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The measurement of proinsulin in serum provides useful information for the diagnosis of insulinomas. Proinsulin levels have also been shown to be elevated in non-insulin-dependent diabetics (NIDDM), in insulin-dependent diabetics (IDDM), and in other clinical situations.

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Proinsulin is the precursor of insulin, which is the principal hormone responsible for the control of glucose metabolism. Proinsulin (PI), a polypeptide of 9390 MW (86 amino acids) is synthesized in the β cells of the Islets of Langerhans in the pancreas. This protein is processed into C-peptide and insulin forms. Both are secreted in equimolar amounts into the blood. Only 1% to 3% of proinsulin is secreted intact. However, because proinsulin has a longer half-life than insulin, circulating proinsulin concentrations are in the range of 5% to 30% of circulating insulin concentrations on a molar basis, with the higher relative proportions seen after meals and in patients with insulin resistance or early type 2 diabetes. Proinsulin can bind to the insulin receptor and exhibits 5% to 10% of the metabolic activity of insulin.

The level of proinsulin in serum can reflect beta cell status and a consequence of dysfunction of proinsulin processing and/or secretion. Proinsulin is increased in clinical conditions such as insulinoma, familial hyperinsulinemia, and non-insulin-dependent diabetes mellitus.

Proinsulin levels might be elevated in patients with insulin-producing islet cell tumors (insulinomas). These patients suffer from hypoglycemic attacks due to inappropriate secretion of insulin by the tumors. The inappropriate over-secretion of insulin by insulinomas causes the release of an increased number of secretory granules with incompletely processed insulin, resulting in elevated serum proinsulin concentrations

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