Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood.

Abstract

A B S T R A C T Concentrations of insulin, proinsulin, and C-peptide were measured in portal and peripheral venous blood in six nondiabetic, nonobese subjects. Portal vein samples were obtained by umbilical vein catheterization. Three subj ects were studied with intravenous infusion of 25 g glucose, and three with 30 g arginine. Insulin and proinsulin were determined in the insulin immunoassay after separation by gel filtration, and C-peptide was measured by direct immunoassay.With both glucose and arginine stimulation, portal vein levels of all three peptides peaked at 90-120 s after the onset of the stimulus. Relative increases in insulin concentration were greater than those of proinsulin or C-peptide. In peripheral venous blood, maximal levels of the three peptides were observed later (2-5 min), and the increase in insulin relative to proinsulin and C-peptide was not as great. At the time of peak secretion, portal vein insulin and C-peptide approached equimolar concentrations, and proinsulin, as measured against an insulin standard, comprised approximately 2.5% of the total immunoreactive insulin.After stimulation by glucose or arginine, portal insulin, proinsulin, and C-peptide levels were not correlated with the concentrations measured in simultaneously drawn peripheral samples. At all sampling times, however, significant correlation was found between insulin and C-peptide in both peripheral and portal blood. The results indicate that under the conditions studied, insulin and C-peptide are secreted in equimolar concentrations in man, and that proinsulin is secreted in the same proportion to insulin as found in the pancreas.

Loss of beta cell function as fasting glucose increases in the non-diabetic range

“…Measures of pre-hepatic pancreatic insulin secretion were derived using C-peptide concentrations. C-peptide is secreted from the pancreas simultaneously and in equimolar quantities with insulin but is not taken up by the liver and, once in the peripheral circulation, has simpler distributional characteristics [29]. This has allowed effective working simplifications of C-peptide behaviour, which enable model-based estimates of the true pancreatic insulin secretion rate to be derived.…”

The in vivo regulation of pulsatile insulin secretion

“…Insulin and C-peptide are co-released in a 1 to 1 molar ratio [77]. Whereas insulin undergoes substantial (40±80 %) and variable [66, 78±80] hepatic-insulin extraction [81], C-peptide is presumably not cleared by the liver [82], which resulted in a predominance of the use of C-peptide when calculating the overall insulin secretory rates.…”

Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels

“…Thus, patients with diabetes under insulin therapy show the highest insulin resistance and the highest insulin levels in the peripheral blood. Peripheral insulin concentrations do reflect those in the portal vein (8), even in patients under insulin therapy. In patients without diabetes, increasing peripheral insulin levels by exogenous insulin suppresses the hepatic glucose production but in diabetics under insulin therapy the hepatic glucose production cannot be inhibited by plasma insulin concentrations throughout the physiologic range.…”