Metabolism and placental transfer of /sup 125/I-proinsulin and /sup 125/I-tyrosylated C-peptide in the pregnant rhesus monkey

Journal Article · Thu Oct 01 04:00:00 EDT 1987 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI113170· OSTI ID:5841735

Gruppuso, P A; Susa, J B; Sehgal, P; Frank, B; Schwartz, R

/sup 125/I-Proinsulin or /sup 125/I-tyrosylated-C-peptide (/sup 125/I-tyr-CP) was administered to pregnant Rhesus monkeys by bolus followed by constant infusion to examine placental transfer of these peptides. At the end of each infusion, fetuses were exsanguinated in situ via the umbilical vein. The bolus-constant infusion technique produced a steady state in maternal plasma of immunoprecipitable label, measured using excess insulin or C-peptide antiserum. In animals infused with /sup 125/I-proinsulin, analysis of umbilical venous plasma revealed no apparent transfer to the fetus of immunoprecipitable label. In animals infused with /sup 125/I-tyr-CP, 3-13% of the umbilical venous plasma radioactivity was immunoprecipitable, representing 1.4-5.8% of the immunoprecipitable radioactivity in maternal plasma at delivery. Gel filtration chromatography of umbilical venous plasma revealed that the immunoprecipitated moiety was a fragment of /sup 125/I-tyr-CP. Analysis of maternal plasma showed that the predominant peak of radioactivity represented intact C-peptide. A peak corresponding to the fetal immunoprecipitable peak was also present. Analysis of simultaneous maternal arterial and uterine vein plasma samples showed that degradation of /sup 125/I-tyr-CP occurred across the uterus. Studies in one nonpregnant and three postpartum animals indicated that pregnancy increased the rate of metabolism of /sup 125/I-tyr-CP. When /sup 125/I-tyr-CP was incubated with trophoblastic cells in culture, degradation to a species corresponding on gel filtration to the immunoprecipitable fetal metabolite was found. We conclude that proinsulin, like insulin, does not traverse the placenta. Immunoreactive fragments of C-peptide do cross, however, and pregnancy alters the metabolism of /sup 125/I-tyr-CP, probably owing to placental degradation.

• Research Organization: Rhode Island Hospital, Providence
• OSTI ID: 5841735
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 80:4; ISSN JCINA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
FETAL MEMBRANES
FETUSES
GLANDS
HORMONES
HYDROXY ACIDS
IMMUNE REACTIONS
IMMUNOASSAY
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIVER
MAMMALS
MEMBRANE TRANSPORT
MEMBRANES
METABOLISM
MONKEYS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
PLACENTA
PREGNANCY
PRIMATES
PROTEINS
RADIOISOTOPES
SEPARATION PROCESSES
TRACER TECHNIQUES
TYROSINE
VERTEBRATES