4 - Hormonal regulation of fuel homeostasis

what are the two systems that control blood glucose and fuel metabolism?

1. Endocrine – pancreatic hormones (insulin, glucagon), cortisol, growth hormone, thyroid hormones, others

2. Sympathetic nervous system

what are the most important hormones controlling fuel balance? (2 hormone)

Insulin and glucagon

where are these hormones made?

They are made in the islets of Langerhans in the pancreas.

• β cells → insulin

• α cells → glucagon

what happens when you eat and your blood glucose increases?

stimulates insulin release + and inhibits glucagon

what effect does this have?

• Insulin targets liver, muscle and fat → to take up, use and store glucose (anabolic)

what processes increase due to this?

• ↑ glucose oxidation, ↑ glycogen synthesis, ↑ fat synthesis, ↑ protein synthesis

what does insulin do in target tissues?

increases anabolic processes.

what are these processes?

• more glucose is taken up by muscles + adipose tissue = by adding more glucose transporters

• more glucose taken up by the liver = by increasing glucokinase activity

• increases production of glycogen in liver + muscles = by activating glycogen synthase

• Promotes synthesis of fatty acids + α-glycerophosphate → which combine into TAG for storage in adipose tissue

• causes lipoprotein lipase production by fat cells, which free fatty acids from blood lipoproteins so they can be stored as fat.

what else does insulin do in target tissues?

decreases catabolic processes.

how?

• inhibits glycogen phosphorylase = less glycogenolysis in liver + muscle cells

• inhibits gluconeogenesis in liver

• inhibits ketone production in liver

• Inhibits lipolysis by ↓ intracellular lipase activity in adipose tissue

why does insulin Inhibits ketone production?

ketones are a backup fuel for when glucose is scarce. Insulin means glucose is available, so ketones aren’t needed.

why does insulin Inhibits lipolysis?

after a meal, fat should be stored, not broken down, so insulin switches off hormone-sensitive lipase.

what happens in fasted (postabsorptive) state?

the blood glucose concentration drops, glucagon is released and insulin is inhibited.

where does glucagon mainly target?

the liver.

what does it cause the liver to do?

• increase glycogenolysis

• increase gluconeogenesis

• increase ketogenesis

what do these processes do?

glycogenolysis = breaks down stored glycogen into glucose

gluconeogenesis = makes new glucose from non-carbohydrates such as lactate, glycerol and amino acids

ketogenesis = makes ketones from fatty acids as a backup fuel when glucose is low

what is cortisol and where is it made?

it is a steroid stress hormone made by the adrenal cortex.

what does it do?

Maintains the liver and adipose enzymes needed for gluconeogenesis and lipolysis.

what ios lypolysis?

it is the break down of stored triglycerides in fat cells into fatty acids and glycerol, which are released into the blood for energy.

what is a disease caused by the production of too little cortisol + what is it?

Addison's disease - body can't produce the normal postabsorptive response

what is a disease caused by the production of too much cortisol + what is it?

Cushing's syndrome - triggers postabsorptive changes and opposes insulin when not needed.

what is GH + where is it made + what is controlled by?

growth hormone is made by the anterior pituitary and is controlled by the hypothalamus in the brain.

what does GH do in regards to insulin?

opposes the metabolic effects of insulin.

how?

• Makes adipose more sensitive to lipolytic stimuli = ↑ fat breakdown

• ↑ gluconeogenesis in liver

• ↓ insulin's ability to promote glucose uptake in peripheral tissues

what are thyroid hormones + where are they made?

T3/T4 are Iodinated tyrosine derivatives made in thyroid follicles.

what is their main role?

set the basal set basal metabolic rate in most tissues.

how?

• ↑ mitochondrial oxidative phosphorylation → regulate fuel use

• ↑ plasma membrane Na⁺/K⁺ ATPase activity

• Regulate expression of many metabolic enzymes (gene regulation)

what is the overall effect of cortisol and GH on the body?

they are both anti-insulin – they push the body towards releasing fuel.

what triggers neuronal control of blood glucose levels + how is it detected?

decrease in plasma glucose is detected by glucose receptors in the CNS.

what is afferent and efferent?

afferent - carries signal in from stimulus to CNS.

efferent - carries signal out from CNS to effector.

when plasma glucose drops, the efferent response splits into 2 pathways, what are they?

1. hormonal = adrenal medulla releases adrenaline into bloodstream

2. neural = sympathetic nerves directly stimulate liver, adipose tissue + pancreatic islets.

what are the effects of these pathways on the islets?

causes them to inhibit insulin + stimulate glucagon.

what are the effects of these pathways on the liver?

causes liver to increase glycogenolysis + gluconeogenesis to increase plasma glucose.

what are the effects of these pathways on adipose tissue?

causes them to increase lipolysis (the breakdown of stored fat aka. triglycerides into: Free fatty acids + Glycerol, which can then be used as an energy source.

what are the effects of the neural pathway on skeletal muscle?

increases glycogenolysis.

why does the other pathway not work on skeletal muscle?

because muscles have no sympathetic innervation.

what is the end result of all of these things?

increases plasma’s glucose, fatty acids + glycerol.

how does the body respond to prolonged fasting/starvation? - immediate response?

glucose sparing takes place - where peripheral tissues use fatty acids + ketones and save glucose for the CNS (same as postabsorptive state)

what is the short-term effect?

muscle protein is broken down into amino acids and the liver turns them into glucose via the keto acid pathway.

what is the long-term effect (3-4 days)?

the brain adapts to use ketones as well as glucose.

why does the brain adapt to use ketones as well as glucose?

as ketones are made mainly of fatty acids released from TAG, so less protein breakdown is needed and less muscle is wasted.

how efficient is this?

very as blood glucose falls by only a few % after 4 days and only ~25% after 1 month.

how does the body respond to exercise?

similar to fasting to release fuel for activity.

what do the contracting muscles require?

large amounts of fuel.

what happens to the amounts of insulin and glucagon?

insulin falls + glucagon rises.

what makes these hormones increase/decrease?

• decrease in blood glucose

• increase in circulating adrenaline

• increase in sympathetic discharge in the islets of langerhans

whta does adrenaline + sympathetic activity do in the liver, fat + muscles?

increase catabolism!

what is catabolism?

The breakdown of complex molecules into simpler molecules to release energy or produce substances the body can use.