Comparison

Exenatide vs MOTS-c

Function

While Exenatide is used for type 2 diabetes treatment to improve glycemic control and modestly reduce body weight through GLP-1–like insulinotropic and glucagonostatic effects6768, MOTS-c improves insulin sensitivity, enhances glycolysis, reduces oxidative stress, and shows protective effects in models of metabolic syndrome, aging, and ischemia-reperfusion injury8135146.

Mechanism

While Exenatide works as a 39-amino-acid exendin-4 peptide originally isolated from Gila monster venom that acts as a long-acting GLP-1 receptor agonist resistant to DPP-4 degradation67, MOTS-c is a 16-amino-acid mitochondrial-derived peptide that translocates to the nucleus under metabolic stress and regulates glucose and lipid metabolism largely via activation of AMPK and modulation of mTOR and folate-cycle–linked pathways854140146.

Length and Sequence

Exenatide is 39 amino acids long, whereas MOTS-c is shorter as it has a length of 16 amino acids. Exenatide is made up of a sequence of sequence data not available in the current dataset. MOTS-c is made up of a sequence of Methionine, Arginine, Tryptophan, Glutamine, Glutamic acid, Methionine, Glycine, Tyrosine, Isoleucine, Phenylalanine, Tyrosine, Proline, Arginine, Lysine, Leucine, Arginine.

Receptor

Exenatide

GLP-1 receptor (GLP1R) 6780

MOTS-c

No dedicated cell-surface receptor has been definitively identified; signaling is primarily described via intracellular AMPK and related metabolic pathways8135146

Organism or Origin

Exenatide

Originally from Heloderma suspectum (Gila monster) venom; now produced synthetically67

MOTS-c

Human mitochondrial peptide encoded in the 12S rRNA gene region54146

Gene

Exenatide

Not assigned in the current dataset.

MOTS-c

MT-RNR1

Sources

67Exendin 4 – Potent GLP-1R agonist - SB PEPTIDE, https://www.sb-peptide.com/project/exendin-4-potent-glp-1r-agonist/
68Glucagon-like peptide-1 analogues: An overview - PMC, https://pmc.ncbi.nlm.nih.gov/articles/PMC3712370/
80GLP-1 Localisation and Proglucagon Gene Expression in ..., https://pmc.ncbi.nlm.nih.gov/articles/PMC6200298/
8Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet ..., https://www.nature.com/articles/s12276-025-01521-1
54MOTS-c - Wikipedia, https://en.wikipedia.org/wiki/MOTS-c
135MOTS-c Promotes Glycolysis via AMPK-HIF-1α-PFKFB3 ... - PubMed, https://pubmed.ncbi.nlm.nih.gov/40035775/
146MOTS-c: A promising mitochondrial-derived peptide for therapeutic ..., https://pmc.ncbi.nlm.nih.gov/articles/PMC9905433/