HomeostasisRegulation of Blood Glucose

Homeostasis

• Animals possess a nervous system and a hormonal system that interact in order to maintain the constancy of the internal environment.

• Nervous system – rapid communication• Hormonal System – slower communication

• Both systems use chemical messengers.• Hormonal system – hormones• Nervous system – neurotransmitters at the synapse.

Regulation of Blood Glucose Levels

• An example of different hormones interacting in order to achieve balance.

• If too little – cells cannot respire effectively• If too much – water potential of blood lowered and can

cause osmotic problems and dehydration.

• Lots of cells can utilise fatty acids as a source of energy in respiration BUT brain cells and rbcs can only use GLUCOSE.

Hormones

• Produced by endocrine glands and secreted directly into blood stream.

• Carried in blood plasma to the cells on which they act (target cells).

• Target cells have receptors on their cell-surface membrane that are a complementary shape to the hormone.

• Effective in small quantities. Have widespread and long-lasting effects

Blood Glucose

• Blood glucose is normally set at around 90mg per 100cm3 of blood.

• Some glucose needs to be circulating in the blood at all times as cells will need a constant supply for respiration.

• Too much or too little can cause problems

How glucose enters the blood

• Absorption from the gut following digestion of carbohydrates

• Breakdown of stored glycogen (Glycogenolysis)

• Conversion of non-carbohydrates such as lactate, fats and amino acids (Gluconeogenesis)

Control

• Hormones regulate the levels of glucose in the blood via a negative feedback system.

E.g.• Excess glucose in the blood after a carbohydrate

rich meal needs to be got rid of.Or• Extra glucose needs to be released rapidly from

glycogen stores when muscles are depleting glucose concentration during exercise.

When Blood Glucose Levels Rise

• Detected by beta cells (β-cells) in the pancreas.• Beta cells are situated in little groups of cells

inside the pancreas called islets of Langerhans.• Beta cells make insulin (B-IN)• [Pancreas is mostly made up of cells that

secrete digestive enzymes (lipase, amylase, protease)]

When Blood Glucose Levels Rise

• When blood with high conc. of glucose reaches the islets, glucose is absorbed into the beta cells.

• Plasma membrane of a β cell contains carrier proteins that transport glucose into cells by facilitated diffusion.

• This stimulates vesicles of insulin to move to the membrane and release the insulin into the capillaries.

When Blood Glucose Levels Rise

• Insulin circulates around body in bloodstream.

• Insulin attaches to glycoprotein receptors on the cell-surface membrane of most body cell but has largest effect on muscle tissue, adipose tissue and in the liver.

• When insulin attaches to the receptors of these cells, it stimulates the active uptake of glucose into these cells.

How does insulin work?

• It changes the tertiary structure of glucose transport protein channels in muscle and fat cells, causing them to change shape and open up, allowing more glucose into the cells.

• Causes an increase in the number of carrier proteins in cell-surface membrane of muscle and adipose cells.

• Activates enzymes that convert glucose into glycogen (in liver and muscle cells) – maintains steep diffusion gradient – so more glucose enters liver cell.(GLYCOGENESIS)

• In adipose cells, glucose is turned into fatty acids and glycerol and stored as fat.

• Overall result is a decrease in blood glucose concentration.

Effect of insulin on the glucose permeability of cells

Insulin binds toreceptors on cell

surface membranes

intracellularchemical

signal

signal triggers the fusion of carrier-containing

vesicles with the surface membrane

The additional carriers increase glucose

permeability

glucose carrier forfacilitated diffusion

plasmamembrane

Lowering Glucose Levels

• More glucose enters muscle cells, more will be used up in respiration.

• More glucose enters adipose cells, more will be turned into fat.

• More glucose is stored as glycogen in the liver and muscles a (glycogenesis).

• YouTube - Insulin, Glucose and You

What Happens When Blood Glucose Levels Fall?

• If concentration of blood glucose drops to below 90mg per 100cm3, insulin secretion stops.

• Low glucose levels are detected by alpha cells (α-cells) in islets of Langerhans.

• These then secrete the hormone glucagon into blood plasma.

• Only cells in liver have the receptors that bind to glucagon, so only those cells respond.

Effects of Glucagon

• Activates enzymes that breakdown stored glycogen into glucose

• Activates enzymes that convert substances (other than carbohydrates) into glucose (i.e proteins/amino acids)

• Called gluconeogenesis (making new glucose from substances)

• Glucose levels in blood stream RISE.

FINE CONTROL

• Most of the time, both insulin and glucagon are secreted into the bloodstream with proportions adjusted when necessary to maintain glucose concentrations at a fairly constant level.

glucose glycogenglycogen glucosenon-carbohydrates glucose

detected by the alpha cells

detected by the beta cells

glucagon secretion insulin secretion

release of fatty acids from

adipose tissue

uptake of glucose for fatty acid synthesis

increased permeability of body

cells to glucose

Dual Hormonal Control achieves

Glucose Homeostasis

Role of Adrenaline

• Adrenaline – can also increase blood glucose levels.

• At times of excitement or stress, adrenaline is produced by the adrenal glands (above kidneys)

• Adrenaline raises blood glucose levels by:- Activating an enzyme that causes breakdown of

glycogen to glucose in the liver (Glycogenolysis)- Inactivating an enzyme that synthesises

glycogen from glucose.

Second Messenger Model

• Adrenaline and Glucagon work together to raise glucose levels.• Adrenaline and Glucagon are the first messengers• They bind to receptors on cell-surface membrane of target

cells in liver (Hormone-Receptor Complex).• This complex activates a G-protein on inside of plasma

membrane of target cell which activates an enzyme (adenyl cyclase).

• This enzyme acts on ATP, removing 2 of the phosphate groups, making cyclic adenosine monophosphate (cAMP).

• cAMP activates other enzymes that carry out breakdown of glycogen to glucose.

• cAMP is the second messenger• Advantage – one molecule of adrenaline produces many

molecules of cAMP that inturn activates large amounts of enzyme which produces lots of product. (CASCADE EFFECT).

Hormone binds tosurface receptor

Binding induces a change in the shape of the receptor, which

activates a G-protein located on the inner surface of the membrane

The G-protein activates the enzyme

adenyl cyclase

Adenyl cyclase converts ATP into

cyclic AMP

Cyclic AMP(second messenger)

cAMP activates enzymes required for specific biochemical reactions

inactive enzyme active enzymeActivated enzymes

produce specific changes in the cell

Hormone -induced change

Hormone Action and Amplification

When a protein hormone binds to its cell-surface receptor, a cascade of events is triggered with one

event leading inevitably to another

Each molecule within the cascade system activates many molecules of the next stage, such that there is

an amplification of the original message triggered by the hormone

A single molecule of hormone promotes the synthesis of thousands of the molecules of the final product

G-protein Adenyl cyclase

Each activated receptor protein activates many

molecules of adenyl cyclaseEach activated adenyl cyclase

molecule converts many molecules of ATPinto cyclic AMP

Each cyclic AMP molecule activates many copies of the

desired enzymeEach enzyme molecule

catalyses the formation of many molecules of product

The binding of one hormone molecule at the cell surface promotes

the synthesis of thousands of cyclic AMP molecules (amplification); a

small concentration of hormone in the blood produces a massive response within the target cell

Glucagon binds tosurface receptor

Many molecules of adenyl cyclase are activated, each of which converts many molecules of ATP into cyclic AMP

Many molecules of Cyclic AMP

cAMP activates many copies of the enzyme that splits glycogen into glucose

inactive enzyme active enzymeA phosphorylase

enzyme catalyses the conversion of glycogen

into glucose

Glucose enters the bloodstream