MOTS-c

MOTS-c is a 16-amino-acid peptide. The 12S rRNA gene of the mitochondrial genome encodes it. It belongs to the mitochondrial-derived peptide (MDP) class.

MOTS-c activates AMPK. It disrupts the folate-methionine cycle and increases AICAR. This chain improves glucose uptake and insulin sensitivity.

It also regulates nuclear gene expression under metabolic stress. Named targets are GLUT4, STAT3, and IL-10.

Evidence tier: preclinical, plus human observational data.

Animal data. MOTS-c reverses diet-induced insulin resistance in mice. It improves glucose uptake in skeletal muscle. It restores metabolic flexibility in aged rodents.

Human data. The human evidence is observational, not interventional. Circulating MOTS-c decreases with age. The level is lower in people with type 2 diabetes.

One early clinical study carries a registration: NCT03998514, in obesity and fatty liver.

Evidence limit. No completed controlled human trial supports a MOTS-c treatment claim.

No high-authority human dosing exists.

MOTS-c does not cross the blood-brain barrier. Human pharmacokinetics are not fully characterized.

A theoretical additive risk of low blood glucose exists with metformin, insulin, or a sulfonylurea. All of them share an AMPK or insulin-sensitizing mechanism.

Compare with Humanin, the other mitochondrial-derived peptide in this library.

No clinical human safety data exist.

• Glucose.
• HbA1c.

No regulator approves MOTS-c. It is experimental.

At the July 2026 PCAC meeting, the FDA proposed not to add MOTS-c to the 503A bulks list. Read the PCAC July 2026 outcome.

WADA prohibits a non-approved substance under S0.