C-Peptide Physiology in Diabetic Vascular Complications

C-peptide, a cleavage product of proinsulin, has emerged as an active modulator of vascular function rather than an inert by-product. In diabetes, loss of endogenous C-peptide correlates with endothelial dysfunction, impaired microvascular blood flow and heightened oxidative stress. Physiologically, C-peptide binds to cell surface receptors on endothelial cells, activating intracellular calcium signalling and endothelial nitric oxide synthase, thereby restoring nitric oxide bioavailability and normalising vasomotor tone. Beyond hemodynamic effects, C-peptide attenuates hyperglycaemia-induced reactive oxygen species and inhibits transglutaminase activity, mitigating the persistent endothelial permeability that underlies retinopathy, nephropathy and atherosclerosis. Restoration of physiologic C-peptide levels has been shown to improve capillary red blood cell deformability, reduce leukocyte adhesion and rebalance pro- and anti-angiogenic factors. Collectively, these actions position C-peptide as a multi-faceted regulator of diabetic vascular health, with potential to prevent or reverse microvascular and macrovascular complications through both systemic and local delivery strategies.

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C-Peptide Physiology in Diabetic Vascular Complications publication trend

The graph below shows the total number of articles in c-peptide physiology in diabetic vascular complications across all publications each year (not limited to Nature Index journals).

Technical terms

C-peptide: A 31-amino-acid peptide released during insulin biosynthesis that exerts direct vascular effects.

Endothelial dysfunction: Impaired function of the vascular lining leading to reduced nitric oxide production and increased permeability.

Neovascularisation: Formation of new blood vessels, often pathological in diabetic retinopathy.

Hyperglycaemic memory: Persistence of vascular damage mechanisms despite subsequent blood glucose normalisation.

Reactive oxygen species: Chemically reactive molecules derived from oxygen that can damage cellular structures and impair vascular function.

References

1. Therapeutic effect of ultra-long-lasting human C-peptide delivery against hyperglycemia-induced neovascularization in diabetic retinopathy. Theranostics (2023).
2. Simultaneous attenuation of hyperglycemic memory-induced retinal, pulmonary, and glomerular dysfunctions by proinsulin C-peptide in diabetes. BMC Medicine (2023).
3. The association of serum C-peptide with the risk of cardiovascular events: a meta-analysis and systematic review. Diabetology & Metabolic Syndrome (2023).