Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy. / Nalla, Amarnadh; Ringholm, Lene; Søstrup, Birgitte; Højrup, Peter; Thim, Lars; Levery, Steven B; Vakhrushev, Sergey Y; Billestrup, Nils; Mathiesen, Elisabeth R; Damm, Peter; Nielsen, Jens H.
I: Acta Obstetricia et Gynecologica Scandinavica, Bind 93, Nr. 11, 11.2014, s. 1181-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy
AU - Nalla, Amarnadh
AU - Ringholm, Lene
AU - Søstrup, Birgitte
AU - Højrup, Peter
AU - Thim, Lars
AU - Levery, Steven B
AU - Vakhrushev, Sergey Y
AU - Billestrup, Nils
AU - Mathiesen, Elisabeth R
AU - Damm, Peter
AU - Nielsen, Jens H
N1 - © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.
PY - 2014/11
Y1 - 2014/11
N2 - OBJECTIVE: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors.SAMPLES: Serum samples from nonpregnant and pregnant women.METHODS: The effect of serum from pregnant women on the proliferation of rat beta cells was studied using [3H]thymidine incorporation and 5-ethynyl-2'-deoxyuridine proliferation assays. In addition, serum from pregnant and nonpregnant women was fractionated by gel filtration and high performance liquid chromatography. The fractionated serum was screened for mitogenic activity in INS-1E cells. Proteins and peptides in mitogenic active serum fractions were identified by amino acid sequencing and mass spectrometry.MAIN OUTCOME MEASURES: Presence of circulating beta cell proliferating factors.RESULTS: Late gestational pregnancy serum significantly increased proliferation of rat beta cells compared with early pregnancy and nonpregnancy. The mitogenic active serum fractions contained proteins and peptides derived from kininogen-1, fibrinogen-α, α1-antitrypsin, apolipoprotein-A1, placental lactogen, angiotensinogen and serum albumin.CONCLUSION: Pregnancy serum is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.
AB - OBJECTIVE: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors.SAMPLES: Serum samples from nonpregnant and pregnant women.METHODS: The effect of serum from pregnant women on the proliferation of rat beta cells was studied using [3H]thymidine incorporation and 5-ethynyl-2'-deoxyuridine proliferation assays. In addition, serum from pregnant and nonpregnant women was fractionated by gel filtration and high performance liquid chromatography. The fractionated serum was screened for mitogenic activity in INS-1E cells. Proteins and peptides in mitogenic active serum fractions were identified by amino acid sequencing and mass spectrometry.MAIN OUTCOME MEASURES: Presence of circulating beta cell proliferating factors.RESULTS: Late gestational pregnancy serum significantly increased proliferation of rat beta cells compared with early pregnancy and nonpregnancy. The mitogenic active serum fractions contained proteins and peptides derived from kininogen-1, fibrinogen-α, α1-antitrypsin, apolipoprotein-A1, placental lactogen, angiotensinogen and serum albumin.CONCLUSION: Pregnancy serum is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.
KW - Adaptation, Physiological
KW - Adult
KW - Amino Acid Sequence
KW - Angiotensinogen
KW - Animals
KW - Animals, Newborn
KW - Apolipoprotein A-I
KW - Biological Markers
KW - Cell Proliferation
KW - Cells, Cultured
KW - Chromatography, Gel
KW - Chromatography, High Pressure Liquid
KW - Female
KW - Fibrinogen
KW - Humans
KW - Insulin-Secreting Cells
KW - Kininogens
KW - Mass Spectrometry
KW - Placental Lactogen
KW - Pregnancy
KW - Pregnancy Trimesters
KW - Rats
KW - Rats, Wistar
KW - Serum Albumin
KW - alpha 1-Antitrypsin
U2 - 10.1111/aogs.12505
DO - 10.1111/aogs.12505
M3 - Journal article
C2 - 25223212
VL - 93
SP - 1181
EP - 1189
JO - Acta Obstetricia et Gynecologica Scandinavica
JF - Acta Obstetricia et Gynecologica Scandinavica
SN - 0001-6349
IS - 11
ER -
ID: 132899552