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Subject: Proinsulin

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  • Enzymatic process forms insulin in pancreatic secretory granules of beta cells. Proinsulin level is normally ≤20% of total insulin. Proinsulin has low biologic activity (10% insulin potency) and is the major storage form of insulin. Proinsulin is included in the immunoassay of total insulin, and separation requires special technique.

  • Normal range: 2.0–2.6 pmol/L.


  • Proinsulin: Insulin ratio is used as an indirect marker of beta cell function.


  • High proinsulin levels associated with benign or malignant beta cell tumors of the pancreas and endocrine pancreatic tumors associated with MEN-1.

  • Elevated levels are positive risk factor for the development of NIDDM.

  • Elevated levels in patients with chronic renal failure, cirrhosis, and hyperthyroidism.

  • Proinsulin >30% of serum insulin after overnight fast suggests insulinoma.

  • Proinsulin is increased in factitious hypoglycemia due to sulfonylurea.

  • Proinsulin is increased in familial hyperproinsulinemia—heterozygous mutation affecting cleavage of proinsulin leading to secretion of excess amounts of proinsulin.

  • Type 2 DM.


  • Proinsulin may also be increased in renal disease.

  • Elevation of proinsulin: insulin ratio correlates with a decreased acute illness response to glucose in patients with type 2 DM.