Proinsulin

Proinsulin is synthesized in the pancreatic beta cells as a 9390 mw polypeptide of 86 amino acids.^1-3 Proinsulin is subsequently cleaved enzymatically, releasing insulin into the circulation along with a residual 3000 mw fragment called C-peptide, so-named because it connects the A and B chains of insulin within the proinsulin molecule.

Proinsulin, which has relatively low biological activity (approximately 10% of insulin potency), is the major storage form of insulin. Normally, only small amounts (∼3% of the amount of insulin, on a molar basis) of proinsulin enter the circulation. Because the hepatic clearance of proinsulin is only 25% of insulin clearance, the half-life of proinsulin is two- to threefold longer and concentrations in the fasting state are approximately 10% to 15% of insulin concentrations.

High proinsulin concentrations have been associated with benign or malignant β-cell tumors of the pancreas⁴ and endocrine pancreatic tumors associated with MEN-1.⁵ Elevated proinsulin levels have been observed in individuals with impaired glucose tolerance even in the absence of abnormal glucose or C-peptide levels.⁶ Elevated proinsulin levels have been found to be a positive risk factor for the development on NIDDM.^7,8 Most patients with β-cell tumors have increased insulin, C-peptide, and proinsulin concentrations, but occasionally only proinsulin is elevated. Despite its low biological activity, proinsulin may be increased sufficiently to produce hypoglycemia.⁹ In addition, a rare form of familial hyperproinsulinemia, due to impaired conversion to insulin, has been described. Increased proinsulin concentrations may also be detected in patients with chronic renal failure, cirrhosis, or hyperthyroidism.

1. Clark PM. Assays for insulin, proinsulin(s) and C-peptide. Ann Clin Biochem. 1999; 36(Pt 5):541-564 (review). PubMed 10505204

2. Chevenne D, Ruiz J, Lohmann L, et al. Immunoradiometric assay of human intact proinsulin applied to patients with type 2 diabetes, impaired glucose tolerance, and hyperandrogenism. Clin Chem. 1994; 40(5):754-759. PubMed 8174247

3. Bowsher RR, Wolny JD, Frank BH. A rapid and sensitive radioimmunoassay for the measurement of proinsulin in human serum. Diabetes. 1992; 41(9):1084-1088. PubMed 1499862

4. Kao PC, Taylor RL, Service FJ. Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma. J Clin Endocrinol Metab. 1994; 78(5):1048-1051. PubMed 8175958

5. Oberg K, Skogseid B. The ultimate biochemical diagnosis of endocrine pancreatic tumours in MEN-1. J Intern Med. 1998; 243(6):471-476 (review). PubMed 9681845