Homeostasis: Question 4

Worked solution

Part (a): Insulin and its cellular effects

Insulin is secreted by the β (beta) cells of the islets of Langerhans in the pancreas, in response to a rise in blood glucose concentration. Once released into the blood, insulin binds to receptors on the surface of liver, muscle and fat cells and lowers blood glucose concentration in two main ways:

1. It stimulates more glucose transporter proteins to be inserted into the cell-surface membrane of these cells, increasing the rate at which glucose is taken up from the blood.
2. It stimulates glycogenesis. The conversion of excess glucose into glycogen for storage, mainly in liver and muscle cells (insulin also increases the rate at which cells respire glucose, further lowering its blood concentration).

Part (b): The glucagon second-messenger pathway

When blood glucose concentration falls, glucagon is released and binds to a specific receptor on the cell-surface membrane of a liver cell. This is the first messenger, and because glucagon cannot cross the membrane itself, its signal must be relayed inside the cell:

• Binding of glucagon activates a G protein associated with the receptor.
• The activated G protein activates the enzyme adenylyl cyclase.
• Adenylyl cyclase converts ATP into cyclic AMP (cAMP), which acts as the second messenger, diffusing through the cytoplasm to relay the signal.
• cAMP activates protein kinase, which starts an enzyme cascade, each activated enzyme activates many more copies of the next enzyme in the chain, amplifying the original signal enormously.
• The cascade ultimately activates glycogen phosphorylase, the enzyme that catalyses glycogenolysis, the breakdown of glycogen into glucose.

The glucose released by glycogenolysis diffuses out of the liver cell into the blood, raising blood glucose concentration back towards the set point.

Part (c): Detecting glucose in urine with a biosensor test strip

The test strip works through two enzymes acting in sequence:

• Glucose oxidase catalyses the oxidation of glucose (using dissolved oxygen) to gluconic acid, generating hydrogen peroxide as a by-product.
• Peroxidase then catalyses the oxidation of a colourless dye using this hydrogen peroxide, converting it into a coloured product. The more glucose present in the sample, the more hydrogen peroxide is generated, and so the more intense the colour change, allowing the concentration of glucose in the sample to be estimated from the strip.

Glucose does not normally appear in urine at all: although it is small enough to be freely filtered from the blood into the glomerular filtrate, it is almost completely reabsorbed back into the blood in the proximal convoluted tubule. If blood glucose concentration remains too high for long enough, the filtrate arriving at the proximal convoluted tubule contains more glucose than the tubule’s transporter proteins can reabsorb, so some glucose remains in the fluid and is excreted in the urine. Detecting glucose in a urine sample therefore indicates that blood glucose concentration has been persistently too high, i.e. that its control by insulin has not kept it within normal limits.

Final answers

• (a) β cells of the islets of Langerhans secrete insulin, which lowers blood glucose by increasing cellular glucose uptake and by stimulating glycogenesis.
• (b) Glucagon binding activates a G protein and adenylyl cyclase, producing cAMP, which activates protein kinase and an enzyme cascade that activates glycogen phosphorylase, breaking down glycogen to glucose and raising blood glucose concentration.
• (c) Glucose oxidase converts glucose to gluconic acid, releasing hydrogen peroxide; peroxidase uses this hydrogen peroxide to oxidise a dye, producing a colour change proportional to glucose concentration. Glucose appears in urine only once blood glucose concentration is too high for the proximal convoluted tubule to reabsorb it all.