Diabetes — AQA A-level Biology

SPEC 3.6.4.2 - RESPONSES — HOMEOSTASIS

Adrenaline, Second Messenger & Diabetes

How adrenaline raises blood glucose via cAMP · The second messenger model · Type I vs Type II diabetes · Required Practical 11

Building on Lesson 6.07

In Lesson 6.07 you learned that insulin and glucagon are the main hormones regulating blood glucose. This lesson adds a third hormone — adrenaline — and examines how hormones whose molecules are too large to enter cells can still control intracellular enzymes via the second messenger model.

This Lesson Covers

Adrenaline — source, trigger, and target action

The second messenger model: adenylate cyclase → cAMP → protein kinase

Signal amplification

Type I and Type II diabetes — causes, comparison, and management

Evaluating the role of the food industry in Type II diabetes

Required Practical 11 — colorimetric glucose measurement

Exam Importance

The second messenger model and diabetes comparison are among the most frequently examined topics on Paper 2. Expect mechanism questions worth 4–6 marks and evaluation questions worth 3–4 marks on the food industry / health debate.

Adrenaline

Definition

Adrenaline is a hormone secreted by the adrenal medulla (inner region of the adrenal glands, located above the kidneys) in response to stress, fear, or low blood glucose concentration. It prepares the body for the "fight or flight" response.

Adrenaline is a catecholamine — a small, polar molecule derived from the amino acid tyrosine. Because it is polar (hydrophilic), it cannot pass through the hydrophobic core of the phospholipid bilayer of the cell surface membrane.

Adrenaline's Action on Blood Glucose

Binds to receptor proteins on the surface membranes of target cells (e.g. liver and muscle cells)

Activates enzymes involved in the conversion of glycogen to glucose (glycogenolysis)

Increases blood glucose concentration rapidly — providing fuel for muscle activity

Examiner Alert

⚠️ Do not say adrenaline "enters the cell" or "directly activates glycogen phosphorylase". It binds a receptor on the cell surface membrane only. The intracellular cascade is driven by the second messenger cAMP.

Why a Second Messenger?

Glucagon is a large polypeptide (29 amino acids) and adrenaline is a small but polar (hydrophilic) molecule. Neither can pass through the hydrophobic core of the phospholipid bilayer, yet both need to stimulate intracellular enzyme activity. The solution: a second messenger system.

First Messenger

The hormone (adrenaline or glucagon) — acts outside the cell by binding its receptor on the cell surface membrane.

Second Messenger

Cyclic AMP (cAMP) — produced inside the cell; relays the signal to activate intracellular enzymes.

Signal Amplification

One hormone molecule binding one receptor → activates many adenylate cyclase molecules → produces thousands of cAMP molecules → activates thousands of protein kinase molecules → activates thousands of glycogen phosphorylase molecules. The signal is amplified enormously at each step.

The Second Messenger Model

The full sequence when adrenaline or glucagon binds to a liver cell:

1

Hormone binds receptor — adrenaline/glucagon binds to a complementary receptor protein on the cell surface membrane (specific binding — lock and key).

2

Adenylate cyclase activated — hormone-receptor binding causes a conformational change that activates the membrane-bound enzyme adenylate cyclase.

3

ATP → cAMP — adenylate cyclase catalyses the conversion of ATP to cyclic AMP (cAMP) inside the cell. cAMP is the second messenger.

4

Protein kinase A activated — cAMP binds to and activates protein kinase A (PKA).

5

Glycogen phosphorylase activated — protein kinase A phosphorylates (adds a phosphate group to) inactive glycogen phosphorylase, converting it to the active form.

6

Glycogenolysis — active glycogen phosphorylase catalyses the breakdown of glycogen → glucose-1-phosphate → glucose, which is released into the blood.

Second Messenger Model — Diagram

Adrenaline/glucagon cannot cross the bilayer — cAMP carries the signal inside the cell.

DEEP Chain — Second Messenger Model

Use this structure for any 4–6 mark question asking you to explain how adrenaline or glucagon raises blood glucose:

DDefine: The second messenger model describes how hormones that cannot cross the cell surface membrane (e.g. adrenaline, glucagon) relay signals inside the cell via a second messenger molecule (cAMP).

EExplain mechanism: Adrenaline binds its receptor on the cell surface membrane → activates adenylate cyclase → catalyses ATP → cAMP → cAMP activates protein kinase A → protein kinase A phosphorylates and activates glycogen phosphorylase → glycogenolysis: glycogen → glucose → blood glucose rises.

EEvidence: Adenylate cyclase is a membrane-bound enzyme; cAMP is a small, water-soluble molecule produced inside the cell — confirmed by biochemical studies. Signal amplification: one hormone molecule can generate thousands of cAMP molecules.

PPractical/Quantitative: If adenylate cyclase is inhibited experimentally, adrenaline cannot raise intracellular cAMP and glycogenolysis does not occur — confirming cAMP is essential to the pathway.

Practice Question

Adrenaline is released during exercise. Describe and explain how adrenaline increases blood glucose concentration in liver cells, referring to the second messenger model. [5 marks]

D:

Adrenaline is a hormone released from the adrenal medulla; it cannot cross the cell surface membrane so acts via a second messenger (cAMP).

E:

Adrenaline binds complementary receptor proteins on the cell surface membrane of liver cells → receptor-ligand complex activates the membrane-bound enzyme adenylate cyclase → adenylate cyclase catalyses the conversion of ATP to cyclic AMP (cAMP) inside the cell.

E:

cAMP activates protein kinase A → protein kinase A phosphorylates glycogen phosphorylase (converting it to its active form) → glycogen phosphorylase catalyses glycogenolysis: glycogen is broken down to glucose-1-phosphate → glucose → released into the blood, raising blood glucose concentration.

P:

Signal is amplified — one adrenaline molecule can activate many adenylate cyclase molecules → many cAMP molecules → many protein kinase molecules → a large increase in glycogenolysis rate. (1 mark for any reference to amplification.)

Type I Diabetes

Definition

Type I diabetes is an autoimmune condition in which the body's immune system attacks and destroys the β cells of the islets of Langerhans in the pancreas, resulting in little or no insulin production. Blood glucose cannot be regulated normally.

Cause & Mechanism

Immune system destroys β cells → insufficient insulin produced

After a meal, blood glucose rises but no insulin is secreted to stimulate glucose uptake or glycogenesis

Blood glucose remains abnormally high (hyperglycaemia)

Glucose may appear in urine (glycosuria) as it exceeds the reabsorption threshold in the kidney

Control

Insulin replacement therapy — regular subcutaneous injections or an insulin pump

Carbohydrate monitoring to match insulin dose to dietary intake

Usually diagnosed in childhood or early adulthood

Type II Diabetes

Definition

Type II diabetes is a condition in which target cells become less sensitive to insulin (insulin resistance), so cells do not take up glucose effectively even when insulin is present. It may also involve reduced insulin secretion in later stages.

Cause & Mechanism

Target cells (liver, muscle, adipose) have fewer or less responsive insulin receptors

Glucose uptake is impaired → blood glucose remains elevated after meals

Initially, β cells compensate by producing more insulin, but may eventually become exhausted

Strongly associated with obesity, physical inactivity, and age; genetic factors also contribute

Control

Dietary modification — reduced refined sugar and total carbohydrate intake

Increased physical activity — exercise improves insulin sensitivity

Oral hypoglycaemic drugs (e.g. metformin — reduces hepatic glucose output)

Insulin therapy in advanced cases

Type I vs Type II Diabetes

FeatureType IType II

CauseAutoimmune destruction of β cellsInsulin resistance of target cells; may involve reduced secretion

Insulin productionLittle or noneNormal or gradually reduced

Age of onsetTypically childhood / young adultTypically middle age / adult (increasing in younger people)

Body weight linkNot linked to obesityStrongly associated with obesity

Onset speedRapidGradual

Primary treatmentInsulin replacement (injection/pump)Diet, exercise, oral hypoglycaemics

Insulin therapyAlways requiredMay be needed in advanced cases

Proportion of cases~10%~90%

Examiner Alert

⚠️ A very common error: "Type I = body does not respond to insulin" — this is Type II. Type I = β cells are destroyed → insufficient insulin is produced. Always state the correct mechanism for each type.

Evaluating the Type II Debate

The AQA specification requires you to evaluate the positions of health advisers and the food industry in relation to the increased incidence of Type II diabetes.

Health Advisers' Position

High sugar and refined carbohydrate diets contribute to obesity → insulin resistance

Ultra-processed foods are marketed aggressively, particularly to children

Labelling reforms (traffic light system), sugar taxes, and advertising restrictions are necessary public health measures

Physical inactivity compounds dietary risk — structural changes needed (e.g. active travel)

Food Industry's Position

No single food causes diabetes — overall dietary pattern and lifestyle are responsible

Industry has reduced sugar, salt and fat in many products voluntarily

Personal choice and responsibility: individuals decide what to eat

Correlation between sugar intake and diabetes does not prove causation

Evaluation Tip

AQA evaluation questions expect you to acknowledge both sides, then reach a justified conclusion using biological evidence. E.g. "The epidemiological data linking obesity to Type II diabetes is robust, suggesting dietary factors are significant — however, genetic predisposition and physical activity also contribute, so regulatory interventions alone may be insufficient."

Required Practical 11

RP 11: Production of a dilution series of a glucose solution and use of colorimetric techniques to produce a calibration curve with which to identify the concentration of glucose in an unknown 'urine' sample.

IV: Known glucose concentration (mg cm⁻³ or mmol dm⁻³)

DV: Absorbance (or percentage transmission) measured by a colorimeter

Control variables:

Volume of Benedict's reagent added — same volume ensures consistent reaction conditions

Temperature and time of heating — same conditions ensure comparable colour development

Volume of glucose/urine sample used — ensures fair comparison

pH — same buffer or reagent batch; pH affects enzyme/reagent reaction rate

RP 11 — Calibration Curve & Interpretation

After heating each known concentration with Benedict's solution and centrifuging (or allowing precipitate to form), the coloured supernatant is measured in a colorimeter:

1

Prepare a dilution series of glucose from a stock solution (e.g. 0, 1, 2, 4, 6, 8, 10 mg cm⁻³). Record volumes of stock and distilled water used for each concentration.

2

Add equal volumes of Benedict's reagent to each tube. Heat at 80°C in a water bath for the same duration (e.g. 5 min). A precipitate forms — the more glucose, the more orange/brick-red precipitate.

3

Cool tubes and measure absorbance of the blue supernatant at 620 nm (red filter). Higher glucose → less blue remaining → lower absorbance.

4

Plot a calibration curve: absorbance (y-axis) vs glucose concentration (x-axis). Draw a line of best fit.

5

Measure the absorbance of the unknown 'urine' sample in the same way. Read off glucose concentration from the calibration curve using the line of best fit.

Examiner Alert

⚠️ The calibration curve is used to identify concentration from absorbance — not to prove the urine sample is from a diabetic. Always read off the curve using the line of best fit; do not extrapolate beyond the range of standards.

Examiner Alerts & Synoptic Links

Common Errors

cAMP is not ATP — cAMP is cyclic adenosine monophosphate, produced FROM ATP by adenylate cyclase. Do not write "cAMP = energy source."

Adrenaline does not enter the cell — it binds the receptor on the outer membrane surface only.

Protein kinase activates glycogen phosphorylase by phosphorylation — not by "releasing" it or "switching it on."

Type II is insulin resistance, not insulin absence — insulin is still produced (initially); the problem is the target cell response.

RP 11 — do not confuse high glucose with high absorbance: more glucose → more precipitate → less blue remaining → LOWER absorbance of supernatant.

Synoptic Link

Link to enzyme inhibition (Topic 1.05): If adenylate cyclase is inhibited (e.g. by a competitive inhibitor), the second messenger cascade cannot proceed — a question might ask you to predict the effect on blood glucose regulation. The principle is the same as enzyme inhibition: reduced enzyme activity → reduced product (cAMP) → downstream effects blocked.

Link to cell signalling (Topics 2.04 & 6.05): Receptor proteins on cell surfaces are involved in hormone action (6.08), synaptic transmission (ACh binding, 6.05), and immune recognition (antigens, Topic 2.06) — all use complementary binding.

Summary

Key Points — Lesson 6.08

TopicCore Fact

Adrenaline sourceSecreted by adrenal medulla; released in stress / low blood glucose

Adrenaline actionBinds receptor on cell surface membrane → activates glycogenolysis via second messenger

Second messengercAMP — produced from ATP by adenylate cyclase inside the cell

CascadeHormone → adenylate cyclase → cAMP → protein kinase A → glycogen phosphorylase → glycogenolysis

AmplificationEach step multiplies signal — one hormone molecule → large rise in blood glucose

Type I diabetesAutoimmune destruction of β cells → no insulin → managed with insulin injections

Type II diabetesInsulin resistance of target cells → linked to obesity → managed with diet/exercise/oral drugs

RP 11Dilution series + Benedict's + colorimeter → calibration curve → find unknown glucose concentration

Exam Tip

For the second messenger mechanism: name every molecule in the correct order — adenylate cyclase, cAMP, protein kinase, glycogen phosphorylase. Each named molecule at the correct step earns marks. For diabetes questions: always state the mechanism (β cell destruction vs insulin resistance) not just the outcome.