Blood Glucose Control

Blood glucose is one of the most tightly regulated variables in the body. A typical healthy adult maintains a fasting blood glucose of about 4–5.5 mmol dm⁻³, rising to around 7–8 mmol dm⁻³ after a carbohydrate meal. Too low and the brain fails (hypoglycaemia, unconsciousness, death). Too high and tissues are damaged by glycation (hyperglycaemia, diabetes complications). This lesson follows the cellular and molecular events that keep glucose in range, as required by OCR A-Level Biology A specification 5.1.4(g)–(i).

Key Definitions:

• Glycogenesis — the synthesis of glycogen from glucose (stimulated by insulin).
• Glycogenolysis — the breakdown of glycogen to glucose (stimulated by glucagon and adrenaline).
• Gluconeogenesis — the synthesis of glucose from non-carbohydrate sources (e.g. amino acids, glycerol, lactate), also stimulated by glucagon and cortisol.
• Insulin — protein hormone from β cells of the pancreas; lowers blood glucose.
• Glucagon — peptide hormone from α cells of the pancreas; raises blood glucose.

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The Big Picture — Negative Feedback

Blood glucose control is a classic example of negative feedback: a deviation from the set point triggers a response that opposes the deviation.

• If blood glucose rises, β cells release insulin → cells take up glucose, glycogenesis occurs, blood glucose falls back.
• If blood glucose falls, α cells release glucagon → glycogenolysis and gluconeogenesis in the liver, blood glucose rises back.

flowchart TB
    NORM[Normal blood glucose 4-5.5 mmol/dm3]
    NORM -->|Rises after meal| HIGH[High blood glucose]
    HIGH --> BC[β cells release insulin]
    BC --> G1[Cells take up glucose<br/>Glycogenesis in liver and muscle]
    G1 --> NORM
    NORM -->|Falls during fasting/exercise| LOW[Low blood glucose]
    LOW --> AC[α cells release glucagon]
    AC --> G2[Glycogenolysis<br/>Gluconeogenesis in liver]
    G2 --> NORM

Two hormones, acting in opposite directions, give very precise control. This is better than a single hormone because the body can adjust glucose both up and down.

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What Happens When Blood Glucose Rises

After a meal, glucose is absorbed from the ileum into the hepatic portal vein and flows straight to the liver and pancreas.

1. β Cells Detect the Rise

β cells in the islets of Langerhans have a beautiful molecular mechanism for glucose sensing — OCR expects you to know it in detail.

1. Glucose enters the β cell via a GLUT2 transporter (facilitated diffusion).
2. Inside, glucose is metabolised by glycolysis and the Krebs cycle, generating ATP.
3. Rising ATP/ADP ratio closes ATP-sensitive K⁺ channels on the β cell membrane.
4. K⁺ stops leaving the cell, so the membrane depolarises.
5. Depolarisation opens voltage-gated Ca²⁺ channels.
6. Ca²⁺ enters the β cell, triggering vesicles containing insulin to fuse with the membrane.
7. Insulin is released by exocytosis into the blood.

This mechanism is a perfect example of how hormones and cell biology overlap: it is essentially the same as synaptic transmission, with K⁺ channels closing instead of voltage-gated channels opening. You should be able to describe every step for full exam marks.

2. Insulin Acts on Target Cells

Insulin binds to insulin receptors (tyrosine kinase receptors) on the surface of liver, muscle and adipose cells. This triggers several effects:

• Increases glucose uptake — in muscle and fat, insulin causes GLUT4 transporter vesicles to fuse with the plasma membrane, dramatically increasing the number of glucose channels. The liver already has GLUT2 transporters so does not need this, but glucose uptake increases anyway because insulin activates glucokinase, trapping glucose inside the cell.
• Stimulates glycogenesis — glucose molecules are joined into glycogen for storage by glycogen synthase.
• Inhibits glycogenolysis — glycogen breakdown stops.
• Inhibits gluconeogenesis — the liver stops making new glucose.
• Stimulates lipogenesis — in adipose tissue, excess glucose is converted to triglycerides.
• Stimulates protein synthesis — insulin is an anabolic hormone.

The net result: glucose leaves the blood and enters cells, where it is either used (respiration) or stored (glycogen, fat). Blood glucose returns to normal.

3. Negative Feedback Completes the Loop

As blood glucose falls, less glucose enters the β cells, ATP levels fall, K⁺ channels reopen, the membrane repolarises and insulin secretion decreases.

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What Happens When Blood Glucose Falls

During fasting, exercise or overnight, glucose demand exceeds supply and blood glucose begins to fall.

1. α Cells Detect the Fall

α cells are less well characterised than β cells, but they release glucagon in response to low glucose. (Somewhat counterintuitively, α cells also depolarise when glucose is low — the opposite of β cells.)

2. Glucagon Acts on the Liver