A number of insulin-like and proinsulin-like polypeptides were employed in the study of the structure-activity relationship of proinsulin. Glucose incorporation into CO2 and lipids, and the antilipolytic activity, were used as parameters to measure the biological activity of these polypeptides. The split proinsulin and the long A chain proinsulin, with 2 connecting amino acid residues, Arg-Arg,...

BACKGROUND AND PURPOSE Insulin resistance and hyperinsulinemia have been associated with atherosclerosis. Recent attention has focused on the possible role of proinsulin because most radioimmunoassays for insulin cross-react with proinsulin. Therefore, it is not known which of the two, insulin per se or proinsulin, is more strongly related to atherosclerosis. METHODS We examined the relation ...

In heterozygous patients with a diabetic syndrome called mutant INS gene-induced diabetes of youth (MIDY), there is decreased insulin secretion when mutant proinsulin expression prevents wild-type (WT) proinsulin from exiting the endoplasmic reticulum (ER), which is essential for insulin production. Our previous results revealed that mutant Akita proinsulin is triaged by ER-associated degradati...

In patients with non-insulin-dependent diabetes mellitus, concentrations in plasma of insulin and its precursors, proinsulin and split proinsulin, are increased. Because increased concentrations of plasminogen activator inhibitor type-1 (PAI-1) occur also, we hypothesized that proinsulin and split proinsulin may augment endothelial cell PAI-1 expression, thereby potentially attenuating endogeno...

BACKGROUND Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM. METHODS We compared serum insu...

A specific antibody against proinsulin has been obtained by adsorbing the original anti-proinsulin guinea pig serum with a solid immunosorbent of Sephadex-insulin. The specificity of the antibody against antigenic determinants of proinsulin was established by radioimmunoassay and by passive cutaneous anaphylaxis (PCA) tests. The presence of proinsulin in calf serum has been demonstrated by (a) ...

The neuroendocrine processing endoproteases PC2 and PC1/3 are expressed in the beta cells of the islets of Langerhans and participate in the processing of proinsulin to insulin and C-peptide. We have previously shown that disruption of PC2 (SPC2) expression significantly impairs proinsulin processing. Here we report that disruption of the expression of PC1/3 (SPC3) produces a much more severe b...

A method has been described for the direct measurement of proinsulin in human plasma. The method makes use of an insulin-degrading enzyme designated "insulin-specific protease (ISP)", which is obtained from rat skeletal muscle. Under the conditions used, this enzyme rapidly degrades insulin and insulin-like polypeptides to nonimmunoassayable components, whereas proinsulin and proinsulin cleaved...

OBJECTIVE Excessive secretion of the insulin precursor proinsulin, as manifested by an increased serum proinsulin-to-insulin ratio, has been associated with beta-cell dysfunction. In women with gestational diabetes mellitus (GDM), previous studies of the proinsulin-to-insulin ratio have yielded conflicting results, despite the presence of beta-cell dysfunction. The interpretation of the proinsu...

Proinsulin gene expression regulation and function during early embryonic development differ remarkably from those found in postnatal organisms. The embryonic proinsulin protein content decreased from gastrulation to neurulation in contrast with the overall proinsulin messenger RNA increase. This is due to increasing levels of a proinsulin mRNA variant generated by intron 1 retention in the 5' ...