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The 31-residue linker cut out of proinsulin — long dismissed as inert, then studied as a therapy, and today mostly a laboratory measure of how much insulin a pancreas still makes.
Also known as: Proinsulin C-peptide · Connecting peptide · Insulin C-peptide
Part of the Metabolic & GLP-1 peptides cluster
Overview
C-peptide is the 31-amino-acid connecting peptide released when proinsulin is cleaved into insulin, produced in equimolar amounts with insulin and used clinically as a measure of β-cell function. Research since the 1990s found that it binds cell membranes and signals through G-protein and calcium-dependent pathways, prompting trials as a therapy for diabetic complications; no C-peptide product is approved.
Source & context
Biological / chemical source: Cleaved from proinsulin in pancreatic β-cells (human)
Primary research or clinical context: Endogenous peptide and clinical biomarker of β-cell function; investigated as a replacement therapy for type 1 diabetes complications, with no approved product
What C-peptide is
Insulin is made as a single chain, proinsulin, in which the B and A chains are joined by a 31-residue connecting segment. When proinsulin is processed, that segment is cut out and released alongside the mature hormone, so C-peptide “is produced in equimolar amounts to endogenous insulin but is excreted at a more constant rate over a longer time” (Leighton et al., Diabetes Therapy 2017). The IUPHAR Guide to Pharmacology records the human sequence as EAEDLQVGQVELGGGPGAGSLQPLALEGSLQ; PubChem lists it at about 3,020 Da. For decades it was regarded as a by-product with no function — “an assumption was made that C-peptide, a byproduct of insulin biosynthesis, possessed no appreciable physiologic role” (Grunberger and Sima, Experimental Diabesity Research 2004).
Why clinicians measure it
Because it is released one-for-one with insulin but cleared more slowly, C-peptide is “a widely used measure of pancreatic beta cell function” (Leighton et al., Diabetes Therapy 2017). It can be measured in urine or in unstimulated and stimulated serum samples, and modern assays detect levels low enough to help classify diabetes and guide treatment decisions (Leighton et al. 2017). A person taking injected insulin still has measurable C-peptide only if their own β-cells are working, which is what makes the test informative. This diagnostic role is uncontested and is the reason “C-peptide test” is the most common form of the search.
The case that it is a hormone
From the 1990s onward, experimental work argued that C-peptide is biologically active. It “binds specifically to cell membranes, elicits intracellular signaling via G-protein and Ca2+-dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+,K+-ATPase and several transcription factors of importance for anti-inflammatory, anti-oxidant and cell protective mechanisms” (Wahren and Larsson, Diabetes Research and Clinical Practice 2015). Mounting evidence was said to support a biological role in diabetic kidney disease, where C-peptide “may beneficially affect the disturbed metabolic and pathophysiological pathways” (Brunskill, Journal of Internal Medicine 2017). Whether it acts through a dedicated receptor or an interaction with a related membrane entity was left open (Grunberger and Sima 2004).
Therapeutic trials and the “trough of disillusionment”
The hormone hypothesis led to studies in animal models of diabetes and early clinical trials of C-peptide replacement in type 1 diabetes (Wahren and Larsson 2015; Washburn et al., Biomedicines 2021). Replacement “has been shown to reduce diabetes-related complications” in that literature, yet a 2017 commentary asked whether the field was “in the trough of disillusionment” (Pinger et al., Molecular BioSystems 2017), and a 2021 review concluded that “the peptide has turned out not to be important in the treatment of diabetes,” while noting that every phase of its study changed how peptide-hormone processing and biology are understood (Landreh and Jörnvall, Cellular and Molecular Life Sciences 2021). No C-peptide therapeutic has reached approval.
Relation to insulin and other site peptides
C-peptide's parent, insulin, has its own profile, as do the incretin hormones (GLP-1, GIP) that regulate its secretion. The connecting peptide has no structural relationship to any of them beyond its origin in proinsulin, and it is not an insulin substitute: measuring it tells you about insulin production, giving it does not lower glucose. Readers who encounter “C-peptide” in a laboratory report are looking at a biomarker; readers who encounter it in a research catalogue are looking at an investigational compound with a contested mechanism.
| Property | Value |
|---|---|
| Length | 31 residues |
| Origin | Proinsulin residues 57–87, cleaved during insulin maturation |
| Secretion | Equimolar with insulin, cleared more slowly |
| Clinical use | Biomarker of β-cell function (serum or urine) |
| Therapeutic status | Investigational; no approved product |
Regulatory status
C-peptide is an endogenous peptide and a laboratory analyte; assays for it are standard diagnostics. As a therapy it is investigational, with early clinical trials conducted and a company-sponsored programme reflected in the 2015 review's affiliations (Wahren and Larsson 2015), but no marketing authorisation anywhere as of September 2026. ClinicalTrials.gov returns more than 2,000 studies for the term because C-peptide is measured as an outcome in trials across diabetes and oncology; almost none of those test it as a treatment.
Sequence
One-letter sequence commonly cited for C-peptide (educational; isoforms and modifications may differ):
EAEDLQVGQVELGGGPGAGSLQPLALEGSLQ
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- 31-residue linear peptide connecting the B and A chains of proinsulin (UniProt P01308, residues 57–87)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Free acid
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C129H211N35O48
- Average reference mass
- ≈ 3,020.3
- Receptors
- Binds specifically to cell membranes; a specific cell-surface receptor has been proposed but the signalling partner is not definitively identified
- Backbone
- 31-residue linear peptide connecting the B and A chains of proinsulin (UniProt P01308, residues 57–87)
- C-terminus
- Free acid
- Status
- Endogenous peptide and diagnostic biomarker; investigational as a therapy, no approved product as of September 2026
- PubChem CID: 16157840
- IUPHAR ligand: 6145
- CAS RN: 33017-11-7
- UNII: O2J76Y002M
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 2,353 registered studies with “C-peptide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT01854827 | Safety Study of Intravenous Immunoglobulin (IVIG) Post-Portoenterostomy in Infants With Biliary Atresia | Phase 2 | completed | 2026-10-01 |
| NCT06589804 | Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returni | Phase 3 | recruiting | 2026-10-01 |
| NCT05063552 | Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy | Phase 3 | active not recruiting | 2026-10-01 |
| NCT02224781 | Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafe | Phase 3 | active not recruiting | 2026-10-01 |
| NCT04628767 | Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Uppe | Phase 3 | recruiting | 2026-10-01 |
| NCT01274338 | Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has | Phase 3 | active not recruiting | 2026-10-01 |
C-peptide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: 31-residue linear peptide connecting the B and A chains of proinsulin (UniProt P01308, residues 57–87)Average reference mass: 3,020.3 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- TrialsHighest registered trial phase moved from phase 4 to phase 3.
- Trials13 registered studies added on ClinicalTrials.gov (now 2353).
- IdentifiersCross-linked to IUPHAR ligand 6145 and PubChem CID 16157840.
- TrialsClinicalTrials.gov snapshot added: 2340 registered studies, highest phase 4.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about C-peptide
What is C-peptide?+
C-peptide is the 31-amino-acid connecting peptide released when proinsulin is cleaved into insulin, produced in equimolar amounts with insulin and used clinically as a measure of β-cell function. Research since the 1990s found that it binds cell membranes and signals through G-protein and calcium-dependent pathways, prompting trials as a therapy for diabetic complications; no C-peptide product is approved.
What Canadian product status is recorded for C-peptide?+
Canadian product status for C-peptide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of C-peptide?+
C-peptide is commonly described as approximately 31 amino acids (Proinsulin connecting peptide).
What is C-peptide?+
The 31-amino-acid connecting peptide cut out of proinsulin when insulin is made. It is released in equal amounts to insulin and is measured to assess how much insulin the pancreas still produces.
What does a C-peptide test show?+
β-cell function. Because C-peptide is co-released with insulin but cleared more slowly, its level reflects endogenous insulin production even in people injecting insulin.
Is C-peptide a hormone?+
Experimental work shows it binds membranes and triggers G-protein and calcium signalling, and it was tested as a therapy for diabetic complications. A 2021 review concluded it turned out not to be important for treating diabetes; the question is still debated.
What is the sequence of C-peptide?+
EAEDLQVGQVELGGGPGAGSLQPLALEGSLQ — 31 residues, corresponding to proinsulin residues 57–87.
Is C-peptide approved as a treatment?+
No. It is investigational; no C-peptide therapeutic is approved anywhere as of September 2026.
Related peptides
References & further reading
- 1.Wahren & Larsson (2015). C-peptide: new findings and therapeutic possibilities. Diabetes Research and Clinical Practice
- 2.Landreh & Jörnvall (2021). Biological activity versus physiological function of proinsulin C-peptide. Cellular and Molecular Life Sciences
- 3.Leighton et al. (2017). A Practical Review of C-Peptide Testing in Diabetes. Diabetes Therapy
- 4.Brunskill (2017). C-peptide and diabetic kidney disease. Journal of Internal Medicine
- 5.Washburn et al. (2021). C-Peptide as a Therapy for Type 1 Diabetes Mellitus. Biomedicines
- 6.Pinger et al. (2017). C-Peptide replacement therapy in type 1 diabetes: are we in the trough of disillusionment? Molecular BioSystems
- 7.Grunberger & Sima (2004). The C-peptide signaling. Experimental Diabesity Research
- 8.PubChem — C-Peptide (CID 16157840)