One gene, two tissues: the biology of GLP-1
GLP-1 comes from the same gene as glucagon, lasts about two minutes in the blood, and was re-engineered to last a week.
Transcript and sources
- Your gut and your pancreas read the same gene, and make signals that do opposite jobs.
- The gene makes one long chain, called proglucagon, a hundred and eighty building blocks long.
- In the pancreas, the chain is cut to release glucagon, which raises blood sugar between meals.
- In the gut, the same chain is cut in different places. Out comes GLP-1, and its sibling, GLP-2.
- GLP-1 and its partner GIP are why a meal releases more insulin than the same sugar given straight into a vein. Scientists call this the incretin effect.
- But natural GLP-1 lasts only about two minutes. An enzyme called DPP-4 snips it, and the kidneys clear the rest.
- So chemists rebuilt it: one swapped building block to dodge the enzyme, and a fatty tail that grips a blood protein. Two minutes became a week.
- One gene, cut two ways, and rebuilt by chemists, became today's GLP-1 medicines.
- See how every GLP-1 medicine compares, at peplexicon.com.
Sources
- UniProt P01275: Pro-glucagon (human), processed peptides
- Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007
- Nauck M et al. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986
- Deacon CF et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus. Diabetes. 1995
- Ozempic (semaglutide) prescribing information, DailyMed