Vasavada, “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

Transgenic overexpression of either parathyroid hor-mone-related peptide (PTHrP) or mouse placental lac-togen type 1 (mPL1) in pancreatic -cells, using the rat insulin II promoter (RIP), results in islet hyperplasia either through prolonged -cell survival or through increased -cell proliferation and hypertrophy, respec-tively. For determining whether the two proteins might exert complementary, additive, or synergistic effects on islet mass and function when simultaneously overex-pressed in -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, in-creased -cell proliferation (threefold), and resistance to the diabetogenic and cytotoxic effects of streptozotoci