2021 May 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.
C-peptide (connecting peptide) connects alpha and beta chains of proinsulin, which are formed in the endoplasmic reticulum following the removal of the signal peptide of pre-proinsulin. It is secreted from the beta cells of islets of Langerhans of the endocrine pancreas when proinsulin is cleaved into insulin and C-peptide. It plays an important role in the correct folding of insulin and the formation of disulfide bridges. C-peptide is removed in the Golgi apparatus from proinsulin resulting in the formation of the mature insulin molecule with both alpha and beta chains bound together by disulfide bonds. Both insulin and C-peptide are stored in secretory vesicles and released in equimolar concentrations upon stimulation of beta cells by glucose and other secretagogues. The most important indications for measurement of C-peptide levels include the differential diagnosis of fasting hypoglycemia with hyperinsulinism and as a measure of insulin secretory reserve. This brief review covers the relevant biochemistry, measurement, and clinical indications.