Growth hormone and prolactin stimulate the expression of rat preadipocyte factor-1/delta-like protein in pancreatic islets: molecular cloning and expression pattern during development and growth of the endocrine pancreas

C Carlsson, D Tornehave, Karen Lindberg, P Galante, N Billestrup, Birgitte Michelsen, L I Larsson, Jens Høiriis Nielsen

89 Citations (Scopus)

Abstract

GH and PRL have been shown to stimulate proliferation and insulin production in islets of Langerhans. To identify genes regulated by GH/PRL in islets, we performed differential screening of a complementary DNA library from neonatal rat islets cultured for 24 h with human GH (hGH). One hGH-induced clone had 96% identity with mouse preadipocyte factor-1 (Pref-1, or delta-like protein (Dlk)]. The size of Pref-1 messenger RNA (mRNA) in islets was 1.6 kilobases, with two less abundant mRNAs of 3.7 and 6.2 kilobases. The Pref-1 mRNA content of islets from adult rats was only 1% of that in neonatal islets. Pref-1 mRNA was markedly up-regulated in islets from pregnant rats from day 12 to term compared with those from age-matched female rats. Two peaks in mRNA expression were observed during gestation, one on day 14 and the other at term, whereafter it decreased to nonpregnant levels. Pref-1 mRNA was up-regulated 3- to 4-fold in neonatal rat islets of Langerhans after 48-h culture with hGH, as found also with bovine GH or ovine PRL. During the development of pancreas from embryonic day 12 (E12) to postnatal day 4, we observed a 2-fold increase in Pref-1 mRNA on E17 and a 5-fold increase at birth, followed by a rapid decline on postnatal day 4. Pref-1 immunoreactivity was found in a subpopulation of insulin cells of neonatal islets of Langerhans. At an early embryonal stage (E13), most cells of the pancreatic anlage were Pref-1 positive, becoming predominantly restricted to the insulin-producing cells during development. In conclusion, these findings suggest that Pref-1 is involved in both differentiation and growth of beta-cells.
Original languageEnglish
JournalEndocrinology
Volume138
Issue number9
Pages (from-to)3940-8
Number of pages9
ISSN0013-7227
Publication statusPublished - Sept 1997

Keywords

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Cloning, Molecular
  • Female
  • Gene Expression
  • Growth Hormone
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Islets of Langerhans
  • Male
  • Membrane Proteins
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Pregnancy
  • Prolactin
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Repressor Proteins
  • Sequence Alignment

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