitary releases ?
- Adrenal Cortex releases ?
Posterior pituitary: antidiuretic hormone (ADH)
* ↑ during exercise due to ↑ plasma osmolality or ↓ plasma volume
* Due to sweating and fluid shifting from the plasma volume to interstitial and intracellular spaces
* Promotes water retention in the kidney
Adrenal cortex: aldosterone
* Promotes renal reabsorption of Na+, water retention, K+ excretion
Secretion stimulated by:
* ↓ plasma Na+ (from sweating)
* ↓ blood volume (from sweating)
* ↓ blood pressure (from fluid loss)
* ↑ plasma K+
