Chapter 11 — Quiz
Twenty-two questions.
Multiple choice
1. Insulin consists of:
a) one chain of 51 residues b) two chains of 21 and 30 residues joined by disulfide bonds
c) three chains d) 191 residues
2. The insulin receptor is:
a) a GPCR b) a receptor tyrosine kinase c) an ion channel d) a nuclear receptor
3. Insulin causes glucose uptake principally by:
a) breaking down glucose b) moving GLUT4 transporters to the cell surface c) blocking glucagon
d) increasing renal excretion
4. Injected insulin causes hypoglycemia because:
a) it is impure b) the dose cannot be withdrawn when glucose falls, so counter-regulation pushes
against a fixed input c) it stimulates glucagon d) it is glucose-dependent
5. Hypoglycemia unawareness refers to:
a) patients not knowing about the risk b) loss of the warning symptoms of low blood glucose
c) inaccurate glucose meters d) asymptomatic high glucose
6. In type 1 diabetes, insulin therapy is:
a) an override of resistance b) a replacement of an absent hormone c) optional d) a surrogate
7. Insulin therapy in type 1 diabetes over decades:
a) develops tolerance b) requires escalating doses indefinitely c) does not lose effectiveness
d) causes receptor downregulation
8. The reason for answer 7 is that:
a) insulin is very potent b) there is no intact system being overridden — nothing adapts
c) the dose is titrated d) analogs prevent tolerance
9. Recombinant human insulin was approved in:
a) 1922 b) 1955 c) 1982 d) 2005
10. Insulin hexamers are:
a) the active form b) inactive, and must dissociate before the molecule can act c) a manufacturing
impurity d) formed only in the bloodstream
11. Rapid-acting analogs work by:
a) increasing potency b) substitutions that discourage hexamer formation c) adding a fatty acid
d) protamine complexing
12. Insulin detemir uses:
a) an isoelectric shift b) a fatty acid for albumin binding c) protamine d) multihexamer chains
13. Which other drug in this book uses the same albumin-binding strategy?
a) exenatide b) semaglutide c) metformin d) tirzepatide only
14. Animal-sourced insulin's principal drawbacks included:
a) it did not work b) supply tied to meat production, variable purity, and immunogenicity from
sequence differences c) excessive potency d) oral administration
15. Closed-loop systems are described as "artificial pancreas" — an overstatement because:
a) they are not automated b) they modulate insulin only and have no glucagon arm c) they are
investigational d) they require injections
16. "Smart insulin" would:
a) connect to a phone b) be glucose-responsive, restoring the glucose-dependence insulin lacks
c) last longer d) be taken orally
17. The 1923 patent was sold for one dollar. A complication to the simple pricing story is:
a) the patent was never granted b) that patent covered the 1923 product, not modern analogs
c) insulin is cheap in the U.S. d) there were no later patents
Short answer
18. Explain why insulin required no randomized trial, and state the general principle.
19. Explain the two-lever argument for why injected insulin cannot self-correct.
20. State the override-versus-replace rule and apply it to insulin and to GLP-1 agonists.
Applying the rating discipline
21. The analog rating is split — ✅ for one population, ⚠️ for another. Explain why, and name the
rule.
22. This chapter rates a device-and-algorithm system ✅. Is that a legitimate use of a peptide
book's rating system?
Answer key
**1.** b. **2.** b. **3.** b. **4.** b. **5.** b. **6.** b. **7.** c. **8.** b. **9.** c. **10.** b.
**11.** b. **12.** b. **13.** b. **14.** b. **15.** b. **16.** b. **17.** b.
**18.** Insulin reversed a **uniformly fatal** condition, reproducibly, in patient after patient. The
alternative explanations that randomization exists to exclude — natural history, expectation, chance,
regression to the mean — were **not available**, because untreated type 1 diabetes did not remit.
**The general principle: the strength of evidence required scales with the plausibility of alternative
explanations.** For insulin in 1922 there were none. For essentially everything else in this book there
are several, which is why Chapter 5 exists. A field reasoning from insulin to "we don't need trials"
would be catastrophically wrong.
**19.** Normal physiology has **two levers**: when glucose falls, beta cells stop releasing insulin
**and** alpha cells release glucagon. Both act to restore glucose. **Injected insulin removes the first
lever** — the dose is already administered and cannot be withdrawn. Counter-regulation still operates,
but it is now pushing against a fixed input it cannot influence, so glucose may keep falling. This is
Chapter 3's counter-regulation argument in its sharpest form, and it is why hypoglycemia is unavoidable
in principle rather than merely a dosing failure.
**20.** **The rule:** expect tolerance and reversal when a therapy **overrides an intact regulated
system**; expect durability when it **replaces an absent one.**
**Insulin in type 1:** the beta cells are destroyed. There is no intact system to override, no feedback
loop measuring exogenous insulin, no set point being defended. Nothing adapts, so the therapy does not
lose effect over decades.
**GLP-1 agonists for weight:** appetite regulation is intact and defending a set point. The drug
outweighs it while present; the set point was never removed. Stop, and the intact system resumes and
weight returns.
**One rule, opposite outcomes, and it predicts both** — which is what makes it worth carrying into
Part III, where several compounds are marketed as replacements and are in fact overrides.
**21.** The claim "analogs are better than human insulin" is a **molecule-level** claim, and the
evidence differs by population. In **type 1 diabetes**, the pharmacokinetic advantages translate into
reduced nocturnal and severe hypoglycemia, which is well supported — **✅**. In **type 2 diabetes**, the
incremental benefit over human insulin is smaller and has been genuinely contested — **⚠️** — and this
matters because the cost difference is large.
**The rule is rule 6: one molecule, many ratings.** A single verdict on "analogs" would either overstate
the type 2 evidence or understate the type 1 evidence, and there is no wording that avoids both.
**22.** Yes, and deliberately.
The rating system attaches to **claims about outcomes**, not to molecule types. "Automated insulin
delivery systems improve glycemic control and reduce hypoglycemia in type 1 diabetes" is a claim about
an outcome in a population, tested by randomized trials, and it can be rated by exactly the same
criteria as any drug claim.
**More importantly, excluding it would distort the picture.** The most significant progress in insulin
therapy over the past two decades has been in **delivery and control** rather than in molecules. A book
that rated only peptides would report that insulin has barely changed since the analogs — which is false
in the way that matters to a patient. Chapter 4 argued that the delivery system is part of the drug;
this rating is that argument applied consistently.