Intended use
This immunoassay kit allows for the specific measurement of human Proinsulin concentrations in cell culture supernates, serum, and plasma.
Introduction
Proinsulin is synthesized in the pancreatic beta cells as a 9390 mw polypeptide of 86 amino acids. 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. Elevated proinsulin levels have been observed in individuals with impaired glucose tolerance even in the absence of abnormal glucose or C-peptide levels. Elevated proinsulin levels have been found to be a positive risk factor for the development on NIDDM. 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. 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.
