Homeostasis Regulation 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 to receptors on cell surface membranes intracellular chemical signal signal triggers the fusion of carrier-containing vesicles with the surface membrane The additional carriers increase glucose permeability glucose carrier for facilitated diffusion plasma membrane

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  glycogen glycogen  glucose non-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 to surface 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 enzyme Activated 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-proteinAdenyl cyclase Each activated receptor protein activates many molecules of adenyl cyclase Each activated adenyl cyclase molecule converts many molecules of ATP into cyclic AMP Each cyclic AMP molecule activates many copies of the desired enzyme Each 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 to surface 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 enzyme A phosphorylase enzyme catalyses the conversion of glycogen into glucose Glucose enters the bloodstream