Significance of Human Plasma Insulin Sephadex Fractions

15 min after oral glucose, the concentration of the proinsulin-like component was unchanged and its percentage of the total immunoreactive insulin decreased with the acute release of the insulin component. By 2 hr after oral glucose, the concentration of the proinsulin-like component increased and the insulin component concentration decreased so that the percentage of the proinsulin-like component was essentially the same as in the basal state.In five patients with islet cell tumors and fasting hypoglycemia, basal proinsulin-like component ranged from 26 to 79% of the total immunoreactive insulin. While basal proinsulin-like component was higher in the islet cell tumor patients, the fluctuations after stimulation were qualitatively similar to the nontumor patients. Acute stimulation with glucose, tolbutamide, leucine, and streptozotocin mainly released the insulin component resulting in a fall in the per cent proinsulin-like component with a subsequent increase in percentage of this component as the total insulin concentration returns towards basal levels. Three islet-cell tumor patients with less than 46% proinsulin-like component had favorable therapeutic responses to diazoxide whereas one patient with over 80% proinsulin-like component was completely refractory.Syrian hamsters bearing islet cell tumors provided an excellent model for islet cell tumors in man. These animals have a high proportion of a proinsulin-like component in plasma; stimulation of tumor slices in vitro with tolbutamide and glucagon releases mainly the insulin component similar to the observations in man.A portion of this work has appeared in abstract form (1).

Section: Resultssupporting

confidence: 78%

“…ponent is higher in islet-cell tumor patients than in most other patients studied, comprising from 26 to 79% of the total insulin. In individual cases a range of from 3 to 67% of basal and stimulated proinsulin-like component has been reported (1,15,16,(23)(24)(25).…”

Section: Resultsmentioning

confidence: 99%

Proinsulin-like component of circulating insulin in the basal state and in patients and hamsters with islet cell tumors

Görden¹,

Sherman²,

Roth³

1971

“…The proinsulin content of extracted pancreas is less than 7% of the immunoreactive insulin level (26)(27)(28)(29)(30)(31)(32), while basal values in peripheral blood are higher, comprising approximately 20% of total IRI (7,(33)(34)(35)(36). Although it has been suggested that the higher circulating proinsulin content indicates preferential release of newly formed granules, which contain a higher proportion of proinsulin, our data on portal vein blood indicate that the ratio of proinsulin to insulin being secreted is similar to that present in the pancreas.…”

Section: Discussionmentioning

confidence: 41%

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

Horwitz¹,

Starr²,

Mako³

et al. 1975

476

229

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.

“…Proinsulin, the single-chain polypeptide precursor of insulin, has been identified in human (1)(2)(3)(4)(5)(6), bovine (7,8), transaminase was assayed (18) in the initial and final perfusate sample from each experiment. The values were below 10 IU and did not increase significantly in the latter samples.…”

Section: Introductionmentioning

confidence: 99%

The Metabolism of Proinsulin and Insulin by the Liver

Rubenstein¹,

Pottenger²,

Mako³

et al. 1972

159

A B S T R A C T The removal of bovine proinsulin by the isolated perfused rat liver has been studied and the results compared with the removal of insulin. At high concentrations of insulin (> 180 ng/ml) the removal process was saturated and the ti varied between 35 and 56 min. With low initial insulin levels the disappearance followed first-order kinetics, the mean regression coefficient being -0.022, to 13.8 min, and the hepatic extraction 4.0 ml/min. The results with proinsulin were in striking contrast to these findings. At both high and low concentrations the hepatic removal of proinsulin was considerably slower, averaging 10-15 times less than that of insulin. Specific immunoassay techniques and gel filtration of samples taken from perfusions to which both labeled and unlabeled proinsulin had been added did not show conversion to either insulin or the C-peptide.Bovine and rat 'I-labeled proinsulins were degraded more slowly than bovine insulin-'1I by bovine and rat liver homogenates. Both proinsulin and insulin inhibited the degradation of insulin-tI, equimolar quantities of proinsulin being 2-5 times less effective than insulin.These results indicate significant differences in the capacity of the liver to remove and degrade insulin and proinsulin. The low hepatic extraction of proinsulin may account for its prolonged half-life in vivo and contribute to its relatively high plasma concentration in the fasting state. Furthermore this finding will have to be taken into account in the interpretation of changes in the proinsulin: insulin ratios in peripheral blood in a variety of metabolic situations.