11) Hormonal Control of Metabolism During Exercise Flashcards

Question

# 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 **?**

Answer 1

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** ## Footnote 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)

Answer 2

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) ## Footnote 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**

Answer 3

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

Answer 4

Breaking down of mm fibers

Answer 5

Muscle Atrophy - Driven by greater **cortisol** binding (vs testosterone (anabolic) binding on skeletal mm ## Footnote Breaking down of mm fibers Cortisol and Testosterone are antagonists

Answer 6

↑ Testosterone binding to skeletal MM blocks the genetic element on DNA that binds cortisol → prevent cortisol binding → prevent atrophy ## Footnote Muscle Atrophy = Breaking down of mm fibers - Driven by greater **cortisol** binding (vs testosterone (anabolic) binding on skeletal mm Cortisol and Testosterone are antagonists

Answer 7

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 ## Footnote Muscle Atrophy = Breaking down of mm fibers - Driven by greater **cortisol** binding (vs testosterone (anabolic) binding on skeletal mm Cortisol and Testosterone are antagonists

Answer 8

Cortisol release following resistance exercise may improve mm cell remodeling by removing damaged proteins - help with recovery Then testosterone and GH induce hypertrophy ## Footnote 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

Answer 9

Growth hormone: - Released from **anterior pituitary** - Release stimulated by **GHRH** from **hypothalamus** ## Footnote 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)

Answer 10

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 ## Footnote *Sleep* and *exercise* are strongest stimuli Growth hormone: - Released from **anterior pituitary** - Release stimulated by **GHRH** from **hypothalamus**

Answer 11

Effects of GH may be mediated by **insulin-like growth factors (IGFs) from liver** | GHRH - Growth hormone releasing hormone ## Footnote *Sleep* and *exercise* are strongest stimuli Growth hormone: - Released from **anterior pituitary** - Release stimulated by **GHRH** from **hypothalamus**

Answer 12

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 ## Footnote *Sleep* and *exercise* are strongest stimuli Growth hormone: - Released from **anterior pituitary** - Release stimulated by **GHRH** from **hypothalamus**

Answer 13

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 ## Footnote 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

Answer 14

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 ## Footnote 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

Answer 15

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 ## Footnote 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

Answer 16

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 ## Footnote 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

Answer 17

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 ## Footnote 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

Answer 18

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 ## Footnote - Higher in WOMEN because Estrogen → ↑pulses of GH Release

Answer 19

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 ## Footnote * 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

Answer 20

Chronic Resistance exercise - **No effect** on *resting* GH levels (Chronic exercise ≠ ↑[GH]resting) - May be important for tissue remodeling ## Footnote GH naturally declines with Age

Answer 21

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 ## Footnote **Skeletal mm** is critical in the regulation of glucose homeostasis; major site of whole-body glucose disposal - GLUT4 is **insulin-dependent**

Answer 22

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 ## Footnote **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)

Answer 23

**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

Answer 24

Exercise **intensity** and **duration** ↑ intensity/duration → ↑ Glucose uptake

Answer 25

Plasma [glucose] during exercise depends on **glucose uptake by working mm** and **release from liver** (INTENSITY) - Liver: b/d glycogen to maintain blood [glucose] ## Footnote 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

Answer 26

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 ## Footnote Plasma [glucose] during exercise depends on **glucose uptake by working mm** and **release from liver** (INTENSITY) - Liver: b/d glycogen to maintain blood [glucose]

Answer 27

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 ## Footnote 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)

Answer 28

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 ## Footnote 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)

Answer 29

**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* ## Footnote 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)

Answer 30

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

Answer 31

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** ## Footnote Plasma glucose concentration diuring exercise depends on glucose uptake by working muscles (intensity) and release from **liver** (via b/d of glycogen)

Answer 32

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**

Answer 33

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 ## Footnote 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

Answer 34

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 ## Footnote 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

Answer 35

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** ## Footnote IMAGE SHOWS POTENTIAL SITES OF REGULATION OF MM GLUCOSE UPTAKE DURING EXERCISE

Answer 36

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*

Answer 37

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

Answer 38

* 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) ## Footnote 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

Answer 39

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 ## Footnote * 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)

Answer 40

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** ## Footnote 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+]

Answer 41

*Aldosterone* * released by **Adrenal Cortex** * Stimuli: **↓ plasma [Na+] and ↓ ECF** * Actions: **(kidneys) ↑ plasma [Na+]** and **↑ ECF and ↓ plasma [K+]** ## Footnote **anti-diuretic hormone** * Released From: Posterior Pituitary * Stimuli: ↑ osmolality and ↓ blood volume * Actions: ↑ water retention and ↑ vasoconstriction

Answer 42

*anti-diuretic hormone* * Released From: **Posterior Pituitary** * Stimuli: **↑ osmolality** and **↓ blood volume** * Actions: **↑ water retention** and **↑ vasoconstriction** ## Footnote *Aldosterone* * released by **Adrenal Cortex** * Stimuli: **↓ plasma [Na+] and ↓ ECF** * Actions: **(kidneys) ↑ plasma [Na+]** and **↑ ECF and ↓ plasma [K+]**

Answer 43

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+**

11) ****Hormonal Control of Metabolism During Exercise**** Flashcards

11) Hormonal Control of Metabolism During Exercise Flashcards