title: Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Danish Diabetes Academy, Odense University Hospital, Odense, Denmark; Centre for Fetal Programming, Copenhagen, Denmark.
authors.forename: Amarnadh
authors.initials: A
authors.lastname: Nalla
authors.forename: Lene
authors.initials: L
authors.lastname: Ringholm
authors.forename: Brigitte
authors.initials: B
authors.lastname: Søstrup
authors.forename: Peter
authors.initials: P
authors.lastname: Højrup
authors.forename: Lars
authors.initials: L
authors.lastname: Thim
authors.forename: Steven B
authors.initials: SB
authors.lastname: Levery
authors.forename: Sergey Y
authors.initials: SY
authors.lastname: Vakhrushev
authors.forename: Nils
authors.initials: N
authors.lastname: Billestrup
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Mathiesen
authors.forename: Peter
authors.initials: P
authors.lastname: Damm
authors.forename: Jens H
authors.initials: JH
authors.lastname: Nielsen
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000595:Amino Acid Sequence; D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D016632:Apolipoprotein A-I / Q000097:blood; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007704:Kininogens / Q000097:blood; D013058:Mass Spectrometry; D010928:Placental Lactogen / Q000097:blood; D011247:Pregnancy; D011264:Pregnancy Trimesters; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D015415:Biomarkers; C000591034:KNG1 protein, human; D007704:Kininogens; D012709:Serum Albumin; D000515:alpha 1-Antitrypsin; C464794:fibrinogen Aalpha; D000808:Angiotensinogen; D005340:Fibrinogen; D010928:Placental Lactogen
keywords: INS-1E cell line; Pregnancy; beta cells; growth factors; islets; proliferation; survival