Proinsulin is the precursor of insulin and C-peptide. Following synthesis, proinsulin is packaged into secretory granules, where it is processed to C-peptide and insulin by prohormone convertases and carboxypeptidase E.
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.
Understand and improve your laboratory results with our health dashboard.
Upload your lab reports and get interpretation today.
Our technology helps to understand, combine, track, organize, and act on your medical lab test results.
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 biochemical diagnosis rests primarily on demonstrating nonsuppressed insulin levels in the presence of hypoglycemia (blood glucose <45 mg/dL). The diagnosis can be difficult, as tumors might be small or secrete insulin only episodically. Insulin injections or hypoglycemic drugs can also mimic insulinoma. Evaluation of these patients frequently requires a prolonged fast (72 hours) as well as supplementary tests in addition to insulin and glucose measurements, including a sulfonylurea screen and measurement of C-peptide, proinsulin, and beta-hydroxybutyrate. The inappropriate oversecretion of insulin by insulinomas causes the release of an increased numbers of secretory granules with incompletely processed insulin, resulting in elevated serum/plasma proinsulin concentrations. This oversecretion of proinsulin in insulinomas is accentuated during fasting, when proinsulin normally does not account for more than 5% of the insulin concentrations.
Proinsulin is strikingly elevated in PC1/3 deficiency. These patients have defects in the processing of multiple peptide hormones and suffer from diabetes, adrenal insufficiency, infertility, and obesity. Affected individuals typically have red hair regardless of racial background. Variants in the proinsulin molecule have been reported that affect PC cleavage efficiency or subsequent proinsulin metabolism. These variants can also lead to markedly elevated proinsulin levels but are usually not accompanied by diabetes or any other hormonal abnormalities.
Normal individuals will have proinsulin concentrations below the upper limit of the normal fasting reference range (22 pmol/L) when hypoglycemic (blood glucose <60 mg/dL). Conversely, most (>80%) insulinoma patients will have proinsulin concentrations above the upper limit of the reference range. The sensitivity and specificity for a diagnosis of insulinoma during hypoglycemia are approximately 75% and near 100%, respectively, at the 22 pmol/L cutoff.
Patients with PC1/3 deficiency have low, or sometimes undetectable, insulin levels and substantially elevated proinsulin levels, exceeding the upper limit of the reference range substantially in the fasting state and rising even higher after food intake. Many other hormonal abnormalities are also present, including cortisol deficiency (because of lack of processing of pro-opiomelanocortin to adrenocorticotropic hormone and other peptides), infertility, and, often, obesity.
Interpret Your Lab Results
Upload your lab report and we’ll interpret and provide you with recomendations today.Get Started
Get Started With Our Personal Plan
Are You a Health Professional?
Get started with our professional plan
Welcome to Healthmatters Pro.
Save time on interpreting lab results with the largest database of biomarkers online. In-depth research on any test at your fingertips, all stored and tracked in one place. Learn more
for health professionals
$45 per month
5-Methyltetrahydrofolate, Adiponectin, Albumin/Creatinine Ratio, Random Urine, Anti-Thyroglobulin ab. (0-39), C-Peptide, Serum, Ceruloplasmin, Creatinine, Random Urine, Cyclic AMP, Plasma, Dihydrotestosterone (female), Dihydrotestosterone (male), Estimated Average Glucose (eAG), Free Androgen Index, Free testosterone, Free Testosterone, Direct (Female), Free Testosterone, Direct (Male), Free Thyroxine, Free Thyroxine Index, Fructosamine, Glucose, Glutamic Acid Decarboxylase, Glycated Serum Protein (GSP), Hemoglobin A1c (HbA1c), HOMA-B, HOMA-IR, HOMA-S, Homocysteine, Insulin (Fasting), Insulin Antibody, Insulin-Like Growth Factor I (IGF-1), Iodine, Serum/Plasma, Parathyroid Hormone (PTH), Serum, Pregnenolone, Proinsulin, Reverse T3, Serum, Sex Hormone-Binding Globulin (SHBG), T3, Free, T4, Free, T4, Total (Thyroxine), T7 Index, Testosterone, Testosterone (Female/Child), Testosterone, Serum (Female), Thyroglobulin, Thyroglobulin Antibodies (0 - 1 IU/L), Thyroid Peroxidase Antibodies (Anti-TPO Ab), Thyroid Stim Immunoglobulin, Thyroid-Stimulating Hormone (TSH), Thyrotropin Receptor Ab, Serum, Thyroxine-binding globulin, TBG, TMAO (Trimethylamine N-oxide), Total T3, Tri iodothyronine (T3) Uptake, Triiodothyronine, Serum