Open AccessINSULIN BIOSYNTHESIS IN THE RAT: DEMONSTRATION OF TWO PROINSULINS
Author(s) -
Jeffrey L. Clark,
Donald F. Steiner
Publication year - 1969
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.62.1.278
Subject(s) - proinsulin , insulin , biosynthesis , islet , prohormone , medicine , in vitro , biology , biochemistry , endocrinology , peptide , chemistry , hormone , gene
Proinsulin, a single-chain precursor of insulin, has been detected in biosynthetic studiesin vitro ,1-4 and in crystalline preparations of insulin from several species.1, 5-7 It appears that proinsulin normally serves neither as a major storage nor secretory form of the hormone.8 Its primary functions seems to be to facilitate the efficient formation of the disulfide bonds of insulin.9 Although several species of fish have two insulins differing slightly in primary structure,10-12 the rat is the only mammal where this is known to be the case.13, 14 As the two rat insulins are nonallelic14 and presumably coded by two distinct genes, a separate proinsulin would be expected to precede each insulin. We have demonstrated the biosynthesis of both insulins15 and of a proinsulin corresponding to each in isolated islets of Langerhans, and have detected probable intermediates in the conversion of these proinsulins to insulin. Labeled peptide material corresponding to the free connecting segment of proinsulin (C-peptide) was detected in insulin-containing fractions isolated from incubated rat islets.It was noted that islets incubatedin vitro secreted small amounts ofnewly synthesized proinsulin as well as the two insulins and essentially equivalent amounts of C-peptide. Increasing the glucose content of the medium selectively enhanced the incorporation of radioactivity into proinsulin and insulin and also seemed to increase the relative proportion of labeled proinsulin appearing in the medium.