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J Biol Chem, Vol. 275, Issue 20, 15399-15406, May 19, 2000
From the The factors that regulate pancreatic beta cell
proliferation are not well defined. In order to explore the role of
murine placental lactogen (PL)-I (mPL-I) in islet mass regulation
in vivo, we developed transgenic mice in which mPL-I is
targeted to the beta cell using the rat insulin II promoter. Rat
insulin II-mPL-I mice displayed both fasting and postprandial
hypoglycemia (71 and 105 mg/dl, respectively) as compared with normal
mice (92 and 129 mg/dl; p < 0.00005 for both). Plasma
insulin concentrations were inappropriately elevated, and insulin
content in the pancreas was increased 2-fold. Glucose-stimulated
insulin secretion by perifused islets was indistinguishable from
controls at 7.5, 15, and 20 mM glucose. Beta cell
proliferation rates were twice normal (p = 0.0005).
This hyperplasia, together with a 20% increase in beta cell size,
resulted in a 2-fold increase in islet mass (p = 0.0005) and a 1.45-fold increase in islet number (p = 0.0012). In mice, murine PL-I is a potent islet mitogen, is capable of increasing islet mass, and is associated with hypoglycemia over the
long term. It can be targeted to the beta cell using standard gene
targeting techniques. Potential exists for beta cell engineering using
this strategy.
Targeted Expression of Placental Lactogen in the Beta Cells of
Transgenic Mice Results in Beta Cell Proliferation, Islet Mass
Augmentation, and Hypoglycemia*
§,,
,,
Division of Endocrinology, University of
Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, the
¶ Yale University Schools of Nursing and Medicine, New Haven,
Connecticut 06520, the Department of Cell Biology and
Neuroanatomy, University of Minnesota School of Medicine, Minneapolis,
Minnesota 55455, and the ** Department of Biology, University of
California, Santa Cruz, California 95064
*
This work was supported by National Institutes of Health
Grants DK 47168, DK 55023, DK 41230, DK 33655, and HD 14966.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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