Meet the hormones.
What GLP-1, GIP and related hormones do, and why metabolic therapies target their signals.
Hormones are chemical messages. Receptors are the proteins that receive them. These five signals help explain the targets you’ll see in the metabolic trial explorers.
Incretins are the gut’s meal-time signal to the pancreas. GLP-1 and GIP help it release insulin, which lowers blood glucose, when glucose is elevated. Glucagon, amylin and calcitonin are related targets, but are not incretins.
“Mimic” describes a signal, not an identical molecule. An agonist activates a receptor; an antagonist blocks it. Some therapies activate several receptors, while others combine activation with blocking. Drugs can be modified to last longer than the body’s own hormones.
GLP-1
Glucagon-like peptide-1
Made mainly in L cells lining the intestine.
Its everyday job
After eating, it helps the pancreas release insulin when glucose is high and limits glucagon release. It also slows stomach emptying and contributes to fullness.
Why therapies target it
Medicines activate its receptor to extend signals involved in blood-glucose regulation and appetite.
Natural GLP-1 is broken down within minutes; long-acting receptor drugs are engineered medicines with different exposure.
Backbone trace · one bead per amino acid.
N and C mark the two ends of the chain.
About this structure
Native human GLP-1(7–36)-amide. Model 1 of 20. Trifluoroethanol/water solution, pH 2.5, 300 K. One experimentally restrained NMR conformation of the 30-residue active GLP-1 form. Solvent can stabilize helicity; this is not a fixed shape in blood.
These flexible peptides can take other shapes. The trace shows one experimental conformation, with side chains and any binding partners omitted. Each view is scaled to fit.
PDB 1D0R · Solution NMRGIP
Glucose-dependent insulinotropic polypeptide
Made mainly in K cells in the upper small intestine.
Its everyday job
It helps the pancreas release insulin after eating when glucose is elevated. Its effect on glucagon also depends on the glucose level.
Why therapies target it
Its role in meal-related glucose control makes it a drug target, often alongside GLP-1.
Some medicines activate the GIP receptor; other experimental approaches block it. Those are distinct mechanisms.
Backbone trace · one bead per amino acid.
N and C mark the two ends of the chain.
About this structure
Native human GIP(1–42). Model 1 of 20. 50% trifluoroethanol / 50% water, pH 3.0, 298 K. One experimentally restrained NMR conformation of full-length GIP. This solvent promotes helicity; circulating GIP is flexible.
These flexible peptides can take other shapes. The trace shows one experimental conformation, with side chains and any binding partners omitted. Each view is scaled to fit.
PDB 2OBU · Solution NMRGlucagon
Made mainly in Alpha cells in the pancreas.
Its everyday job
It tells the liver to release glucose, helping keep fuel available between meals and when blood glucose falls. It also helps the liver handle fats and amino acids.
Why therapies target it
Researchers combine glucagon-receptor activity with other pathways to investigate effects on energy use and metabolism.
Glucagon raises blood glucose; increased energy expenditure during glucagon infusion does not establish the same effect for ordinary natural secretion.
Backbone trace · one bead per amino acid.
N and C mark the two ends of the chain.
About this structure
Native human glucagon(1–29). Glucagon bound to human glucagon receptor in an active Gs complex. Only the complete native glucagon peptide is extracted. Receptor, G protein and nanobody are hidden. The displayed conformation is receptor-bound; 3.7 Å is the reported global map resolution.
These flexible peptides can take other shapes. The trace shows one experimental conformation, with side chains and any binding partners omitted. Each view is scaled to fit.
PDB 6LMK · Cryo-electron microscopyAmylin
Islet amyloid polypeptide (IAPP)
Made mainly in Insulin-producing beta cells in the pancreas.
Its everyday job
Released alongside insulin after meals, it slows stomach emptying, limits the meal-related rise in glucagon, and helps signal fullness.
Why therapies target it
Drug developers use longer-lasting amylin-like signals to study appetite and meal-related glucose control.
Amylin is not an incretin, and amylin-targeting medicines differ in how selectively they activate related receptors.
Backbone trace · one bead per amino acid.
N and C mark the two ends of the chain.
About this structure
Native human amylin(1–37)-amide. Model 1 of 20. SDS detergent micelles (200 mM SDS), pH 7.3, 298 K. One experimentally restrained conformation in a membrane-mimicking detergent. The native Cys2–Cys7 disulfide and terminal amidation are present. This is a micelle-bound monomer, not an amyloid fibril.
These flexible peptides can take other shapes. The trace shows one experimental conformation, with side chains and any binding partners omitted. Each view is scaled to fit.
PDB 2L86 · Solution NMRCalcitonin
Made mainly in C cells in the thyroid gland.
Its everyday job
It helps restrain bone breakdown, reducing calcium release from bone. Its role in everyday calcium balance in adults is smaller than that of parathyroid hormone and vitamin D.
Why therapies target it
It appears in obesity research because the calcitonin receptor is part of amylin receptors, and some experimental agents activate both receptor types.
That receptor overlap does not make natural calcitonin an incretin or establish it as a weight-control hormone.
Backbone trace · one bead per amino acid.
N and C mark the two ends of the chain.
About this structure
Native human calcitonin(1–32)-amide. Human calcitonin bound to human calcitonin receptor in an active Gs complex. Only the complete human calcitonin peptide is extracted. The native Cys1–Cys7 disulfide and terminal amidation are present. Receptor, G protein and nanobody are hidden; 2.7 Å is the reported global map resolution.
These flexible peptides can take other shapes. The trace shows one experimental conformation, with side chains and any binding partners omitted. Each view is scaled to fit.
PDB 7TYO · Cryo-electron microscopy