Characterization of Mice Doubly Transgenic for Parathyroid Hormone-Related Protein and Murine Placental Lactogen

A Novel Role for Placental Lactogen in Pancreatic β-Cell Survival

  1. Yuichi Fujinaka,
  2. Darinka Sipula,
  3. Adolfo Garcia-Ocaña and
  4. Rupangi C. Vasavada
  1. From the Division of Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  1. Address correspondence and reprint requests to Rupangi C. Vasavada, Ph.D., Division of Endocrinology, BST E-1140, University of Pittsburgh School of Medicine, 3550 Terrace St., Pittsburgh, PA 15213. E-mail: vasavada{at}


Transgenic overexpression of either parathyroid hormone-related peptide (PTHrP) or mouse placental lactogen type 1 (mPL1) in pancreatic β-cells, using the rat insulin II promoter (RIP), results in islet hyperplasia either through prolonged β-cell survival or through increased β-cell proliferation and hypertrophy, respectively. For determining whether the two proteins might exert complementary, additive, or synergistic effects on islet mass and function when simultaneously overexpressed in β-cells in vivo, RIP-PTHrP and RIP-mPL1 mice were crossed to generate mice doubly transgenic for PTHrP and mPL1. These double-transgenic mice displayed marked islet hyperplasia (threefold), hypoglycemia, increased β-cell proliferation (threefold), and resistance to the diabetogenic and cytotoxic effects of streptozotocin compared with their normal siblings. Although the phenotype of the double-transgenic mice was neither additive nor synergistic relative to their single-transgenic counterparts, it was indeed complementary, yielding the maximal salutary phenotypic features of both individual transgenes. Finally, mPL1, for the first time, was shown to exert a protective effect on the survival of β-cells, placing it among the few proteins that can improve function and proliferation and prolong the survival of β-cells. Placental lactogen 1 is an attractive target for future therapeutic strategies in diabetes.


    • Accepted August 19, 2004.
    • Received May 3, 2004.
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