C-Peptide

Metabolic / Vascular

Also known as: Connecting Peptide, Insulin C-Peptide

Insulin-Related PeptidesResearch phase: Phase 2Regulatory: Not approved as drug. Used clinically as biomarker for endogenous insulin production. Therapeutic trials ongoing.

Mechanism

C-peptide is the connecting fragment cut out when proinsulin becomes insulin. Once thought to be inert, it is now known to have its own biological activity, improving nerve and kidney function in diabetic complications.

Technical detail

C-peptide is a 31-amino acid peptide released from pancreatic beta cells in equimolar amounts with insulin during proinsulin processing. It activates a G-protein coupled receptor (likely GPR146) stimulating Na+/K+-ATPase and eNOS activity, improving microvascular blood flow, nerve conduction, and renal function. Phase 2 trials of C-peptide replacement in type 1 diabetes showed improvements in peripheral neuropathy and nephropathy.

Evidence

  • Amelioration of sensory nerve dysfunction by C-Peptide in patients with type 1 diabetes.

    Ekberg et al. (2003) — Diabetes — PMID: 12540632

    Randomized double-blind placebo-controlled study in type 1 diabetes patients with early neuropathic findings showed 3 months of replacement-dose C-peptide improved sural sensory nerve conduction velocity and vibration perception versus placebo, suggesting biologic benefit in early diabetic neuropathy.

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