A Direct Assay for Proinsulin in Plasma and Its Applications in Hypoglycaemia

Abstract

A direct radioimmunoassay in unextracted plasma is described. The assay has a sensitivity of 4 pmol/l (2 standard deviation from zero). The proinsulin antiserum was immuno-adsorbed against human C-peptide and insulin coupled to glass beads. Cross-reactivity of the antiserum was assessed and shown to be less than 0.01% with both peptides. In normal healthy fasting subjects the plasma proinsulin level was 6.7 +/- 1.7 pmol/l (n = 17) (mean +/- SD). Fasting proinsulin levels in non-insulin dependent diabetics were significantly elevated compared with non diabetics (14.2 +/- 2 pmol/l (n = 11) vs 6.7 +/- 1.7 (n = 17) P less than 0.005). The insulin/proinsulin ratio was 3.4:1 in the non-insulin dependent diabetic compared with 6:1 in non-diabetics. Samples from 21 insulinoma patients were assayed and mean fasting plasma proinsulin level was 255 pmol/l +/- 479 when the patients were hypoglycaemic. The range in pro-insulin levels was large (30-2300 pmol/l). Mean fasting proinsulin level in three hypoglycaemic subjects due to sulphonylurea overdose was 15.7 +/- 2.3 pmol/l. The molar ratio of proinsulin to insulin was 1:6 in healthy subjects, 1:1 in insulinoma patients and 10:1 in sulphonylurea induced hypoglycaemic patients.

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

“…The 32-33 split proinsulin level was undetectable (!2 pmol/l). These findings, together with an appropriate ratio of proinsulin to insulin (19%) below the O25% ratio seen in insulinoma patients (5,6), are consistent with those observed in non-insulinoma insulin hypersecretion. The sulphonylurea screen was negative.…”

Hypoglycemic Syndrome in a Patient with Proinsulin-Only Secreting Pancreatic Adenoma (Proinsulinoma)

“…It has been previously pointed out that the use of highly specific plasma insulin immunoassays reduce the chances of identifying patients with high proinsulin concentrations and possible proinsulinomas [5, 6]. However, proinsulin-only secreting tumors are very rare (a few cases are described in the literature [6–9]) while pancreatic endocrine tumors usually produce and secrete both insulin and proinsulin [10, 11]. Anatomical diagnosis was finally confirmed with selective angiography, the most invasive and accurate approach, providing information of vascular density and origin.…”

Hiperinsulinismo endógeno: revisão e seguimento de 24 casos

“…Apesar disso, nossos pacientes submetidos ao teste do jejum prolongado ou do jejum de 12h apresentaram positividade para todos os critérios: glicose plasmática < 55 mg/dL, insulina > 3 uU/mL, peptídeo-C > 0,6 ng/mL e relação I/G > 0,3. Caso seja necessá-rio, o diagnóstico diferencial entre HHE e as outras hipoglicemias de jejum pode ser melhorado usando-se o "Amended I/G" (26).…”