Lesson 16: Homeostasis: Blood Sugar

This lesson covers Theme C/D — homeostasis: blood glucose control (SL and HL), the model example of negative feedback in the whole course. The IB pairs it with diabetes — causes, types and treatment — and HL students meet the wider homeostatic family (thermoregulation, osmoregulation) built on the same loop logic.

The negative feedback loop

Homeostasis keeps internal variables near a set point despite external change. Every loop has the same anatomy: a sensor/receptor detects the variable; a control centre compares it with the set point; effectors act to reverse the change — hence *negative* feedback. Blood glucose is held near ~90 mg per 100 cm³ of blood (≈5 mmol dm⁻³). The sensors and effectors sit together in the islets of Langerhans in the pancreas:

• When glucose rises (after a meal): beta cells secrete insulin. Insulin increases membrane glucose transporters (GLUT4) in muscle and adipose cells, stimulates the liver and muscle to convert glucose to glycogen (glycogenesis), promotes glucose conversion to fat, and increases cellular respiration of glucose. Blood glucose falls.
• When glucose falls (fasting, exercise): alpha cells secrete glucagon. Glucagon acts mainly on the liver, stimulating glycogenolysis (glycogen → glucose) and gluconeogenesis (making glucose from amino acids and glycerol), releasing glucose into the blood.

HL adds adrenaline as a rapid-response hormone: it also raises blood glucose (glycogen breakdown in liver and muscle) as part of the fight-or-flight response. Distinguish the two storage polymers' roles: muscle glycogen is for the muscle's own use (no glucose-6-phosphatase to export glucose); liver glycogen maintains blood glucose for the whole body.

Diabetes: two different failures

Type 1 diabetes is an autoimmune destruction of beta cells, usually beginning in childhood: no insulin is produced. It is treated with insulin injections (or pumps) timed to meals, plus blood-glucose monitoring. Type 2 diabetes is a failure of *response*: insulin is produced but target cells become resistant (receptor/signalling defects), strongly associated with obesity, inactivity, genetic predisposition and age; it is managed first by diet, exercise and weight loss, with drugs (e.g. metformin) and sometimes insulin later. Complications of chronic hyperglycaemia examiners mention: damage to small blood vessels — retinopathy (blindness), nephropathy (kidney failure), neuropathy, and increased cardiovascular disease. Hypoglycaemia (overdose of insulin, missed meals) is acutely dangerous because the brain depends on blood glucose: sweating, tremor, confusion, potentially coma — while hyperglycaemia acts slowly. Glucose tolerance tests are the diagnostic data format: a glucose load is given and blood glucose is tracked over two hours; in diabetics the curve rises higher and returns to baseline much more slowly. Worked reading: a healthy curve peaks at ~140 mg/100 cm³ at 30 min and is back under 100 by 120 min; a type 2 curve peaks above 200 and remains above 140 at 120 min — interpret by comparing peak height *and* clearance rate, not by a single value.

The wider homeostatic family (HL awareness)

The same loop architecture controls temperature (hypothalamus, sweating/shivering/vasomotor responses), water potential of blood (ADH from the pituitary acting on kidney collecting ducts — Lesson 2's aquaporins), blood pH and CO₂ (ventilation control), and blood calcium. Examiners combine them: a question may describe a novel variable and ask you to *deduce* the loop from first principles. The transferable skill is naming sensor, control centre, effector and the direction of correction for any system given.

Nature of Science / TOK link

The discovery of insulin (Banting, Best, Macleod and Collip, Toronto 1921–22) converted a fatal diagnosis into a manageable condition within a year — and produced one of science's famous priority disputes, revisited when the Nobel went to Banting and Macleod only. TOK: credit in science is socially allocated; the knowledge (insulin lowers blood glucose) and the recognition of who found it are different kinds of claims. Modern insulin is made by genetically modified bacteria using the human gene — possible only because the genetic code is universal (Lesson 7).

Common mistakes (from examiner reports)

• Swapping insulin and glucagon sources/actions, or writing "insulin converts glucose to glycogen" without naming target tissues.
• Saying insulin is taken orally by type 1 diabetics (it is a protein — it would be digested; it is injected).
• Describing type 2 as "no insulin produced" (it is resistance to insulin; production may be normal or high initially).
• Calling feedback "positive" when it corrects a change.

IB Exam Experience

Paper 1 style. 1. Glucagon is secreted by… A. beta cells when glucose is high B. alpha cells when glucose is low C. the liver D. the adrenal medulla 2. Insulin lowers blood glucose by… A. stimulating glycogen breakdown in the liver B. increasing glucose uptake by muscle and fat cells and stimulating glycogenesis C. converting glucose to glucagon D. stopping all respiration 3. Type 2 diabetes is primarily a problem of… A. autoimmune destruction of beta cells B. target cells responding poorly to insulin C. excess glucagon secretion only D. kidney failure Answer key. 1 — B. 2 — B. 3 — B. Paper 2 style. Two hours after a glucose drink, a subject's blood glucose is 165 mg/100 cm³, having peaked at 205 mg/100 cm³. A healthy reference peaks at 135 and returns below 100 by 120 minutes. (a) Evaluate whether the subject's response suggests diabetes. [2] (b) Explain the role of insulin in lowering blood glucose after a meal. [3] (c) Distinguish between the causes of type 1 and type 2 diabetes. [2] *Marking notes.* (a) Peak is higher and clearance much slower than reference — glucose still elevated at 2 h [1]; pattern is consistent with (type 2) diabetes/insulin resistance [1]. (b) Insulin released from beta cells [1]; increases glucose uptake by muscle/adipose (GLUT4 insertion) [1]; stimulates glycogenesis in liver and muscle and conversion to fat [1]. (c) Type 1: autoimmune destruction of insulin-secreting beta cells [1]; type 2: target-cell insulin resistance (with risk factors obesity/genetics) [1]. IA idea. Simulate glucose tolerance analysis using published datasets, or investigate a homeostatic variable you can measure ethically: heart-rate/skin-temperature recovery after mild exercise or hand immersion in cold water, modelling the feedback response curve.

Extended case study: continuous glucose monitors and the data turn in diabetes care

Modern type 1 management increasingly runs on continuous glucose monitors (CGMs) — a filament sensor under the skin sampling interstitial glucose every few minutes, feeding pumps that adjust insulin semi-automatically ("hybrid closed loops"). The IB-relevant biology is unchanged — sensor, control centre, effector — but the loop is now partly silicon: the human sets targets and meal announcements; the algorithm handles minute-to-minute corrections. Data from such systems reframe the glucose tolerance curve of the main lesson as a *time-in-range* distribution: patients aim for >70% of readings between 3.9 and 10 mmol dm⁻³, and the same data show why single HbA1c values (a 3-month average glycation marker) hide dangerous variability. For evaluation questions, this is fertile ground: technology improves control but adds cost, alarm fatigue and a digital divide — equity arguments (Lesson: who gets the sensors?) echo the stem-cell banking discussion. Mechanistically, also note the sensor measures interstitial fluid glucose, lagging blood values by ~5–10 minutes — measurement is always of a proxy, a miniature TOK point.

Thermoregulation: the same loop, different effectors (HL transfer)

The examiners' favourite transfer test is to ask about temperature with the glucose machinery as template. Sensor and control centre: thermoreceptors in skin and in the hypothalamus itself. Cooling responses: vasoconstriction of skin arterioles (less warm blood at the surface), shivering (involuntary muscle contraction generating heat), piloerection (minor in humans), and behavioural change; warming responses: vasodilation, sweating (evaporative cooling — Lesson 5's latent heat), reduced metabolic rate. Fever is not a failure of the loop but a *raised set point*: pyrogens reset the hypothalamic thermostat, so the body deliberately heats itself (shivering during the "chill" phase) to a level hostile to pathogens — which is why antipyretics (lowering the set point) produce sweating as the body dumps the now-excess heat. If you can narrate fever correctly as a set-point change rather than broken control, you understand negative feedback; if a question describes any new variable, borrow this skeleton sentence by sentence.

One more application: the kidney–glucose connection and modern type 2 drugs

One of the newest classes of type 2 diabetes drugs, the SGLT2 inhibitors ("gliflozins"), works nowhere near the pancreas: they block the sodium–glucose co-transporter in the kidney's proximal tubule (Lesson 2's co-transport, Lesson 25's nephron), so glucose that would have been reabsorbed is excreted in urine — typically 60–80 g of glucose per day, lowering blood glucose without insulin and, as trials showed, protecting the heart and kidneys as a bonus. Understanding the drug requires the whole course in miniature: membrane transport, nephron function, feedback (blood glucose falls without forcing insulin), and evaluation (side effects follow the mechanism — glucose in urine raises urinary-tract infection risk). When an exam describes an unfamiliar drug, locate its target in a system you know and reason forwards, exactly as here; novel contexts are old mechanisms wearing new names.

Examiner's lens: final drills (homeostasis)

• The two-hormone table, finalised: insulin — beta cells, released when glucose is high, increases uptake and glycogenesis, net effect lowers glucose; glucagon — alpha cells, released when glucose is low, stimulates glycogenolysis and gluconeogenesis in the liver, net effect raises glucose. Adrenaline backs up glucagon in emergencies.
• Negative feedback phrasing: always close the loop in answers — state the change, the correction, and that the correction removes the original stimulus ("…so insulin secretion falls as glucose returns to the set point").
• Glucose tolerance curves: judge by shape (peak height and return-to-baseline time), and remember the test uses a standard 75 g glucose load after fasting — protocol details earn the first mark in data questions.
• Self-test: a type 1 diabetic injects insulin but skips lunch. Predict and explain the risk (hypoglycaemia — insulin drives uptake and storage while no glucose is arriving; the brain is first affected).