5.4.3 Controlling Blood Glucose Concentration

Factors affecting blood glucose concentration

• There are three ways in which glucose can enter the bloodstream:
  • Absorption in the gut following carbohydrate digestion
  • Hydrolysis of glycogen stores
  • Non-carbohydrates such as lipids, lactate and amino acids that have been converted to glucose

• The amount of glucose that gets absorbed into the blood from the products of digestion can vary substantially
  • Some meals may be much more carbohydrate-rich than others

• Control systems within the body help to manage the concentration of glucose in the blood via the hormones insulin and glucagon
• When there is excess glucose in the blood from a carbohydrate-dense meal it is removed
  • This occurs through increased glucose uptake into muscle, fat and liver cells and glycogenesis

• When there is insufficient glucose in the blood for metabolic needs it is rapidly released from storage molecules
  • This occurs through glycogenolysis and gluconeogenesis

• The levels of insulin and glucagon present in the blood are constantly regulated and adjusted in order to maintain the blood glucose concentration at a mostly constant level

The control of blood glucose concentration

• If the concentration of glucose in the blood decreases below a certain level, cells may not have enough glucose for respiration and may not be able to function normally
• If the concentration of glucose in the blood increases above a certain level, this can also disrupt the normal function of cells, potentially causing major problems
• The control of blood glucose concentration is a key part of homeostasis
• Blood glucose concentration is controlled by two hormones secreted by endocrine tissue in the pancreas
• This tissue is made up of groups of cells known as the islets of Langerhans
• The islets of Langerhans contain two cell types:
  • α cells that secrete the hormone glucagon
  • β cells that secrete the hormone insulin

• These α and β cells act as the receptors and initiate the response for controlling blood glucose concentration
• The control of blood glucose concentration by glucagon can be used to demonstrate the principles of cell signalling

Decrease in blood glucose concentration

• If a decrease in blood glucose concentration occurs, it is detected by the α and β cells in the pancreas:
  • The α cells respond by secreting glucagon
  • The β cells respond by stopping the secretion of insulin

• The decrease in blood insulin concentration reduces the use of glucose by liver and muscle cells
• Glucagon binds to receptors in the cell surface membranes of liver cells
• This binding causes a conformational change in the receptor protein that activates a G protein
• This activated G protein activates the enzyme adenylyl cyclase
• Active adenylyl cyclase catalyses the conversion of ATP to the second messenger, cyclic AMP (cAMP)
• cAMP binds to protein kinase A enzymes, activating them
• Active protein kinase A enzymes activate phosphorylase kinase enzymes by adding phosphate groups to them
• Active phosphorylase kinase enzymes activate glycogen phosphorylase enzymes
• Active glycogen phosphorylase enzymes catalyse the breakdown of glycogen to glucose
  • This process is known as glycogenolysis

• The enzyme cascade described above amplifies the original signal from glucagon and results in the releasing of extra glucose by the liver to increase the blood glucose concentration back to a normal level

The effect of glucagon released by pancreatic α cells when a decrease in blood glucose concentration is detected

• The hormone adrenaline also increases the concentration of blood glucose
• It does this by binding to different receptors on the surface of liver cells that activate the same enzyme cascade and lead to the same end result – the breakdown of glycogen by glycogen phosphorylase
• Adrenaline also stimulates the breakdown of glycogen stores in muscle during exercise
• The glucose produced remains in the muscle cells where it is needed for respiration

Increase in blood glucose concentration

• When the blood glucose concentration increases to above the normal range it is detected by the β cells in the pancreas
• When the concentration of glucose is high glucose molecules enter the β cells by facilitated diffusion
• The cells respire this glucose and produce ATP
• High concentrations of ATP causes the potassium channels in the β cells to close, producing a change in the membrane potential
• This change in the membrane potential causes the voltage-gated calcium channels to open
• In response to the influx of calcium ions, the β cells secrete the hormone insulin
  • Insulin-containing vesicles move towards the cell-surface membrane where they release insulin into the capillaries

• Once in the bloodstream, insulin circulates around the body
• It stimulates the uptake of glucose by muscles cells, fat cells and the liver

Action of insulin

• Muscle cells, fat storage cells, adipose tissue and liver cells possess glucose transporter proteins in their surface membranes
  • They are the target cells of insulin

• These membrane proteins allow for the uptake of glucose molecules via facilitated diffusion
  • The rate of glucose uptake for these cells is limited by the number of glucose transporter proteins present

• The glucose transporter proteins on target cells are insulin-sensitive
• Insulin binds to specific receptors on the membranes of target cells
  • This stimulates them to activate/add more glucose transporter proteins to their cell surface membrane which increases the permeability of the cells to glucose
  • As a result, the rate of facilitated diffusion increases

As the number of glucose transporter proteins in the membrane increases the permeability of the cell to glucose increases

• Insulin also helps to increase the uptake of glucose in the liver by stimulating glycogenesis
  • Once glucose has entered a liver cell an enzyme rapidly converts it to glucose phosphate
  • Different enzymes then convert glucose phosphate into glycogen
  • This helps to lower glucose concentration within the liver cell
  • A steep diffusion gradient is maintained between the blood in the capillaries and the liver cells

Negative feedback control

• Blood glucose concentration is regulated by negative feedback control mechanisms
• In negative feedback systems:
  • Receptors detect whether a specific level is too low or too high
  • This information is communicated through the hormonal or nervous system to effectors
  • Effectors react to counteract the change by bringing the level back to normal

• In the control of blood glucose concentration:
  • α and β cells in the pancreas act as the receptors
  • They release the hormones glucagon (secreted by α cells) and insulin (secreted by β cells)
  • Liver cells act as the effectors in response to glucagon and liver, muscle and fat cells act as the effectors in response to insulin

How negative feedback control mechanisms regulate blood glucose concentration

The role of the liver

• The liver plays a vital role in the conversion between glycogen and glucose
  • The conversion between these molecules helps to regulate blood glucose concentration

• Both insulin and glucagon have specific receptors on the membranes of liver cells
• When these hormones bind to their receptors they trigger several processes within the liver
• Glycogenesis
  • Glycgogenesis is the synthesis of glycogen from glucose molecules
  • Insulin triggers this process after it detects an increased blood glucose concentration
  • The synthesis of glycogen removes glucose molecules from the bloodstream and decreases the blood glucose concentration to within a normal range
  • Glycogen acts as a compact and efficient carbohydrate storage molecule

•  Glycogenolysis
  • Glycogenolysis is the breakdown of glycogen to produce glucose molecules
  • Glucagon triggers this process after it detects a decreased blood glucose concentration
  • It activates enzymes within the liver that breakdown glycogen molecules into glucose
  • The breakdown of glycogen releases more glucose molecules to the bloodstream and increases the blood glucose concentration to within the normal range

•  Gluconeogenesis
  • Gluconeogenesis is the synthesis of glucose molecules from non-carbohydrate molecules
  • Glucagon also triggers this by activating enzymes within the liver
  • These enzymes convert other molecules, such as fatty acids and amino acids, into glucose molecules
  • Glucose molecules are released into the bloodstream which increases the blood glucose concentration to within the normal range