Hormonal Control of Substrate Mobilization and Metabolism During Exercise

Comprehensive vocabulary flashcards covering the hormonal and metabolic regulation of substrate mobilization, blood glucose homeostasis, and training adaptations during exercise.

Reactive hypoglycemia

A condition resulting in a marked drop in blood glucose that develops during $30\text{ minutes}$ of exercise at $75\%\,\dot{V}O_2\text{ max}$ when carbohydrate (glucose) is ingested $45\text{ minutes}$ prior to the start of exercise.

Dual control of muscle glycogenolysis

The parallel regulation of muscle glycogen breakdown to glucose mediated simultaneously by the epinephrine-cyclic $\text{AMP}$ pathway and the intracellular $\text{Ca}^{2+}\text{-calmodulin}$ pathway.

$$\text{Ca}^{2+}\text{-calmodulin}$$

An intracellular regulatory complex activated by the release of $\text{Ca}^{2+}$ from the sarcoplasmic reticulum during muscle contraction that stimulates glycogen breakdown, ensuring fuel mobilization matches contractile activity even during adrenergic blockade.

Propranolol

A $\beta\text{-adrenergic}$ receptor blocker used experimentally to demonstrate that muscle glycogenolysis still proceeds during exercise due to activation of the $\text{Ca}^{2+}\text{-calmodulin}$ mechanism.

Four processes of blood glucose homeostasis

The primary mechanisms maintaining plasma glucose during exercise: mobilization of glucose from liver glycogen stores, mobilization of free fatty acids ($\text{FFAs}$) from adipose tissue to spare glucose, gluconeogenesis in the liver from amino acids, lactic acid, and glycerol, and blocking glucose entry into non-working cells.

Cortisol

A slow-acting steroid hormone that mobilizes $\text{FFAs}$ from adipose tissue, accelerates liver gluconeogenesis, and reduces peripheral glucose utilization; plasma levels decrease during low-intensity exercise but rise significantly at intensities exceeding approximately $60\%\,\dot{V}O_2\text{ max}$.

Growth hormone (GH)

A slow-acting hormone that supports cortisol by decreasing tissue glucose uptake, increasing $\text{FFA}$ mobilization, and stimulating gluconeogenesis; its plasma concentration increases with exercise intensity and demonstrates a greater response in trained runners compared to untrained controls.

Thyroid hormones ($\text{thyroxine}$ and $\text{T}_3$)

Hormones that act in a permissive manner to allow other hormones to exert their full metabolic effects during exercise, showing little concentration change with exercise intensity and only small increases with training.

Insulin

A fast-acting pancreatic hormone that facilitates glucose and $\text{FFA}$ uptake and storage; its plasma concentration decreases during exercise (reaching a minimum around $60\%\,\dot{V}O_2\text{ max}$) to prevent hypoglycemia and allow substrate mobilization, with trained individuals exhibiting a smaller decline.

Glucagon

A fast-acting pancreatic hormone that mobilizes glucose from liver glycogen and stimulates adipose lipolysis; plasma concentrations rise during prolonged exercise in untrained individuals but show little to no change in endurance-trained individuals.

Catecholamines (Epinephrine and Norepinephrine)

Fast-acting hormones that stimulate liver and muscle glycogen breakdown, enhance adipose lipolysis, and block cellular glucose entry; plasma levels rise progressively with exercise intensity and duration, but show a significantly reduced response after endurance training.

GLUT4 (Glucose transporter 4)

Glucose transporter proteins translocated to the muscle cell membrane in response to elevated intracellular $\text{Ca}^{2+}$ and mechanical stimuli, enabling muscle glucose uptake to increase $7\text{ to }20$ times faster during exercise despite suppressed circulating insulin levels.

Hormonal response to exercise training

An adaptive attenuation across endocrine systems characterized by blunted exercise-induced changes in plasma epinephrine, norepinephrine, glucagon, cortisol, and insulin at the same absolute workload and at equivalent relative intensities ($\%\,\dot{V}O_2\text{ max}$).

Increases with exercise and duration

Epinephrine, Norepinephrine, cortisol and glucagon

Decrease in response to exercise and longer duration

Insulin

Why does NOE go up more than EPI with the same receptors?

NOE is spill over from sympathetic nerve endings and cardiovascular regulation. EPI is more metabolic focus, glycogen metabolism in muscle and lipolysis.

How do catecholamines respond to training adaptation?

Start to decrease. Metabolic and cardiovascular workload stress is lessened with training. Take high intensity for epic and norepinephrine to increase.

What delivery of fuel (glucose) parallels the activation of contraction?

In exercise, glycogen breakdown to glucose in muscle is under dual control of epinephrine-cyclic AMP (can stimulate glycogen breakdown) and Ca+2-calmodulin (lower intensity) (from the sarcoplasmic reticulum, triggers muscle contraction) (releases) glycogen phosphorylase (fast and precise). The delivery of fuel (glucose) parallels the activation of contraction.

Changes in muscle glycogen before and after Propranolol administration

• Under these conditions, blocking epi and norepi didn't affect glycogen utilization (low intensity exercise)

  • Shows other mechanisms breaking down glycogen, (internal mechanisms) primarily calcium release

How to test if hormone is affected by pharmacological use?

use antagonist (block) or agonists (enhances effects) to affect receptors and then compare to without drugs

Calcium release (in muscle contraction) is stimulator of?

glycogen breakdown

Primary processes hormones affect external mechanism:

glucose, fatty acid, glycogen metabolism

Blood glucose for the brain and other tissues, not muscle

Brain can't use FFA or amino acids, mainly blood glucose

#1 way to increase blood glucose

Mobilization of glucose from liver glycogen stores, dumped into blood (liver glycogenolysis)

Plasma glucose maintained through 4 processes:

1. Mobilization of glucose from liver glycogen stores, dumped into blood (liver glycogenolysis) #1 way to increase blood glucose

2. Mobilization of FFA from adipose tissue, the more is taken up by muscle to spare glucose

   1. Spares blood glucose

3. Gluconeogenesis from AA, lactic acid and glycerol

4. Blocking (reducing) the entry of glucose into cells (to prevent from dropping blood glucose)

   1. Forces use of FFA as a fuel by muscle

5. Controlled by hormones

   1. Permissive or slow-acting (cortisol, released slowly, protein synthesis takes awhile and takes awhile to create affects) GH

   2. Fast-acting (catecholamines release fast)

Cortisol Effects Metabolically:

• Increases in response to exercise and duration

• Slow-acting hormone

• Effects:

  • Stimulate FFA metabolization from adipose tissue (lipolysis) to be taken up in muscle

  • Enhance gluconeogenesis in the liver

    • Catabolic - breaks down proteins to provide AA to liver for gluconeogenesis

  • Decrease the rate of blood glucose utilization by cells (maintain blood glucose as FFA metabolism is increased)

• Effects of exercise

  • Decrease during low-intensity exercise

  • Increase during high-intensity exercise

    • Above ~60% VO2 max

Growth Hormone Effects Metabolically:

• Slow acting hormone, sooner than cortisol

• Effects

  • Supports the action of cortisol

    • Decreases glucose uptake by tissues

    • Increases FFA metabolism

    • Enhances gluconeogenesis

• Exercise effect

  • Increase in plasma GH with increased intensity and duration

  • GREATER response in trained runners (other hormones decreased with training)

Fast Acting Hormones

Insulin:

• Uptake and storage of glucose and FFA  in the muscle; anabolic

  • Don’t want to store when exercising

• Plasma concentration decreases during exercise

• Decreased insulin response following training

 

Glucagon: catabolic (mobilizing glucose)

• Mobilization of glucose and FFA fuels, catabolic

• Plasma concentration increases during exercise

• Decreased response following training

-Insulin and glucagon secretion influenced by catecholamines and the sympathetic nervous system  during exercise, as well as plasma glucose concentration (humoral effect)

2 ways glucose is monitored

catecholamines (inhibit and stimulate glucagon) and blood glucose concentration

Catecholamines and Insulin and Glucagon

Interactions of all 3:

• During exercise blood glucose is being maintained

• Catecholamines under most exercise conditions, is the primary controller of insulin and glucagon

  • When E/NE are released --> decreases/inhibits insulin

    • Stimulates  glucagon

Ca stimulate internal mechanisms? Does pH (higher acidity) cause what? Speed of enzyme activity?

muscle contraction

increase H+

more rapid and precise in relation to muscle activity

Glycogenolysis is related to exercise…?

intensity (glycogen break down)

high intensity exercise results in WHAT and WHAT glycogen depletion?

great and more rapid

glycogenesis

synthesis of glycogen

Powerful stimulator of glycogenolysis (break down of glycogen)

plasma epinephrine

First source of energy

ATP

Break down to replace ATP

creatine phosphate

10-30 seconds energy

glycolysis

end product of glycogen break down

lactic acid build up

aerobic for long duration exercise

oxidative glycolysis and FFA used